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Murphy, Aileen, and Thomas N. Garavan. "The Adoption and Diffusion of an NHRD Standard: A Conceptual Framework." Human Resource Development Review 8, no. 1 (February 15, 2009): 3–21. http://dx.doi.org/10.1177/1534484308330019.
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Christofferson, Austin, Sheri Skerget, Jessica Aldrich, Christophe Legendre, Sara Nasser, Jennifer Yesil, Daniel Auclair, The MMRF CoMMpass Network, Sagar Lonial, and Jonathan J. Keats. "Unsupervised Clustering of DNA Copy Number Profiles Identifies a High-Risk Subtype of Hyperdiploid Multiple Myeloma: An Mmrf Commpass Analysis." Blood 134, Supplement_1 (November 13, 2019): 1805. http://dx.doi.org/10.1182/blood-2019-132152.
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Multiple myeloma (MM) is a malignancy of the antibody producing plasma cell, which exhibits a high degree of genetic diversity between patients. As genetic analysis technologies have improved so has our understanding of the diverse genetic phenotypes underlying the disease. The MMRF CoMMpass study (NCT01454297) is using whole genome (WGS), exome (WES), and RNA (RNAseq) sequencing to provide a precise characterization of each patient before and after therapy. However, these advanced assays are not widely available to patients today limiting the utility of many observations to a small population of patients. To expand the utility of the data set to a broader patient population we focused on DNA copy number (CN) phenotypes that can be identified by the standard FISH assays widely used in the field. To discover potential underlying phenotypes of myeloma beyond the known dichotomy of hyperdiploid (HRD) and non-hyperdiploid (NHRD) karyotypes, unsupervised consensus clustering was performed on 871 patients with CN profiles from WGS. Given the limited dynamic range of CN values, a Monte Carlo reference-based consensus clustering algorithm, M3C, was used to limit potential overfitting issues. Three independent replicates of this procedure identified an optimal solution of eight subtypes with no more than 6 patients having different class assignments between replicates. The eight CN subtypes consisted of five HRD and three NHRD subtypes and were annotated based on common CN features. The HRD classic subtype had ubiquitous CN gains, trisomies, of classic HRD chromosomes, 3, 5, 7, 9, 11, 15, and 19. The remaining HRD subtypes were annotated based on deviations from the classic HRD phenotype. The HRD, ++15 subtype phenocopies classic HRD except tetrasomy, not trisomy, is observed on chr15. Two groups of HRD patients were identified lacking CN gains of chr7 which are split into two distinct subtypes: the HRD, diploid 7 subtype, which lacked gains of chr7; and the HRD diploid 3, 7 subtype lacking trisomies of both chr3 and chr7. This suggest some relationship between chromosomes 3 and 7 where trisomy 7 is not tolerated in the absence of trisomy 3. Finally, the HRD, +1q, diploid 11, -13 subtype had gains of the classic HRD chromosomes except chr11 with gains of chr1q and loss of chr13. This subtype suggests trisomy 11 is essential for an HRD phenotype but it can be phenocopied by the combination of 1q gains and 13 loss. Within the NHRD subtypes, the diploid subtype is almost devoid of CN abnormalities less a common gain of 11q initiating at the breakpoint the t(11;14) event, which is almost universally observed in this subtype. Unlike the diploid subtype, the remaining NHRD subtypes have more complex CN profiles with the -13 subtype defined by monosomy 13, and the +1q/-13 subtype defined by gains of 1q and monosomy 13. Outcome analyses of the CN subtypes identified in CoMMpass revealed that both HRD and NHRD patients with gains of chr1q and loss of chr13 exhibited poor PFS and OS outcomes as compared to patients in other CN subtypes. Interestingly, the PFS curves split into three groups with a good risk group defined by the HRD classic and HRD ++15 subtypes. a high-risk group defined by 1q gain and monosomy 13 regardless of ploidy phenotype, and an intermediate group with all other subtypes. The distribution of HRD patients into these three outcome groups highlights the danger of assuming all HRD myeloma patients will have similar outcomes. Patients in the HRD, +1q, diploid 11, -13 subtype exhibited poor OS outcomes (median = 56 months) as compared to patients in the HRD, ++15 (p<0.01), HRD, classic (median = 65 months, p<0.05), diploid (p<0.01), and -13 (p<0.05) subtypes. Patients in the +1q, -13 subtype also exhibited poor OS outcomes (median = 57 months) as compared to patients in the diploid (p<0.01), -13 (p<0.05), HRD classic (p<0.05), and HRD, ++15 (p<0.01) subtypes. Overall, both HRD and NHRD patients with gain of 1q and loss of chr13 exhibit poor outcome as compared to patients with other genetic backgrounds (HR = 1.928, 95% CI = 1.435 - 2.59, p<0.001). Further, the observation that NHRD patients in the +1q, -13 subtype exhibit poor OS outcomes as compared to NHRD patients in the -13 subtype highlights the importance of 1q gains in determining patient prognosis. These results can easily be translated into clinics around the world by matching existing FISH data to each of these groups until more advanced testing is common practice. Disclosures Lonial: BMS: Consultancy; GSK: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy.
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Chamila Kalubowila, Kasunee, D. L. Wanigarathne, P. A. D. D. S. Ponweera, G. K. P. Darshana, and S. S. A. B. M. S. K. Attanayake. "SARS-COV-2 AND TUBERCULOSIS CO-INFECTION: AUDIT ON PATIENT EXPERIENCE ON TREATMENT SERVICES AT THE NATIONAL HOSPITAL FOR RESPIRATORY DISEASES-WELISARA, SRI LANKA." International Journal of Advanced Research 10, no. 03 (March 31, 2022): 805–11. http://dx.doi.org/10.21474/ijar01/14452.
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Background:Patients who are well informed and motivated are more likely to utilize health services, thus, it improves adherence to medication. Hence, this audit aimed to improve the patient experience on treatment services at the National Hospital for Respiratory Diseases (NHRD), Welisara, Sri Lanka. Methods:Patients admitted from 15th August 2021 to 25th February 2022 to the NHRD and diagnosed with COVID-19 and tuberculosis (TB) co-infection were included. Twnety-two (22) process indicators were used and data were collected using a pretested self-administered questionnaire.Sixty-percent of thepatients had a good experience for each service received was the standard. Data were presented as frequency distributions and mean with their standard deviation (SD). Informed written consent was obtained prior to the data collection. Results: Out of 60 patients who were diagnosed with SARS-CoV-2 and TB co-infection, 59 were responded (response rate was 98.3%). A majority were males (n=47, 79.7%) and belonged to 41 to 60 age category (n=29, 49.2%). Ten indicators did not meet the standard. The highest experience was shown in perceived waiting time (mean 86.8, SD ± 8.8) and the lowest experience was shown in perceived time spent with the health care provider (mean 57.9, SD ± 11.8). More than half (n=31, 52.5%) of the patients reported overall good experiences on treatment services. However, age and gender did not show any significant relationship with the good experience of treatment services received (p>0.05). Conclusion: This audit shows the marginally good experience of treatment services received, but highlight areas such as time to discuss with the doctor, instructions on treatment given by the doctor and information given on available services on continuation of TB treatment are needed much improvement even in the pandemic situation.
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Lada, Christina Olly. "Comparing The Anthropometric Measurements of Intra-Extra Uterine Period between Stunting and Non-stunting Children Aged 6-24 Months Old in Bogor Tengah Subdistrict, Bogor City, West Java." World Nutrition Journal 3, no. 1 (August 2, 2019): 1. http://dx.doi.org/10.25220/wnj.v03.i1.0002.
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Introduction: The prevalence of stunting in children under two years old is high in developing country. Stunting in the early of life has many negative health consequences in later life, while the positive view is stunting could be prevent earlier by detecting a predisposing factors in intrauterine and extrauterine periode. Anthropometry of intrauterine predisposing factors (IntraPF) and Extrauterine predisposing factors (ExtraPF) could detect growth retardation. These study aim was to prove that there were significant different of IntraPF and ExtraPF between stunting and non stunting children aged 6-24 months.Methods: This comparative cross sectional study was nested to (Bogor longitudinal study on child growth and development (BLSCGD) held by National Health Research and Development (NHRD), Health Ministry of Indonesia. Subjects who defined as stunting if their height for age was more than two standard deviations below the WHO Child Growth standards median. There were 38 stunting and 46 non-stunting aged 6-24 months who met the study criteria. Independent variable was (1)IntraPF follow as maternal height, weight and length of neonatal, (2)ExtraPF: weight gain and body length gain at first six months of neonatal. Primary and secondary data collection was carried out from July 2017 to Februari 2018, held at the BLSCGD. All of body measurement using WHO standard. Appropriate statistical analysis was used to compare the stunting and non-stunting groups with a significance limit of p <0.05.Results: Statistical analysis tests showed that: significantly different and lower IntraPF in the stunting group was maternal height, birth weight and length of the subjects compare to non-stunting and there were significant different and lower of ExtraPF follow as weight gain in the first six months, average weight gain per month in the first six months, increase in body length in the first six months, average increase in body length every month in the first six monthssignificantly lower in stunting children compare to non stunting children.Conclusion: The antropometric of intrauterine, extrauterine predisposing factors have been showed to have an impact on the child's height. It is important to monitor the anthropometry of the mother before pregnancy and provide nutritional interventions in the first 1000 days
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Friedman, Allon N., Andrew G. Bostom, Andrew S. Levey, Irwin H. Rosenberg, Jacob Selhub, and Andreas Pierratos. "Plasma Total Homocysteine Levels among Patients Undergoing Nocturnal versus Standard Hemodialysis." Journal of the American Society of Nephrology 13, no. 1 (January 2002): 265–68. http://dx.doi.org/10.1681/asn.v131265.
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ABSTRACT. Mild hyperhomocysteinemia, a putative risk factor for arteriosclerotic outcomes, is seen in >85% of hemodialysis patients. Therapeutic strategies, including pharmacologic-dose B vitamin supplementation and “high-flux” or “super-flux” hemodialysis, have consistently failed to normalize total homocysteine (tHcy) levels in these patients. Predialysis plasma tHcy levels in 23 patients who were undergoing nocturnal hemodialysis (NHD) six or seven nights/wk were compared with those in 31 patients from the same Canadian dialysis unit who were undergoing chronic standard hemodialysis (SHD) (all <65 yr of age, undergoing thrice-weekly treatments). The SHD patients were similar to typical North American chronic hemodialysis patients with respect to B vitamin status and albumin, creatinine, and tHcy levels. Geometric mean tHcy levels for the NHD patients were significantly lower (12.7 versus 20.0 μM, P < 0.0001), as was the prevalence of mild-to-moderate hyperhomocysteinemia (>12 μM; NHD, 57%; SHD, 94%; P = 0.002). Analysis of covariance adjusted for plasma folate, vitamin B12, and pyridoxal 5′-phosphate levels, age, and gender confirmed that NHD was independently associated with 6.0 μM lower geometric mean tHcy levels (P = 0.001). It is concluded that tHcy levels are significantly lower among NHD patients, compared with SHD patients. Clinical trials will be necessary to confirm that NHD is effective in reducing tHcy levels among patients with dialysis-dependent end-stage renal disease.
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Murray, Cliodhna E., Andreas Fuchs, Heide Grünewald, Owen Godkin, Norbert P. Südkamp, and Lukas Konstantinidis. "Identifying Disparities in the Management of Hip Fractures Within Europe: A Comparison of 3 Health-Care Systems." Geriatric Orthopaedic Surgery & Rehabilitation 10 (January 1, 2019): 215145931987294. http://dx.doi.org/10.1177/2151459319872941.
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Introduction: This study investigates the management of hip fractures in a German maximum care hospital and compares these data to evidence-based standard and practice in 180 hospitals participating in the UK National Hip Fracture Database (NHFD) and 16 hospitals participating in the Irish Hip Fracture Database (IHFD). This is the first study directly comparing the management of hip fractures between 3 separate health-care systems within Europe. Methods: Electronic medical data were collected retrospectively describing the care pathway of elderly patients with a hip fracture admitted to a large trauma unit in the south of Germany “University Hospital Freiburg” (UHF). The audit evaluated demographics, postoperative outcome, and the adherence to the 6 “Blue Book” standards of care. These data were directly compared with the data from the UK NHFD and the IHFD acquired from 180 and 16 hospitals, respectively. Results: At 36 hours, 95.8% of patients had received surgery in UHF, compared to 71.5% in the NHFD and 58% of patients in the IHFD. The rate of in-hospital mortality was 4.7% compared to 7.1% in the NHFD and 5% in the IHFD. The mean average acute length of stay was 13.4 days compared to 16.4 days in the NHFD and 20 days in the IHFD. Reoperation rates are 3.3% compared to 1% in the NHFD and 1.1% in the IHFD; 50.5% of patients were discharged on bone protection medication, compared to 47% in the IHFD and 79.3% in the UK NHFD. Discussion: Despite uniformly acknowledged evidence-based treatment guidelines, the management of hip fractures remains heterogeneous within Europe. Conclusion: These data show that different areas of the hip fracture care pathway in Germany, England, and Ireland, respectively, show room for improvement in light of the growing socioeconomic burden these countries are expected to face.
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De Vleeschauwer, S., D. Van Raemdonck, B. Vanaudenaerde, R. Vos, and G. Verleden. "108: NHBD Meet the Standard of HBD Regarding Early Outcome after LTx." Journal of Heart and Lung Transplantation 28, no. 2 (February 2009): S103. http://dx.doi.org/10.1016/j.healun.2008.11.786.
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Evans, Carolyn. "HUMAN RIGHTS COMMISSIONS AND RELIGIOUS CONFLICT IN THE ASIA-PACIFIC REGION." International and Comparative Law Quarterly 53, no. 3 (July 2004): 713–29. http://dx.doi.org/10.1093/iclq/53.3.713.
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The last decade has seen the rise of a potentially significant development in the Asia-Pacific region in regard to human rights—the establishment of National Human Rights Institutions (particularly Human Rights Commissions) in numerous States.2 National Human Rights Commissions (hereafter NHRC) established in compliance with United Nations standards have been established in Australia, Fiji, India, Indonesia, Malaysia, Mongolia, Nepal, New Zealand, Philippines, Republic of Korea, Sri Lanka, and Thailand.3 In many of these States, however, human rights abuses are still widespread and serious. The establishment of NHRC, which generally do not have the power to make enforceable decisions, could easily be derided as an attempt by governments to create a fac.ade of respect for human rights while failing to take the enforcement of those rights seriously.4 While this criticism has a degree of validity, NHRC have played a constructive, if limited role, in the promotion and protection of human rights in the Asia-Pacific region.
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Ghimire, N., A. Panthee, M. R. Sharma, R. K. Adhikari, and P. Gyanwali. "Research during COVID-19 Pandemic: Perspectives from the Ethics Committees of a Lower Middle Income Country." Kathmandu University Medical Journal 18, no. 4 (December 31, 2020): 420–22. http://dx.doi.org/10.3126/kumj.v18i4.49257.
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The pandemic of Coronavirus Disease 2019 (COVID-19) has created paradoxically a good opportunity globally to conduct research in the field of health and social science, and a Lower Middle-Income Country (LMIC) like Nepal is not an exception in this regard. During this ongoing pandemic, the Ethical Review Board (ERB) of Nepal Health Research Council (NHRC) has received numerous research proposals regarding COVID-19. As its main responsibility is to ensure participants’ safety, at the same time maintaining the scientific standard of research, the ERB has meticulously gone through all the proposals received so far. During this situation of a health emergency, the ERB of NHRC has had a different experience compared to the usual time. Its strength, weakness, opportunities, and threats have been like never before.
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Hilal, Tarek, Vera Puetter, Christiane Otto, Karsten Parczyk, and Benjamin Bader. "A Dual Estrogen Receptor TR-FRET Assay for Simultaneous Measurement of Steroid Site Binding and Coactivator Recruitment." Journal of Biomolecular Screening 15, no. 3 (February 11, 2010): 268–78. http://dx.doi.org/10.1177/1087057109359196.
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The human estrogen receptors (hER) are members of the nuclear hormone receptor (NHR) superfamily and represent important drug targets for the pharmaceutical industry. Initially, ligand binding assays were used to identify novel ligands using receptors purified from native tissues. With the advent of molecular cloning techniques, cell-based transactivation assays have been the gold standard for many years of drug discovery. With the elucidation of the structural mechanisms underlying the activation of NHRs, cell-free assays with purified receptors have become important tools to directly assess different binding sites (e.g., the hormone binding site or the cofactor binding site). The available cell-free assays have so far facilitated the study of one binding site at a time. With the introduction of Terbium (Tb3+)–based time-resolved fluorescence energy transfer (TR-FRET), it has become possible to measure 2 different interactions within 1 test tube in parallel. The authors have applied this technology to develop a dual readout system for the simultaneous monitoring of steroid hormone site binding and cofactor peptide recruitment. They took advantage of a commercially available fluorescent tracer as an indicator for classical steroid site binding and designed a novel peptide derived from the peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1a) as an indicator for functional agonistic behavior of a test compound. The established assay is able to differentiate between agonists, antagonists, partial agonists, and compounds binding to the cofactor recruitment site. The IC50 values obtained for a number of reference compounds in the multiplexed assay are in concordance with published data. The simple 1-step mix-and-measure protocol gives excellent quality and robustness and can be miniaturized to 5-µL volume.
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Keating, Anthony. "Setting the Agenda for the Press: The 1929 Case Against the Waterford Standard." New Hibernia Review 16, no. 2 (2012): 17–32. http://dx.doi.org/10.1353/nhr.2012.0019.
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Lee, John Sanghyun. "Discrimination Standard based on Sexual Orientation under National Human Right Commission(NHRC) Act with respect to Autonomy and Freedom to Religious Education of Religious University — Analyzing NHRC Decisions —." Yonsei Law Review 29, no. 1 (March 31, 2019): 1–36. http://dx.doi.org/10.21717/ylr.29.1.1.
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Keser, Irena, Selma Cvijetić, Ana Ilić, Irena Colić Barić, Dario Boschiero, and Jasminka Z. Ilich. "Assessment of Body Composition and Dietary Intake in Nursing-Home Residents: Could Lessons Learned from the COVID-19 Pandemic Be Used to Prevent Future Casualties in Older Individuals?" Nutrients 13, no. 5 (April 29, 2021): 1510. http://dx.doi.org/10.3390/nu13051510.
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The population of older adults, especially those living in the nursing homes, is growing. The sedentary lifestyle and possible poor nutrition in nursing homes place residents (NHRs) at risk for body composition impairments, malnutrition, and, subsequently, numerous chronic diseases. The aim of this study was to assess body composition (including body fluids) and dietary intake in NHRs. The association between osteosarcopenic adiposity syndrome (OSA) and its components, osteopenic adiposity (OA), sarcopenic adiposity (SA), and adiposity-only (AD), and specific macro- and micro-nutrients was evaluated as well. The study included 84 participants (82.1% women), aged 65.3–95.2 years. Body composition was assessed with an advanced bioelectrical impedance device BIA-ACC® and dietary intake was assessed via 24-h recall and analyzed using “Nutrition” software. The majority (95%) of participants were overweight with a high body fat and low muscle and bone mass, leading to a high prevalence of OSA (>50%), OA (13%), and AD (26%). There were only a few participants with SA, and they were not analyzed. The highest extracellular water/total body water ratio was observed in the OSA participants, indicating a heightened inflammatory state. Participants in all three body composition categories had a similar nutrient intake, with protein, fiber, omega-3 fatty acids, and almost all micronutrients being far below recommendations. In conclusion, a high prevalence of OSA among NHRs accompanied by a poor dietary intake, could place these residents at a very high risk for COVID-19 infections. Therefore, optimization of body composition and nutritional status should be included along with standard medical care in order to provide better health maintenance, particularly in the COVID-19 era.
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Johansen, Antony, Christopher Boulton, Karen Hertz, Michael Ellis, Vivienne Burgon, Sunil Rai, and Rob Wakeman. "The National Hip Fracture Database (NHFD) – Using a national clinical audit to raise standards of nursing care." International Journal of Orthopaedic and Trauma Nursing 26 (August 2017): 3–6. http://dx.doi.org/10.1016/j.ijotn.2017.01.001.
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Sandelin, Albin, and Wyeth W. Wasserman. "Prediction of Nuclear Hormone Receptor Response Elements." Molecular Endocrinology 19, no. 3 (March 1, 2005): 595–606. http://dx.doi.org/10.1210/me.2004-0101.
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Abstract The nuclear receptor (NR) class of transcription factors controls critical regulatory events in key developmental processes, homeostasis maintenance, and medically important diseases and conditions. Identification of the members of a regulon controlled by a NR could provide an accelerated understanding of development and disease. New bioinformatics methods for the analysis of regulatory sequences are required to address the complex properties associated with known regulatory elements targeted by the receptors because the standard methods for binding site prediction fail to reflect the diverse target site configurations. We have constructed a flexible Hidden Markov Model framework capable of predicting NHR binding sites. The model allows for variable spacing and orientation of half-sites. In a genome-scale analysis enabled by the model, we show that NRs in Fugu rubripes have a significant cross-regulatory potential. The model is implemented in a web interface, freely available for academic researchers, available at http://mordor.cgb.ki.se/NHR-scan.
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Pulst, Alexandra, Alexander Maximilian Fassmer, Falk Hoffmann, and Guido Schmiemann. "Paramedics’ Perspectives on the Hospital Transfers of Nursing Home Residents—A Qualitative Focus Group Study." International Journal of Environmental Research and Public Health 17, no. 11 (May 26, 2020): 3778. http://dx.doi.org/10.3390/ijerph17113778.
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Emergency department (ED) visits and hospital admissions are common among nursing home residents (NHRs). Little is known about the perspectives of emergency medical services (EMS) which are responsible for hospital transports. The aim of this study was to explore paramedics’ experiences with transfers from nursing homes (NHs) and their ideas for possible interventions that can reduce transfers. We conducted three focus groups following a semi-structured question guide. The data were analyzed by content analysis using the software MAXQDA. In total, 18 paramedics (mean age: 33 years, male n = 14) participated in the study. Paramedics are faced with complex issues when transporting NHRs to hospital. They mainly reported on structural reasons (e.g., understaffing or lacking availability of physicians), which led to the initiation of an emergency call. Handovers were perceived as poorly organized because required transfer information (e.g., medication lists, advance directives (ADs)) were incomplete or nursing staff was insufficiently prepared. Hospital transfers were considered as (potentially) avoidable in case of urinary catheter complications, exsiccosis/infections and falls. Legal uncertainties among all involved professional groups (nurses, physicians, dispatchers, and paramedics) seemed to be a relevant trigger for hospital transfers. In paramedics’ point of view, emergency standards in NHs, trainings for nursing staff, the improvement of working conditions and legal conditions can reduce potentially avoidable hospital transfers from NHs.
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Lai, Chi-Wan. "Experiences of Accreditation of Medical Education in Taiwan." Journal of Educational Evaluation for Health Professions 6 (December 20, 2009): 2. http://dx.doi.org/10.3352/jeehp.2009.6.2.
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This review aims to introduce the Taiwanese Medical Accreditation System: its history, role and future goals. In 1999, the Ministry of Education, Taiwanese Government commissioned the non-profit National Health Research Institutes (NHRI) to develop a new medical accreditation system. According to that policy, the Taiwan Medical Accreditation Council (TMAC) was established in the same year. The council serves a similar function to that of the Liaison Committee on Medical Education (LCME) of the United States and the Australian Medical Council (AMC). The accreditation process consists of a self-assessment plus a four-day site visit by a team of eight medical educators that are headed by one of the council members of the TMAC. The first cycle of initial visits was completed from 2001 to 2004. Subsequent follow-up visits were arranged according to the results of the survey with smaller-sized teams and shorter periods. There is evidence to suggest that the majority (seven of eleven) of the medical schools in Taiwan have made good progress. TMAC?占퐏 next step will be to monitor the progress and raise the standard of medical education in individual schools with a homogenous, superior standard of medical education.
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Rafid, Raihan Rahman. "Human Rights During the Pandemic and the National Human Rights Commission of Bangladesh." Asia-Pacific Journal on Human Rights and the Law 23, no. 3 (November 16, 2022): 315–53. http://dx.doi.org/10.1163/15718158-23030002.
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Abstract The covid-19 outbreak has brought forth the existing cracks and crevices in the governance of Bangladesh. At such a time, the National Human Rights Commission of Bangladesh (nhrcb), as the only State institution mandated to protect and promote human rights exclusively and impartially, is tasked with a crucial role to ensure respect for human rights. This article assesses the activities undertaken by the nhrcb during the pandemic and finds that the nhrcb evinced only a limited role in monitoring the violation of rights and provided formulaic recommendations to the government. It did not observe the implementation of their recommendations and has performed rather formalistically. While the country has experienced a deteriorating human rights situation, the nhrcb has failed to flex its muscles when compared to other national human rights institutions in South Asia. This article argues that the national human rights institutions (nhri s) in India, Nepal and Sri Lanka, embedded in a similar context and armed with almost identical mandates, have demonstrated a novel and strenuous effort intending to adapt to and fulfil their functions during the unprecedented crisis. The nhrcb may benefit by learning from these nhri s as well as taking lessons from its own past activities. Previously, it did not eschew politically sensitive issues and earmarked a strong leadership even with limited institutional capacities. The nhrcb has however responded to the changing dynamics and challenges posed by the covid-19 pandemic with silence. It needs to become more vibrant to enhance, regionally and internationally, the country’s image in upholding human rights norms and standards.
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Veronesi, Gianluca, Kirsten Harley, Paul Dugdale, and Stephanie D. Short. "Governance, transparency and alignment in the Council of Australian Governments (COAG) 2011 National Health Reform Agreement." Australian Health Review 38, no. 3 (2014): 288. http://dx.doi.org/10.1071/ah13078.
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Objective This article provides a policy analysis of the Australian government’s National Health Reform Agreement (NHRA) by bringing to the foreground the governance arrangements underpinning the two arms of the national reforms, to primary health care and hospital services. Methods The article analyses the NHRA document and mandate, and contextualises the changes introduced vis-à-vis the complex characteristics of the Australian health care system. Specifically, it discusses the coherence of the agreement and its underlying objectives, and the consistency and logic of the governance arrangements introduced. Results The policy analysis highlights the rationalisation of the responsibilities between the Commonwealth and states and territories, the commitment towards a funding arrangement based on uniform measures of performance and the troubled emergence of a more decentralised nation-wide homogenisation of governance arrangements, plus efforts to improve transparency, accountability and statutory support to increase the standards of quality of care and safety. Conclusions It is suggested that the NHRA falls short of adequately supporting integration between primary, secondary and tertiary health care provision and facilitating greater integration in chronic disease management in primary care. Successfully addressing this will unlock further value from the reforms. What is known about the topic? The Council of Australian Governments (COAG) 2011 health reforms have introduced governance structures and transparency mechanisms that are unprecedented in the Australian context. There is still a gap in knowledge and overall understanding in relation to their significance and how they will fare given the complex characteristics of the Australian health system. What does this paper add? This article discusses the positive changes introduced, such as the rationalisation of the relationships between the Commonwealth and states and territories, the introduction of more transparent funding arrangements, the provision of unified governance templates and the potential gains in reducing waiting lists. It also highlights the most glaring shortcoming of the health reforms, which is the missed opportunity to strengthen integration between primary, secondary and tertiary care providers. What are the implications for practitioners? More effective integration between care providers appears to be one of the greatest challenges ahead. Further changes are needed to make the primary care and secondary and tertiary arms of the health system work together more effectively. Moreover, general practice needs to be brought into a closer working relationship with non-medical primary health and community care to tackle the growing burden of chronic disease.
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Lulu, Jorge, Paulo Cesar Sentelhas, Mário José Pedro Júnior, José Ricardo Macedo Pezzopane, and Gabriel Constantino Blain. "Estimating leaf wetness duration over turfgrass, and in a 'Niagara Rosada' vineyard, in a subtropical environment." Scientia Agricola 65, spe (December 2008): 10–17. http://dx.doi.org/10.1590/s0103-90162008000700004.
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Leaf wetness duration (LWD) is a key parameter in agrometeorology because it is related to plant disease occurrence. As LWD is seldomly measured in a standard weather station it must be estimated to run warning systems for schedule chemical disease control. The objective of the present study was to estimate LWD over turfgrass considering different models with data from a standard weather station, and to evaluate the correlation between estimated LWD over turfgrass and LWD measured in a 'Niagara Rosada' vineyard, cultivated in a hedgerow training system, in Jundiaí, São Paulo State, Brazil. The wetness sensors inside the vineyard were located at the top of the plants, deployed at an inclination angle of 45º and oriented southwest, with three replications. The methods used to estimate LWD were: number of hours with relative humidity above 90% (NHRH > 90%), dew point depression (DPD), classification and regression tree (CART) and Penman-Monteith (PM). The CART model had the best performance to estimate LWD over turfgrass, with a good precision (R² = 0.82) and a high accuracy (d = 0.94), resulting in a good confidence index (c = 0.85). The results from this model also presented a good correlation with measured LWD inside the vineyard, with a good precision (R² = 0.87) and a high accuracy (d = 0.96), resulting in a high confidence index (c = 0.93), showing that LWD in a 'Niagara Rosada' vineyard can be estimated with data from a standard weather station.
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Cocchieri, Riccardo, Bertus van de Wetering, Sjoerd van Tuijl, Iman Mousavi, Robert Riezebos, and Bastian de Mol. "At the Crossroads of Minimally Invasive Mitral Valve Surgery—Benching Single Hospital Experience to a National Registry: A Plea for Risk Management Technology." Journal of Cardiovascular Development and Disease 9, no. 8 (August 11, 2022): 261. http://dx.doi.org/10.3390/jcdd9080261.
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Almost 30 years after the first endoscopic mitral valve repair, Minimally Invasive Mitral Valve Surgery (MIMVS) has become the standard at many institutions due to optimal clinical results and fast recovery. The question that arises is can already good results be further improved by an Institutional Risk Management Performance (IRMP) system in decreasing risks in minimally invasive mitral valve surgery (MIMVS)? As of yet, there are no reports on IRMP and learning systems in the literature. (2) Methods: We described and appraised our five-year single institutional experience with MIMVS in isolated valve surgery included in the Netherlands Heart Registry (NHR) and investigated root causes of high-impact complications. (3) Results: The 120-day and 12-month mortality were 1.1% and 1.9%, respectively, compared to the average of 4.3% and 5.3% reported in the NHR. The regurgitation rate was 1.4% compared to 5.2% nationwide. The few high-impact complications appeared not to be preventable. (4) Discussion: In MIMVS, freedom from major and minor complications is a strong indicator of an effective IRMP but remains concealed from physicians and patients, despite its relevance to shared decision making. Innovation adds to the complexity of MIMVS and challenges surgical competence. An IRMP system may detect and control new risks earlier. (5) Conclusion: An IRMP system contributes to an effective reduction of risks, pain and discomfort; provides relevant input for shared decision making; and warrants the safe introduction of new technology. Crossroads conclusions: investment in machine learning and AI for an effective IRMP system is recommended and the roles for commanding and operating surgeons should be considered.
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Chiang, I.-Jen, Wen-Yi Shau, Wei-Tse Fang, Chi-Hui Fang, and Yen-Yang Chen. "Targeted therapy in gastrointestinal stromal tumor (GIST): A nationwide database analysis from Taiwan." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 437. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.437.
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437 Background: Gastrointestinal stromal tumor (GIST) is a visceral sarcoma that arises from the gastrointestinal tract. Currently, imatinib (first-line) and sunitinib (second-line) are two reimbursed targeted therapies for GIST in Taiwan. This study aimed to evaluate the real world data of targeted therapies in GIST treatment among Taiwanese population. Methods: We conducted a nationwide retrospective cohort study based on data from the National Health Insurance Research Database (NHIRD) between January 2005 and December 2010. NHIRD is a comprehensive database of administrative and claim data which covers over 99% of entire population in Taiwan. Patients were selected with ICD codes and targeted therapy utilization, imatinib (IMA) or sunitinib (SUN). Time to treatment discontinuation (DC) due to any reasons (such as death, intolerance and disease progression) was estimated using Kaplan-Meier analysis. Results: From 2005 to 2010, the incidence rate of GIST in Taiwan was between 20 and 30 cases per million. A total of 3,436 GIST patients were identified; the mean age was 63.2 years and 57 % were male. Most patients (94.7%) received standard dose IMA (…400mg/day). Among these patients, 136 patients (4.0%) required IMA dose escalation and 44 (1.3%) patients switched to SUN after IMA. The probability of the 1st-line treatment DC was 20%, 30.7%, 38.9%, 43.2%, and 47.1% for years 1 to 5, respectively. The probability of a change in treatment pattern (defined as either IMA dose escalation or switch to SUN) was 4% 6.8%, 9.6%, 10.5% and 11.7% for years 1 to 5. Lastly, the probability of the 2nd-line treatment DC was 20.5%, 33.7%, 41.1%, 44.8%, 51.7% for years 1 to 5, respectively. Conclusions: First-line IMA plus other treatment modalities may provide additional benefits to progression-free survival. Taiwanese GIST patients who failed first-line treatment still gained benefit from either IMA dose escalation or a switch to SUN. Additional analysis is required for the detailed comparison in different treatment patterns.
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Chen, Wei-Cheng, Jian-Ri Li, Shian-Shiang Wang, Chuan-Shu Chen, Chen-Li Cheng, Sheng-Chun Hung, Ching-Heng Lin, Kun-Yuan Chiu, and Po-Chi Liao. "Conventional androgen deprivation therapy is associated with an increased risk of fracture in advanced prostate cancer, a nationwide population-based study." PLOS ONE 18, no. 1 (January 4, 2023): e0279981. http://dx.doi.org/10.1371/journal.pone.0279981.
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Purpose Androgen deprivation therapy (ADT) is the standard of care in advanced prostate cancer. We conducted a Taiwan National Health Insurance Research Database (NHIRD) study to evaluate the association between ADT and fracture risk in patient with prostate cancer in Taiwan. Methods Between 2001 and 2008, data from the Taiwan NHIRD was collected. We separated newly diagnosed prostate cancer patients into four groups: the injection of gonadotropin-releasing hormone agonists and antagonists group, the orchiectomy group, the oral antiandorgens group and the radical prostatectomy only group. A non-cancer matched control group was also assigned for comparison. T tests, chi-squared tests, multivariate Cox proportional hazard regression were performed. A subsequent fracture event was defined according to the appropriate diagnosis codes (ICD9-CM 800–829) with hospitalization. Patients with fracture before their diagnosis with prostate cancer were excluded. Results Overall, 22517 newly diagnosed patients with prostate cancer were enrolled in the study. After exclusion criteria were applied, 13321 patients were separated into the injection group (5020 subjects), the orchiectomy group (1193 subjects), the oral group (6059 subjects) and the radical prostatectomy only group (1049 subjects). The mean age of the overall study population was 74.4 years. Multi-variant analysis disclosed a significantly increased risk of fracture in the injection group, the orchiectomy group, and the oral group (hazard ratio [HR] = 1.55, 95%, confidence interval [CI] 1.36 to 1.76, p<0.001, HR = 1.95, 95%, CI 1.61 to 2.37, p<0.001, HR = 1.37, 95%, CI 1.22 to 1.53, p<0.001, respectively). In contrast, a significantly decreased fracture risk was noted in the radical prostatectomy only group (HR = 0.51, 95%, CI 0.35 to 0.74, p = 0.001). Patients receiving osteoporosis medication had a significantly decreased fracture risk (HR = 0.26, 95%, CI 0.19–0.37, p<0.001). Conclusions ADT is associated with an increased risk of fracture. For patients receiving long-term prostate cancer castration therapy, doctors should always keep this complication in mind and arrange proper monitoring and provide timely osteoporosis medication.
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Mallows, Colin, and Larry Shepp. "The Necklace Process." Journal of Applied Probability 45, no. 1 (March 2008): 271–78. http://dx.doi.org/10.1239/jap/1208358967.
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Start with a necklace consisting of one white bead and one black bead, and add new beads one at a time by inserting each new bead between a randomly chosen adjacent pair of old beads, with the proviso that the new bead will be white if and only if both beads of the adjacent pair are black. Let Wn denote the number of white beads when the total number of beads is n. We show that EWn = n/3 and, with c2 = 2/45, that (Wn − n/3) / c√n is asymptotically standard normal. We find that, for all r ≥ 1 and n > 2r, the rth cumulant of the distribution of Wn is of the form nhr. We find the expected numbers of gaps of given length between white beads, and examine the asymptotics of the longest gaps.
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Brahmbhatt, Yasmin, Arinze Ikeme, Navjyot Bhogal, and Vincenzo Berghella. "Successful Pregnancy Using the NxStage Home Hemodialysis System." Case Reports in Nephrology 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/1358625.
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Pregnancy in the setting of the uremic milieu of renal disease has a lower success rate than in the normal population and is a rare event. While intensified renal replacement therapy (RRT) during pregnancy can lead to improved outcomes, most studies have focused on nocturnal hemodialysis as the main RRT in pregnancy. Although thousands of patients use the home NxStage System One short daily hemodialysis (SDHD) machine in the United States, pregnancy outcomes with this therapy are unknown. The NxStage System One uses low-volume dialysate and hence small and middle molecule clearance may differ compared to conventional therapies and affect pregnancy outcomes. We report a case of a successful conception and pregnancy using the home NxStage system. The NxStage system may provide an alternative to the more routinely used NHD or standard SDHD therapies for women of childbearing age.
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Mudiganty, Srikanth, Ilias Kosmidis, and John Edwin. "Fractured Neck of Femur Management at a District General Hospital: Adherence to NICE guidelines CG124 for total hip replacement." SICOT-J 6 (2020): 46. http://dx.doi.org/10.1051/sicotj/2020045.
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Introduction: The National Institute for Health and Care Excellence (NICE) in 2011 declared standards in the management of fracture neck of femur (NOF) patients suggesting a total hip replacement (THR) if necessary criteria were met. The Best Practice Tariff (BPT) states all NOF fracture patients should be operated on within 36 h of presentation to Accident & Emergency. We conducted this retrospective study for the years 2016–2018 to evaluate the adherence to these guidelines by Basildon and Thurrock University Hospital and compared the results with national standards. Methods: Data for the period from 2016 to 2018 was collected from the National Hip Fracture Database (NHFD) retrospectively. The data was analysed to calculate various procedures performed for fracture NOF fixations, the number of THR’s for displaced intracapsular fracture NOF, and percentage of patients operated within 36 h and evaluated reasons for the delay. Results: Over the 3 years, the number of THR eligible displaced intracapsular neck of femur fracture patients that underwent THR was above the national average. Across all 3 years, the number of patients who underwent surgery within 36 h was less than the national average. Administrative/logistic reasons for the delay were the major cause for delayed surgery in all 3 years. Conclusion: Compliance with the NICE guidelines and achievement of national standards in NOF fracture care is achievable by most district general hospitals. Awareness and implementation of NICE guidelines for THRs need to be enhanced. A sustained, continual team effort and strict vigilance are necessary to prevent delayed surgery.
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Kingwara, Leonard, Muthoni Karanja, Catherine Ngugi, Geoffrey Kangogo, Kipkerich Bera, Maureen Kimani, Nancy Bowen, Dorcus Abuya, Violet Oramisi, and Irene Mukui. "From Sequence Data to Patient Result: A Solution for HIV Drug Resistance Genotyping With Exatype, End to End Software for Pol-HIV-1 Sanger Based Sequence Analysis and Patient HIV Drug Resistance Result Generation." Journal of the International Association of Providers of AIDS Care (JIAPAC) 19 (January 1, 2020): 232595822096268. http://dx.doi.org/10.1177/2325958220962687.
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Introduction: With the rapid scale-up of antiretroviral therapy (ART) to treat HIV infection, there are ongoing concerns regarding probable emergence and transmission of HIV drug resistance (HIVDR) mutations. This scale-up has to lead to an increased need for routine HIVDR testing to inform the clinical decision on a regimen switch. Although the majority of wet laboratory processes are standardized, slow, labor-intensive data transfer and subjective manual sequence interpretation steps are still required to finalize and release patient results. We thus set out to validate the applicability of a software package to generate HIVDR patient results from raw sequence data independently. Methods: We assessed the performance characteristics of Hyrax Bioscience’s Exatype (a sequence data to patient result, fully automated sequence analysis software, which consolidates RECall, MEGA X and the Stanford HIV database) against the standard method (RECall and Stanford database). Exatype is a web-based HIV Drug resistance bioinformatic pipeline available at sanger. exatype.com . To validate the exatype, we used a test set of 135 remnant HIV viral load samples at the National HIV Reference Laboratory (NHRL). Result: We analyzed, and successfully generated results of 126 sequences out of 135 specimens by both Standard and Exatype software. Result production using Exatype required minimal hands-on time in comparison to the Standard (6 computation-hours using the standard method versus 1.5 Exatype computation-hours). Concordance between the 2 systems was 99.8% for 311,227 bases compared. 99.7% of the 0.2% discordant bases, were attributed to nucleotide mixtures as a result of the sequence editing in Recall. Both methods identified similar (99.1%) critical antiretroviral resistance-associated mutations resulting in a 99.2% concordance of resistance susceptibility interpretations. The Base-calling comparison between the 2 methods had Cohen’s kappa (0.97 to 0.99), implying an almost perfect agreement with minimal base calling variation. On a predefined dataset, RECall editing displayed the highest probability to score mixtures accurately 1 vs. 0.71 and the lowest chance to inaccurately assign mixtures to pure nucleotides (0.002–0.0008). This advantage is attributable to the manual sequence editing in RECall. Conclusion: The reduction in hands-on time needed is a benefit when using the Exatype HIV DR sequence analysis platform and result generation tool. There is a minimal difference in base calling between Exatype and standard methods. Although the discrepancy has minimal impact on drug resistance interpretation, allowance of sequence editing in Exatype as RECall can significantly improve its performance.
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Silver, Richard T., Katherine Vandris, Joshua J. Goldman, Fernando Adriano, Y. Lynn Wang, Amy V. Jones, Paul J. Christos, and N. C. P. Cross. "Decrease in JAK2V617F Allele Burden is Not a Prerequisite to Clinical Response in Patients with Polycythemia Vera (PV)." Blood 114, no. 22 (November 20, 2009): 1908. http://dx.doi.org/10.1182/blood.v114.22.1908.1908.
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Abstract Abstract 1908 Poster Board I-931 Previous studies of patients (pts) with polycythemia vera (PV) treated with pegylated interferon (peg-IFNá-2a) have shown an 83% complete hematologic response associated with an 89% molecular response over a median of 11 months (Kiladjian et al. Blood. 2008. 112(8):3065-3072) implying a causative relationship between molecular and hematologic responses. Our data show pts treated with rIFNá-2b or non-rIFNá-2b agents achieve hematologic response despite the absence of a molecular response suggesting that a molecular change is not a prerequisite to hematologic response. Thirty pts diagnosed with PV by the criteria of the Polycythemia Vera Study Group (PVSG) were followed clinically and hematologically with serial quantified JAK2V617F allele burden determined at six-month intervals over a mean of 21.6 months (mos) (range: 6.0 – 56.4 mos). These pts were treated with rIFNá-2b ranging from 0.5 mu to 3.0 mu three times per week depending upon clinical response. Primary clinical endpoints were hematocrit (hct) ≤45% men, ≤42% women, and no need for phlebotomy (PHL). Molecular and hematologic responses were graded according to the criteria of Barosi et al. (Blood. 2009. 113(20):4829-4833): complete hematologic response (CHR: hct ≤45% without PHL, platelets '400×109/L, WBC ≤10×109/L, normal spleen size, asymptomatic); partial hematologic response (PHR: hct ≤45% without PHL or response in 3 or more of the CHR categories); no hematologic response (NHR: failure to meet the criteria of CHR or PHR); complete molecular response (CMR: reduction of JAK2V617F marker to undetectable levels); partial molecular response (PMR: ≥50% reduction in pts with '50% mutant allele burden at baseline, or ≥25% reduction in pts with >50% mutant allele burden at baseline; applicable only to pts with ≥10% baseline allele burden); and no molecular response (NMR: failure to meet the criteria of CMR or PMR). Of the 30 pts treated with rIFNá-2b, 14 had a CHR, 13 had a PHR and 3 had NHR. Of 14 pts who had a CHR, 4 had a PMR and 10 had NMR. Of thirteen pts who had a PHR, 1 had a PMR and 12 had NMR. All 3 pts who had NHR also had NMR. Based on these data, the statistical agreement between hematologic response and molecular response was poor (kappa coefficient = 0.06, P=0.17). We then examined the hematologic responses (HR: CHR+PHR) of 25 non-rIFNá-2b treated pts, which included PHL ± anagrelide (3 pts: 2 HR/NMR, 1 NHR/NMR), dasatinib (5 pts: 5 HR/NMR), imatinib (9 pts: 3 HR/PMR, 4 HR/NMR, 2 NHR/NMR), and hydroxyurea (8 pts: 1 CHR/PMR, 7 HR/NMR). The minimal molecular response to dasatinib and hydroxyurea is noteworthy. Likewise, there was poor statistical agreement between hematologic response and molecular response for non-rIFNá-2b treated patients (kappa coefficient = 0.05, P=0.21). Of all 55 pts (rIFNá-2b and non-rIFNá-2b), those 9 patients with a PMR had a hematologic response (7 CHR and 2 PHR). Of 46 NMR's, 40 pts (87%) had a hematologic response (16 CHR, 24 PHR). Thus, NMR did not exclude the possibility of achieving CHR. Regardless of therapy, we demonstrate poor agreement between hematologic and molecular responses for these drugs (all pts: kappa = 0.05, P=0.13). This suggests a difference in action between peg-IFNá-2a, shown to cause molecular and hematologic responses concurrently, and several drugs we examined leading to clinical response without necessarily changing JAK2V617F allele burden. In this regard, other parameters such as bone marrow morphology and new biological markers may be useful in reconciling the differences. In summary, we find that a hematologic response is not always accompanied by a molecular response in PV pts treated with either rIFNá-2b or some non-rIFNá-2b drugs. We thus conclude that a reduction in JAK2V617F allele burden is not always required for patients to achieve hematologic response, and that following the JAK2V617F biomarker may be drug-dependent and may not always be a reliable measure of response. This warrants the importance of the randomized trial planned to compare peg-IFNá-2a to the current standard of treatment, hydroxyurea. Disclosures: No relevant conflicts of interest to declare.
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Granjard, Alexandre, Kevin M. Cloninger, Erik Lindskär, Christian Jacobsson, Sverker Sikström, Robert Cloninger, and Danilo Garcia. "PERSONALITY PROFILES IN A SWEDISH LONG-TERM UNEMPLOYED SAMPLE." International Journal of Person Centered Medicine 9, no. 4 (October 13, 2021): 17–39. http://dx.doi.org/10.5750/ijpcm.v9i4.1015.
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Background: Long-term unemployment is associated with psychiatric problems, higher risk of suicide, low levels of well-being, and high levels of burnout. In this context, among other factors such as sociodemographic status and IQ, specific personality traits are important for individuals’ chances to finding a job, getting hired, and retaining that job, as well as for coping with the mental health risks related to long-term unemployment. Thus, in order to use person-centered methods to promote public health and sustainable employment during the current and future challenges of the 21st century, an important research area is the mapping and understanding of personality profiles of individuals who are unemployed.
Objectives: We mapped the personality traits and profiles in a sample of Swedish long-term unemployed (i.e., ≥ 6 months without work) in relation to a control group from the Swedish general population.
Method: 245 long-term unemployed individuals (136 men and 157 women, range 18 to 60 years; M = 25.7; SD = 9.6) were recruited at the beginning of different well-being and employment projects in Blekinge, Sweden. The participants reported gender, age, and other basic demographics, as well as their personality using the Temperament and Character Inventory (TCI). We calculated the T-scores and percentiles for the personality traits using the Swedish normative data (N = 1,948) and clustered participants in different temperament (high/low novelty seeking: N/n, high/low harm avoidance: H/h, high/low reward dependence: R/r) and character profiles (high/low self-directedness: S/s, high/low cooperativeness: C/c, high/low self-transcendence: T/t).
Results: Compared to the general population, the long-term unemployed were extremely higher in harm avoidance (> 1.5 standard deviation), moderately lower in persistence (> 0.5 standard deviation), extremely lower in self-directedness (> 2 standard deviations), and moderately lower in novelty seeking (> 0.5 standard deviation). That is, consistent with past research, our study shows that the personality of long-term unemployed is denoted by being pessimistic, fearful, easily fatigable, underachieving, blaming, helpless, and unfulfilled (i.e., high harm avoidance, low persistence, and low self-directedness), but also by being reserved and rigid (i.e., low novelty seeking). Furthermore, within the unemployed population, as much as 71.60% reported a methodical (nHr) or cautious profile (nHR), and as much as 64.00% reported an apathetic (sct) or a disorganized profile (scT). Moreover, the profile analyses allowed us to show that, within this unemployed population and in relation to each individual’s own profile, about 91.70% were high in harm avoidance, 98.60% were low in self-directedness, 64.00% were low in cooperativeness, and 44.40% low in self-transcendence.
Conclusions: These results indicate a high predictive value by the TCI, especially regarding the specific basic health-related traits or abilities (i.e., self-directedness, cooperativeness, and self-transcendence) needed to cope with the risks related to unemployment. Specifically, long-term unemployed populations have temperament profiles that present difficulties for them to adapt to the circumstances of unemployment, but also finding, getting, and retaining a job and character profiles that diminish their possibilities to self-regulate the emotions derived from their temperament through self-directed choices that improve their health and all aspects of their lives. Hence, evidence-based interventions targeting stress reduction and the development of health-related traits or abilities (i.e., self-directedness, cooperativeness, and self-transcendence) are urgently needed.
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Patil, Varsha, and Tanuja Sarode. "Modified CSLBP." International Journal of Electrical and Computer Engineering (IJECE) 9, no. 4 (August 1, 2019): 2950. http://dx.doi.org/10.11591/ijece.v9i4.pp2950-2959.
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<p>Image hashing is an efficient way to handle digital data authentication problem. Image hashing represents quality summarization of image features in compact manner. In this paper, the modified center symmetric local binary pattern (CSLBP) image hashing algorithm is proposed. Unlike CSLBP 16 bin histogram, Modified CSLBP generates 8 bin histogram without compromise on quality to generate compact hash. It has been found that, uniform quantization on a histogram with more bin results in more precision loss. To overcome quantization loss, modified CSLBP generates the two histogram of a four bin. Uniform quantization on a 4 bin histogram results in less precision loss than a 16 bin histogram. The first generated histogram represents the nearest neighbours and second one is for the diagonal neighbours. To enhance quality in terms of discrimination power, different weight factor are used during histogram generation. For the nearest and the diagonal neighbours, two local weight factors are used. One is the Standard Deviation (SD) and other is the Laplacian of Gaussian (LoG). Standard deviation represents a spread of data which captures local variation from mean. LoG is a second order derivative edge detection operator which detects edges well in presence of noise. The proposed algorithm is resilient to the various kinds of attacks. The proposed method is tested on database having malicious and non-malicious images using benchmark like NHD and ROC which confirms theoretical analysis. The experimental results shows good performance of the proposed method for various attacks despite the short hash length.</p>
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Adkins, Daniel E., Shaunna L. Clark, William E. Copeland, Martin Kennedy, Kevin Conway, Adrian Angold, Hermine Maes, et al. "Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood." Twin Research and Human Genetics 18, no. 4 (June 17, 2015): 335–47. http://dx.doi.org/10.1017/thg.2015.36.
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The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples (N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR < 0.1) and six others met our ‘suggestive’ criterion (FDR <0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies.
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Acharya, Chetana, Alisha Dhungana, and Chiranjeebi Shah. "Nutritional Status and Associated Factors among the Elderly People in Mandavi Rural Municipality of Pyuthan District, Nepal." Journal of Health and Allied Sciences 11, no. 1 (August 18, 2021): 72–78. http://dx.doi.org/10.37107/jhas.236.
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Introduction: The geriatric population is increasing throughout the world. With the increase in age, people suffer from various chronic diseases and conditions. Nutrition-related problems are also common in elderly people. This study was conducted to assess the nutritional status and associated factors among elderly people.
Methods: A community-based cross-sectional descriptive and quantitative study was carried out among 124 elderly people of Mandavi Rural Municipality, Pyuthan, Nepal from September 2019 to November 2019. The study population was selected using a convenient method. Data collection was carried out through a structured questionnaire using the standard tool, mini nutritional assessment (MNA). Ethical approval was taken from Nepal Health Research Council (NHRC). Chi-square test was used to identify the association between independent variables and nutritional status.
Results: More than 1/4th of the total respondents had weight loss in the last three months. More than 1/4th of the participants had neuropsychological problem and psychological stress. Out of the studied population, 22.6 % had hypertension and 8.9% had diabetes. 18.5% were smokers while 40.3% were alcohol users. 40.3% were at risk of malnutrition and 4.0% were malnourished (MNA< 17.23). Sex (p = 0.04), smoking (p = 0.014), decline in food intake (p = 0.042), psychological stress (p = 0.03) and neuropsychological problem (p = 0.01) were found significantly associated with the nutritional status (p-value <0.05).
Conclusion: A significant proportion of participants were at the risk of malnourishment. Effective intervention should be designed to promote healthy aging among elders dwelling in rural areas.
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Rzepakowska, Anna, Ewa Osuch-Wójcikiewicz, Ewelina Sielska-Badurek, and Kazimierz Niemczyk. "Medialization thyroplasty in glottis insufficiency due to unilateral vocal fold paralysis and after laser cordectomies – preliminary report." Otolaryngologia Polska 71, no. 1 (February 28, 2017): 22–29. http://dx.doi.org/10.5604/01.3001.0009.5548.
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Medialization thyroplasty (type I) is surgical procedure performed on the thyroid cartilage. The major indication for this surgery is significant glottis insufficiency due to unilateral vocal fold paresis. However the proce¬dure is also performed after vocal fold resections during cordectomy. The aim: The evaluation of voice results in patients after medialisation throplasty. Material and methods: In Otolaryngology Department of Medical University of Warsaw there were performed so far 8 thyroplasty procedures under local anaesthesia with implantation of medical silicon protesis. 6 patients had unilat¬eral vocal fold paresis and the rest two underwent in the past laser cordectomy due to T1a vocal carcinoma. Results: There were no complications during and post the surgery. The follow up examination in 1st , 3rd, 6th i 12th months postoperatively revealed for all patients significant improvement of glottal closure in laryngeal videostrobos¬copy. The voice quality improved both in perceptual evaluation (GRBAS scale) and acoustic analysis (F0, jitter, shim¬mer, NHR) in both patients groups. However the rate of improvement was much more significant in group with uni¬lateral vocal fold paresis. In all patients the maximum phonation time (MPT) increased. The self-evaluation of voice quality with Voice Handicap Index questionnaire confirmed also individual improvement. Conclusions: The speech rehabilitations is not successful in each patient with glottis insufficiency. The medialisation thyroplasty remains the standard procedure for permanent improvement of voice quality in those cases.
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Huang, Huai-Hsuan, Chieh-Min Chen, Chen-Yu Wang, William Wei-Yuan Hsu, Ho-Min Chen, Bor-Sheng Ko, and Fei-Yuan Hsiao. "The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan." PLOS ONE 17, no. 1 (January 21, 2022): e0261871. http://dx.doi.org/10.1371/journal.pone.0261871.
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Backgrounds An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. Objectives The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. Methods We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. Results The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. Conclusions This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.
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Sah, Arun Kumar, Pradeep Belbase, Ashok Pandey, and Anjani Kumar Jha. "Are Health Agencies Designated as Research Centers in Nepal Conducting Adequate Researches ?" Journal of Nepal Health Research Council 17, no. 3 (November 13, 2019): 285–87. http://dx.doi.org/10.33314/jnhrc.v17i3.2054.
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Background: In Nepal, promoting quality research and enhancing research capacity is being accomplished through Nepal Health Research Council (NHRC). It also plays an authorized body to regulate, monitor and coordinate health research centers by maintaining the highest level of ethical standards. The aim of this study is to explore situation of health agencies designated as research center in Nepal.Methods: A cross sectional descriptive study design was used to carry out monitoring and follow up of activities of research centre of all seven provinces of Nepal that had title “Research” in their title name from January 2018 to July 2018.Results: There were only 81 research centers in Nepal and more than half (55 percent) of these have been found in Kathmandu valley, Province 3. Research found that 82.3% so called research centers were just health service provider and 10% of research institute were research based and just 5% have the core objectives of research. Likewise, 30% of research institute were actually involved in health related researches whereas large proportion (70%) of research institute were not involved in any kind of research work. Surprisingly, only 37.5% have taken ethical approval to conduct the designated research. Conclusions: Only one tenth of the research centers have mentioned research as their core business. However, less than one third of such centers were involved in heath research, and out of which, only 28 percent took ethical permission. Most of the research organizations want to conduct research but they do not have required research skills and competent manpower to carry out research.Keywords: Health research centers; monitoring; Nepal.
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Chen, Chien-Chih, Wei-Li Ho, Ching-Heng Lin, and Hsin-Hua Chen. "Stratified analysis of the association between periodontitis and female breast cancer based on age, comorbidities and level of urbanization: A population-based nested case-control study." PLOS ONE 17, no. 7 (July 26, 2022): e0271948. http://dx.doi.org/10.1371/journal.pone.0271948.
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Purpose To conduct stratified analysis of the association between periodontitis exposure and the risk of female breast cancer based on age, comorbidities and level of urbanization. Methods Using claims data taken from the 1997–2013 Taiwanese National Health Insurance Research Database (NHIRD), we identified 60,756 newly-diagnosed female breast cancer patients during the period 2003–2013 from all beneficiaries. We then randomly selected 243,024 women without breast cancer matching (1:4) for age and the year of the index date during 1997–2013 from a one million representative population acting as the control group. A conditional logistic regression analysis was used to examine the association between periodontitis (ICD-9-CM codes 523.3–4) and the risk of breast cancer, shown as an odds ratio (OR) with a 95% confidence interval (CI) after adjustments for the Charlson Comorbidity Index (CCI) and level of urbanization. Subgroup analyses were conducted based on age, CCI and level of urbanization. Results The mean ± standard deviation age was 53 ± 14 years. After adjusting for potential confounders, the risk of female breast cancer was found to be associated with a history of periodontitis (OR, 1.12; 95% CI, 1.10–1.14). Such an association was significantly different between patients aged < 65 years (OR, 1.09; 95% CI, 1.06–1.11) and patients aged ≥ 65 years (OR, 1.23; 95% CI, 1.18–1.28; p for interaction <0.001), as well as between patients where the CCI = 0 (OR, 1.17; 95% CI, 1.15–1.20) and patients with CCI > 0 (OR, 0.99; 95% CI, 0.96–1.03; p for interaction <0.001). The highest level of urbanization was also associated with the risk of breast cancer. Conclusions This population-based nested case-control study demonstrated that periodontitis was significantly associated with the risk of female breast cancer and such an association was modified by both age and comorbidities.
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Merriam, Eric R., Michael P. Strager, and J. Todd Petty. "Source water vulnerability to elevated total dissolved solids within a mixed-use Appalachian River basin." PLOS Water 1, no. 8 (August 24, 2022): e0000035. http://dx.doi.org/10.1371/journal.pwat.0000035.
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The upper Monongahela River basin in West Virginia represents a watershed wherein historic land use activities, including coal mining, conventional oil and gas development, and residential and urban development have contributed to elevated total dissolved solids (TDS) concentrations within surface and source waters with widespread exceedance of the 500 mg/L secondary drinking water standard for TDS. Our research was designed to characterize spatial variability in and sources of elevated and assess vulnerability of surface and source waters to additional TDS sources and loading. We compiled 3439 unique water quality sampling records throughout the study area over a ten-year period and applied boosted regression tree (BRT) analysis to model log[x]-transformed TDS as a function of landscape attributes across the 885 sampled NHD catchments. We predicted (i.e., elevated TDS and reduced dilution capacity) and observed (i.e., increased variability in TDS and temporary exceedances of 500 mg/L) elevated vulnerability of source waters, with vulnerability being largely driven by a few dominant contributors of TDS throughout the stream network. Notably, seven 12-digit hydrologic unit code (HUC) inflows to the Monongahela River and its vulnerable tributaries were predicted to require a combined 6,664,879 m3 of water (i.e., chemical footprint) to dilute TDS concentrations below 500 mg/L from July through September. Our results provide insights into how the mixed land uses containing extractive industries can impact water quality and demonstrates the importance of both spatial and temporal processes in controlling vulnerability of source waters to water pollution.
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Martinez, Michael A. Q., Brian A. Kinney, Taylor N. Medwig-Kinney, Guinevere Ashley, James M. Ragle, Londen Johnson, Joseph Aguilera, Christopher M. Hammell, Jordan D. Ward, and David Q. Matus. "Rapid Degradation of Caenorhabditis elegans Proteins at Single-Cell Resolution with a Synthetic Auxin." G3: Genes|Genomes|Genetics 10, no. 1 (November 14, 2019): 267–80. http://dx.doi.org/10.1534/g3.119.400781.
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As developmental biologists in the age of genome editing, we now have access to an ever-increasing array of tools to manipulate endogenous gene expression. The auxin-inducible degradation system allows for spatial and temporal control of protein degradation via a hormone-inducible Arabidopsis F-box protein, transport inhibitor response 1 (TIR1). In the presence of auxin, TIR1 serves as a substrate-recognition component of the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF), ubiquitinating auxin-inducible degron (AID)-tagged proteins for proteasomal degradation. Here, we optimize the Caenorhabditis elegans AID system by utilizing 1-naphthaleneacetic acid (NAA), an indole-free synthetic analog of the natural auxin indole-3-acetic acid (IAA). We take advantage of the photostability of NAA to demonstrate via quantitative high-resolution microscopy that rapid degradation of target proteins can be detected in single cells within 30 min of exposure. Additionally, we show that NAA works robustly in both standard growth media and physiological buffer. We also demonstrate that K-NAA, the water-soluble, potassium salt of NAA, can be combined with microfluidics for targeted protein degradation in C. elegans larvae. We provide insight into how the AID system functions in C. elegans by determining that TIR1 depends on C. elegansSKR-1/2, CUL-1, and RBX-1 to degrade target proteins. Finally, we present highly penetrant defects from NAA-mediated degradation of the FTZ-F1 nuclear hormone receptor, NHR-25, during C. elegans uterine-vulval development. Together, this work improves our use and understanding of the AID system for dissecting gene function at the single-cell level during C. elegans development.
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Noor Zahra, Syeda Mah-e., Saadia Shahzad Alam, Maryam Nadeem, Huma Zia Arain, Neelofer Warraich, and Maryam Piracha. "Comparative Evaluation of Prophylactic and THP of CO (Hawthorn) Fruit with Atorvastatin in Murine Model of Dyslipidemia." Pakistan Journal of Medical and Health Sciences 15, no. 11 (November 30, 2021): 2913–16. http://dx.doi.org/10.53350/pjmhs2115112913.
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Background: Dyslipidemia or hyperlipidemia is a consequential condition resulting from derangement in lipid profile. Standard treatment such as Atorvastatin though beneficial, causes many serious adverse effects thus an alternative like Crataegus oxyacantha (Hawthorn) with hypolipidemic potential was investigated. Aims: To evaluate prophylactic and therapeutic hypolipidemic potential of crataegus oxyacantha (hawthorn) fruit in comparison with atorvastatin in murine model of dyslipidemia through assessing physiological parameter i.e., weight and serum biochemical parameters i.e., lipid profile: TC, TGs, VLDL, LDL and HDL. Study design: This experimental study was carried out in research laboratory of Akhtar Saeed Medical and Dental College and National Health Research Centre (NHRC), Lahore Methods: A murine study of 60 days was conducted on 64 male albino Wistar rats (Age 6 weeks) divided into 8 groups with 8 rats each weighing 180-200 grams. Group 1 (healthy control) received normal diet and 2 ml of normal saline for 60 days. Group 2 (disease control) received HFD and 2 ml of normal saline for 30 days while 3-5 (prophylactic groups) were given HFD along with ethanolic extract of Crataegus oxyacantha fruit, atorvastatin and their combination in doses of 40 mg/kg OD, 80 mg/kg OD and 20+40 mg/kg OD orally respectively for the same period. 6-8 (therapeutic groups) received ethanolic extract of Crataegus oxyacantha fruit, atorvastatin and their combination respectively after induction of dyslipidemia from 30th till 60th day in the same doses as mentioned above. Each rat was weighed and fasting samples for biochemical parameters were drawn by cardiac puncture in all groups at baseline and repeated at 30th day in all groups while also at 60th day in therapeutic groups as well as healthy control group. The results were analyzed using one way ANOVA for Mean±SD, post hoc Tukey’s test for group comparison in the Graph-Pad Prism (V.5) software. A p-value ≤ 0.05 was considered as statistically significant. Study period: This study was conducted from September, 2020-November, 2020. Results: Our murine study concludes that Crataegus oxyacantha (40 mg/kg OD orally) when administered prophylactically and therapeutically shows a noteworthy hypolipidemic potential when compared with Atorvastatin (80mg/kg OD orally). Better results were obtained in prophylactic doses as well as in low dose combination with Atorvastatin (20 mg/kg + 40 mg/kg respectively). Conclusion: Results suggest that Crataegus oxyacantha can be used as alternative in treating hyperlipidemias. Keywords: Crataegus oxyacantha, Atorvastatin, Hyperlipidemia.
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Zahra, Syeda Mah-E.-Noor, Saadia Shahzad Alam, Maryam Nadeem, Huma Zia Arain, Neelofer Warraich, and Maryam Piracha. "Comparative Evaluation of Prophylactic and Therapeutic Hypolipidemic Potential of Crataegus Oxyacantha Fruit with Atorvastatin in Murine Model of Dyslipidemia." Pakistan Journal of Medical and Health Sciences 16, no. 1 (January 16, 2022): 25–28. http://dx.doi.org/10.53350/pjmhs2216125.
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Background: Dyslipidemia or hyperlipidemia is a consequential condition resulting from derangement in lipid profile. Standard treatment such as Atorvastatin though beneficial, causes many serious adverse effects thus an alternative like Crataegus oxyacantha (Hawthorn) with hypolipidemic potential was investigated. Aims: To evaluate prophylactic and therapeutic hypolipidemic potential of crataegus oxyacantha (hawthorn) fruit in comparison with atorvastatin in murine model of dyslipidemia through assessing physiological parameter i.e., weight and serum biochemical parameters i.e., lipid profile: TC, TGs, VLDL, LDL and HDL. Study design: This experimental study was carried out in research laboratory of Akhtar Saeed Medical and Dental College and National Health Research Centre (NHRC), Lahore Methods: A murine study of 60 days was conducted on 64 male albino Wistar rats (Age 6 weeks) divided into 8 groups with 8 rats each weighing 180-200 grams. Group 1 (healthy control) received normal diet and 2 ml of normal saline for 60 days. Group 2 (disease control) received HFD and 2 ml of normal saline for 30 days while 3-5 (prophylactic groups) were given HFD along with ethanolic extract of Crataegus oxyacantha fruit, atorvastatin and their combination in doses of 40 mg/kg OD, 80 mg/kg OD and 20+40 mg/kg OD orally respectively for the same period. 6-8 (therapeutic groups) received ethanolic extract of Crataegus oxyacantha fruit, atorvastatin and their combination respectively after induction of dyslipidemia from 30th till 60th day in the same doses as mentioned above. Each rat was weighed and fasting samples for biochemical parameters were drawn by cardiac puncture in all groups at baseline and repeated at 30th day in all groups while also at 60th day in therapeutic groups as well as healthy control group. The results were analyzed using one way ANOVA for Mean±SD, post hoc Tukey’s test for group comparison in the Graph-Pad Prism (V.5) software. A p-value ≤ 0.05 was considered as statistically significant. Study period: This study was conducted from September, 2020-November, 2020. Results: Our murine study concludes that Crataegus oxyacantha (40 mg/kg OD orally) when administered prophylactically and therapeutically shows a noteworthy hypolipidemic potential when compared with Atorvastatin (80mg/kg OD orally). Better results were obtained in prophylactic doses as well as in low dose combination with Atorvastatin (20 mg/kg + 40 mg/kg respectively). Conclusion: Results suggest that Crataegus oxyacantha can be used as alternative in treating hyperlipidemias. Keywords: Crataegus oxyacantha, Atorvastatin, Hyperlipidemia.
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Liang, Der-Cherng, Lee-Yung Shih, Ming-Chung Kuo, Chao-Ping Yang, Hsi-Che Liu, Tang-Her Jaing, Jen-Fen Fu, Yu-Shu Shih, and Tung-Huei Lin. "Co-Existing Gene Mutations at Diagnosis and at Relapse in De Novo Acute Myeloid Leukemia with MLL Translocations." Blood 124, no. 21 (December 6, 2014): 1008. http://dx.doi.org/10.1182/blood.v124.21.1008.1008.
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Abstract Background and purpose: The Mixed-lineage leukemia (MLL) gene located at 11q23 can be fused to a variety of partner genes through chromosomal translocations (MLL-T) in acute leukemia. The co-existence of commonly known mutated genes has not been comprehensively studied in MLL-T AML. We aimed to determine (1) the prevalence and clinical relevance of gene mutations at diagnosis, and (2) the genetic evolution profile at relapse in de novo AML with MLL-T. Materials and methods: Bone marrow samples from 80 de novo AML with MLL-T patients were analyzed on 20 gene mutations involving activating signaling pathway (class I), transcription pathway (class II), epigenetic regulators (class III), and tumor suppressors, TP53 and WT1 (class IV). MLL-T was all confirmed by FISH analysis. The common MLL fusion transcripts were detected by RT-PCR, including 26 MLLT3, 13 MLLT10, 12 MLLT4, 11 ELL, 3 MLLT1, 3 AFF1, and 2 EPS1. Another 6 infrequent or rare partner genes (one each of MLLT6,CBL, ARHGEF12, TET1, SEPT6, and SEPT9) were identified by cDNA panhandle PCR. In the remaining 4 cases, the partner genes were not identified. Mutational analyses were performed with PCR-based assays followed by direct sequencing. Twenty-two of 26 patients who relapsed had relapse samples for comparative analysis. Results: The frequencies of gene mutations of class I, II, III, and IV, in 80 de novo MLL-T AML patients were 49.4%, 3.8%, 10.3% and 1.3%, respectively. Together, 53.8% of patients with MLL-T had at least one mutated gene. KRAS (17.7%), FLT3-TKD (11.5%), and NRAS (11.4%) mutations occurred most frequently. Among the epigenetic regulators, 7.9% of patients had DNMT3A, 2.7% TET2, 1.4% ASXL1, and none had IDH1/2 or EZH2 mutations. Three patients had 3 co-existing mutations and 9 patients had two mutations, with 6 of the 12 carrying FLT3-TKD mutations. Gene mutations of transcription pathway and tumor suppressors rarely occurred, only involving NPM1 in two cases and one each for RUNX1 and WT1 mutation. The patients with DNMT3A mutations were significantly associated with older age (P=0.005), FAB AML-M4 (P<0.0001), and higher circulating monocytes (P=0.022). Patients with NRAS mutations had lower circulating monocytes (P<0.0001). KRAS-mutated patients had a higher percentage of marrow leukemic cells (P=0.002). No differences were observed between clinico-hematological features and mutation status of other genetic subtypes. Of the 65 MLL-T AML patients who received standard chemotherapy, 53 achieved complete remission. There were no differences in the outcomes between AML patients with MLLT3-MLL and MLL-MLLT10; patients with both subtypes had a superior event-free survival compared to those with other MLL-fusion transcripts (P=0.036) and a trend towards favorable overall survival (P=0.066). We failed to find significant differences between outcomes and the mutation status of each functional class. All the 3 patients carrying FLT3-ITD had an overall survival less than 6 months. Of the 22 paired diagnosis and relapse samples, 3 patients retained the same NRAS mutations at relapse whereas another one changed from G12D to G12C at relapse. Another 3 relapsed with identical KRAS mutations; while one acquired KRAS mutation at relapse. Two patients had stable DNMT3A mutations at both phases. All the 4 patients who harbored FLT3-TKD mutations at diagnosis lost the mutations at relapse. PTPN11 mutation was found in only one case at diagnosis, while none at relapse. One each had identical mutated gene of CBL and WT1 at both diagnosis and relapse. One each acquired TP53 and WT1 at relapse. Conclusions: Our results showed that co-existing mutations of RAS and FLT3-TKD were most frequently detected at diagnosis in de novo MLL-T AML. Gene mutations, except FLT3-ITD, had no impact on outcomes in MLL-T AML. FLT3-TKD mutations were absent in all relapse samples while clonal evolution of WT1, TP53 or KRAS mutations might contribute to the relapse of leukemia in a subset of MLL-T AML patients. Grant support: NHRI-EX93-9011SL, NHRI-EX96-9434SI, NSC95-2314-B-195-001, NSC96-2314-B-195-006-MY3, NSC97-2314-B-182-011-MY3, MMH-E-101-09 and OMRPG3C0021. Disclosures No relevant conflicts of interest to declare.
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Merzah, Mohammed, Zsigmond Kósa, János Sándor, Shewaye Natae, Péter Pikó, Róza Ádány, and Szilvia Fiatal. "Roma Socioeconomic Status Has a Higher Impact on Smoking Behaviour than Genetic Susceptibility." International Journal of Environmental Research and Public Health 18, no. 6 (March 19, 2021): 3206. http://dx.doi.org/10.3390/ijerph18063206.
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It is a matter of speculation whether the high prevalence of smoking among Hungarian Roma (HR) is related to genetic, gene-environmental interactions or cultural factors. Our aim is to compare the genetic susceptibility and possible effects of determinants associated with smoking behaviours in the Hungarian general (HG) and Roma populations. A complex health survey including three pillars (questionnaire, physical and laboratory examinations) was carried out (NHG = 412 and NHR = 402). Risk allele frequencies of ten single-nucleotide polymorphisms (SNPs) were compared, and their combined effect was estimated by computing unweighted and weighted genetic risk scores (GRS, wGRS). The effects of genetic and environmental factors were investigated in regression analyses after confounders were introduced. Socio-economic status (SES) was calculated based on the Kuppuswamy scale 2019. Risk allele frequencies of only four SNPs were found to be different between populations (p < 0.01). Median values of GRS did not differ, while the wGRS median was slightly higher among Roma individuals (5.2 vs. 4.9; p = 0.02). Roma individuals were more likely to be heavy smokers (ORmales = 2.05, 95% CI [1.47–2.86]; ORfemales = 1.89, 95% CI [1.58–2.25]. Smokers have lower SES compared to never smokers (SES βHR = −0.039, p = 0.023; βHG = −0.010, p = 0.049). An inverse relationship was found between SES and smoking behaviours (p < 0.0001) and was found to be a better predictor of smoking behaviours than genetic susceptibility. Our study findings suggest that the high prevalence of smoking behaviours and nicotine-dependence were not revealed to have a genetic susceptibility among HR individuals; therefore, the highest efforts should be focused on targeting SES-related factors in the Roma population. Strengths of the study: This is the first study carried out to investigate and detect the most relevant factors and the possible genetic background of the extremely high prevalence of smoking based in the Roma population. Limitations of the study: No standard instrument has been used to assess the intensity of addiction to nicotine. Because of some participants’ unwillingness to define themselves as Roma, the overall HR population was not represented by the sample of this study.
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Tang, Chao-Hsiun, Wesley Furnback, Bruce C. M. Wang, Jackson Tang, Vicky Wei-Hsuen Huang, Derek Tang, Meng-Yao Lu, and Khaled M. Musallam. "Greater Red Blood Cell Transfusion Burden Is Associated with More Healthcare Resource Utilization in Patients with Beta-Thalassemia." Blood 134, Supplement_1 (November 13, 2019): 5790. http://dx.doi.org/10.1182/blood-2019-122747.
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Introduction: Previous studies have examined the total healthcare resource utilization (HCRU) of patients with beta-thalassemia in relation to the general population. However, limited studies have examined the impact of red blood cell transfusion (RBCT) burden on broad aspects of HCRU beyond transfusion costs among patients with beta-thalassemia. Methods: Patients with beta-thalassemia in Taiwan's National Health Insurance Research Database (NHIRD) in 2016 were identified (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] of D56.1). The index date was the first medical claim in the database after 2001. Identified patients were followed from the index date until the end of the study period (December 31, 2016). During the follow-up period, RBCT units and HCRU (all-cause and thalassemia-related) were measured. Thalassemia-related HCRU was defined as any HCRU claim accompanied by a thalassemia or beta-thalassemia diagnosis code. To control for the different lengths of follow-up between patients, both RBCT units and HCRU were reported as the average per 12 weeks over the entire follow-up period. Patients were categorized into 4 cohorts based on the average number of RBCT units received per 12 weeks during follow-up: 0 RBCT units; > 0 to < 6 RBCT units; ≥ 6 to < 12 RBCT units; or ≥ 12 RBCT units. HCRU outcomes of interest were hospital admissions, hospitalized days, outpatient visits, and emergency room (ER) visits. Descriptive statistics were computed to describe HCRU observed in each cohort. Results: A total of 2,984 patients with beta-thalassemia were included in the analysis, with a mean follow-up of 6.87 years. Mean age at index was 37.8 (standard deviation 23.7) years, and 1,903 (63.8%) patients were female. A total of 1,616 (54.2%) patients did not receive RBCT units during the follow-up period. Of the remaining 1,368 patients, 1,112 (81.3%) received > 0 to < 6 RBCT units, 112 (8.2%) received ≥ 6 to < 12 RBCT units, and 144 (10.5%) received ≥ 12 RBCT units per 12 weeks during follow-up. Mean all-cause and thalassemia-related HCRU was higher for transfused patients than for non-transfused patients across all HCRU categories. Thalassemia-related hospital admissions, hospitalized days, and outpatient days all increased as the transfusion burden increased. Patients in the cohort with the highest average transfusion burden (≥ 12 RBCT units per 12 weeks) had numerically greater mean thalassemia-related hospital admissions (0.5; standard error [SE] = 0.04), hospitalized days (2.5; SE = 0.21), and outpatient visits (4.9; SE = 0.41) than the other cohorts (Figure). Conclusions: Patients with beta-thalassemia and higher average transfusion burden during the follow-up period had additional HCRU compared with patients who required fewer RBCT units. These data may support physician and payer understanding of the downstream economic impact of RBCT burden in beta-thalassemia. Disclosures Tang: GSK: Consultancy; Roche: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Amgen: Research Funding. Furnback:Sanofi: Consultancy; Regeneron: Consultancy; Celgene Corporation: Consultancy; Abbott: Consultancy; Astellas: Consultancy; Pfizer: Consultancy; Eli Lilly: Consultancy; Janssen: Consultancy; Johnson & Johnson: Consultancy; Gilead: Consultancy; Novocure: Consultancy; Progentec Diagnostics: Consultancy; Becton Dickinson: Consultancy; AstraZeneca: Consultancy; Bristol-Myers Squibb: Consultancy. Wang:Gilead Sciences: Consultancy, Equity Ownership; Celgene Corporation: Consultancy, Equity Ownership; Regeneron Pharmaceuticals: Consultancy, Equity Ownership; Novocure: Consultancy; Pfizer: Consultancy; Eli Lilly: Consultancy; Johnson & Johnson: Consultancy; Astellas: Consultancy; Amgen, Vertex Pharma, Illumina, Biogen, Alexion Pharma, Incyte, Biomarin Pharma, Seattle Genetics, Sarepta Therapeutics, Array Biopharma, Ionis Pharma, Sage Therapeutics, Mylan NV, Neurocrine Biosciences, Bio Techne Corp, Jazz Pharma, Alnylam Pharma, Blue: Equity Ownership. Tang:Asclepius Analytics: Employment. Huang:Celgene Corporation: Employment. Tang:Celgene Corporation: Employment, Equity Ownership. Musallam:Celgene Corporation: Consultancy.
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Foran, James M., Zhuoxin Sun, David F. Claxton, Hillard M. Lazarus, Mary L. Thomas, Ari Melnick, Ross L. Levine, et al. "North American Leukemia, Intergroup Phase III Randomized Trial of Single Agent Clofarabine As Induction and Post-Remission Therapy, and Decitabine As Maintenance Therapy in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age ≥60 Years): A Trial of the ECOG-ACRIN Cancer Research Group (E2906)." Blood 126, no. 23 (December 3, 2015): 217. http://dx.doi.org/10.1182/blood.v126.23.217.217.
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Abstract Background: Induction therapy with daunorubicin (Dauno) & cytarabine (Ara-C) [DA] has been the standard of care for eligible older adults (age ≥ 60 years) with newly diagnosed acute myeloid leukemia (AML) for over 2 decades. Single agent Clofarabine (CLO) induction & consolidation (Consol.) therapy has demonstrated important clinical activity in this age group in large phase II studies. Lower induction mortality (IM) & similar reported complete remission rate (CR) & overall survival (OS), as well as notable activity in those with higher risk disease features [including unfavorable cytogenetics, therapy-related AML (t-AML) & prior antecedent hematologic disorder (AHD)] raises the possibility that a non-Ara-C-based regimen could achieve similar or superior OS with lower toxicity. Methods: We performed a randomized United States Intergroup Phase III trial of single agent CLO [30mg/m2 x 5 days induction; 20 mg/m2 re-induction (if indicated) & 2 cycles Consol.] vs. standard DA therapy [Dauno 60mg/m2 D1-3 & Ara-C 100mg/m2 D1-7 induction x 1-2 cycles; 2 cycles Consol. with Ara-C (1.5g/m2 Q12hrs D1-6 age 60-69; once daily if age 70+)] in patients (pts) age ≥ 60 yrs with newly diagnosed AML. Patients with serum creatinine >1.0 (or GFR <60 mL/min) and those with AML-M3 and ECOG performance status >3 (PS>2 if age 70+ yrs) were excluded. Randomization was stratified by age (60-69 vs. 70+), t-AML, & AHD. Pts with HLA-matched donor were eligible for allogeneic transplantation (AlloHCT) after induction, and those completing Consol. were eligible for randomization #2 (R#2) to maintenance decitabine [20mg/m2 x 3D, monthly x 1 year] versus observation. With a target accrual of 747, E2906 was powered to determine non-inferiority [and possible superiority] of CLO vs. standard DA, and primary endpoint was OS. A weighted statistical analysis was performed to account for confounding impact of R#2. AlloHCT patients were censored at transplant in this analysis. Responses & cytogenetics were confirmed centrally and OS & CR rates were monitored by an independent Data Safety Monitoring Committee (DSMC) at pre-specified time points. Results: As of Feb 23, 2015, 727 pts were randomized. Median age was 68 years (range 60-86); 57% were male, and 38% were age ≥70 yrs. Treatment arms are well balanced for all baselineclinical & AML characteristics, & 30% had unfavorable cytogenetics. Of 659 with complete treatment information reported, 30.4% on DA vs. 40.1% on CLO received 2 cycles of induction (p=0.006). Median follow-up of surviving patients is 7.6 months. Table 1. shows early treatment results (CR, toxicity) for the 686 pts randomized as of Dec 23, 2014 (2 months prior to study end, & excluding 90 with ongoing response evaluation). DA CLO p-value CR/CRi 43.8% 42.8% p=0.87 30-day mortality 8.5% 7.9% p=0.89 60-day mortality 14.9% 13.1% p=0.58 Gr 4-5 Non-Heme Tox.Induction 27% 19% p=0.02 Gr 4-5 Non-Heme Tox.Consol. 20% 7% p=0.001 374 pts have died (174, DA; 200, CLO) & significantly inferior OS was observed for CLO vs. DA [Hazard Ratio (HR) 1.41 (95% CI 1.12-1.78)] (Fig. 1). Planned subgroup analyses were performed (Table 2) demonstrating significant differences in OS after CLO for patients age 60-69 yrs, without AHD, & with intermediate risk cytogenetics; but not for those with Unfav. Cytogen. (Fig. 2) or t-AML. Based on the primary weighted analysis, DSMC recommended suspension of new accrual to E2906 on Feb 23, 2015 & all active patients on CLO were transitioned to DA Arm. Table 2.NHR CLO/Standard (95% CI)*Weighted OS7271.41 (1.12-1.78)Unweighted OS7271.23 (1.00-1.50)Age 60-694491.48 (1.10-1.99)Age 70+2781.34 (0.93-1.93)Intermed. Risk Cytogen.3781.77 (1.27-2.47)Unfav. Risk Cytogen.2160.96 (0.65-1.43)No AHD6041.46 (1.13-1.89)AHD1231.22 (0.74-2.00)De novo AML6271.52 (1.18-1.96)Therapy-related AML1000.94 (0.54-1.61) Conclusions: Despite similar CR & IM, OS after single agent CLO is inferior to standard DA therapy for pts age ≥60 years with newly diagnosed AML who are fit for intensive therapy, and DA remains the standard of care. However no difference in OS was observed after CLO in some pre-specified high risk AML subgroups. R#2 & AlloHCT arms continue in E2906 for pts already enrolled. Embedded prospective minimal residual disease study at CR is being performed to identify pts at higher risk after CLO & DA. Figure 1. Weighted Kaplan-Meier Curves for OS Figure 1. Weighted Kaplan-Meier Curves for OS Figure 2. Unfavorable Cytogenetics OS by Therapy Figure 2. Unfavorable Cytogenetics OS by Therapy Disclosures Off Label Use: Use of clofarabine in AML, and maintenance therapy with decitabine in AML. Claxton:Medimmune: Research Funding; BMS: Consultancy; Astellas: Research Funding; Cyclacel: Research Funding; Merck: Research Funding; Ambit: Research Funding. Levine:Loxo Oncology: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Foundation Medicine: Consultancy. Altman:Seattle Genetics: Consultancy; BMS: Consultancy; Spectrum: Consultancy; Astellas: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Al-Kali:Novartis: Research Funding.
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Van den Heuvel-Eibrink, Marry M., Inge M. Van der Sluis, Bert A. Leeuw, Gaby Kardos, Lizet M. te Winkel, Tom Revesz, Elisabeth T. Korthof, Jos Bokkerink, and Anjo J. P. Veerman. "Bone Mineral Density, Fracture Risk and Avascular Bone Necrosis in Childhood Acute Lymphoblastic Leukemia; an Up-Date of the Prospective DUTCH ALL9 Study." Blood 104, no. 11 (November 16, 2004): 1962. http://dx.doi.org/10.1182/blood.v104.11.1962.1962.
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Abstract The high cumulative dose of dexamethasone, applied in the DCOG ALL9 protocol, prompted us to investigate the risk of osteoporosis, fractures and avascular necroses of bone (AVN) in children treated with acute lymphoblastic leukemia (ALL). Fracture risk and incidence of symptomatic AVN was assessed in 778 patients(482 boys, 297 girls), included in the ALL9 protocol since 1997. Total cumulative doses (TCD) of dexamethasone were 1370 mg/m2 and 1244 mg/m2 and of MTX 8.1g/m2 13.6g/m2 for NHR and HR patients respectively. No CNS-irradiation was applied. In children aged >3 years, lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXAscan), at diagnosis(T0), after 32 weeks(T1), at discontinuation of treatment at 109 weeks(T2), and one year after discontinuation of treatment(T3). Results were expressed as standard deviation scores (SDS). Symptomatic AVN was defined as on MRI confirmed AVN lesions in combination with non-vincristine related persistent pain in arms or legs. Fractures were reported in 82/778 (10.5%) patients. Most occurred after mild trauma. No difference was found in fracture incidence between boys and girls. BMD was measured in 387/427 (90.6%) eligible patients. Median BMD-SDS was significantly lower than zero at all times of evaluation, the lowest BMD values were found at T2 (−1.47 SDS). Fracture risk was 3.9 times higher as compared to healthy school children. Fracture incidence was correlated with BMD at T2 and T3(p=0.04 and p=0,04 respectively), but not at T0 and T1. A significant more rapid decline in BMD from T0 to T2 and to T3 was seen in patients with fractures as compared to patients without fractures. After discontinuation of therapy, BMD recovered faster in cases without fractures. Symptomatic AVN occurred in 33/778 (4.2%) of our patients (med age 14, range 6,5–18 years) showing irreversibility in 22 % of the cases. Differences found in the incidence between the centers may suggest underestimation of the risk of fractures and AVN in this prospective study. Children with ALL show a significantly increased fracture risk. Patients with a more severe reduction in BMD during treatment are more susceptible to fractures. The AVN incidence in this protocol did not exceed previous reports of prednisolone-based protocols.
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Kao, Hsiao-Wen, Lee-Yung Shih, Ming-Chung Kuo, Tung-Liang Lin, Sung-Tzu Liang, Chao-Ping Yang, Yu-Shu Shih, Yu-Hui Huang, Tung-Huei Lin, and Der-Cherng Liang. "Mutations Of Genes Regulating DNA Methylation Are Common In MLL Partial Tandem Duplication AML and DNMT3A Mutations Are Associated With Adverse Outcome." Blood 122, no. 21 (November 15, 2013): 1407. http://dx.doi.org/10.1182/blood.v122.21.1407.1407.
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Abstract Background and purpose Abnormalities of genes regulating DNA methylation have been described in acute myeloid leukemia (AML). MLL protein is a transcriptional regulator and governs proper hematopoiesis through its histone methyltransferase activity. AML with partial tandem duplication of MLL (MLL-PTD) was associated with an unfavorable prognosis. The cooperating roles of MLL-PTD with other mutated genes regulating DNA methylation have not been comprehensively studied in AML. We aimed to determine the prevalence and clinical impact of mutations of DNA methylation regulators in AML with MLL-PTD. Materials and methods Bone marrow samples from 98 AML patients with MLL-PTD were analyzed for gene mutations of TET2, DNMT3A, IDH1 and IDH2. MLL-PTD was screened by RT-PCR and confirmed by real-time quantitative PCR assays. The mutational analysis was performed with PCR assays followed by direct sequencing for TET2 (whole coding exons 3–11) and IDH1/2 (hotspots exon 4). For the detection of DNMT3A mutations, the PCR products amplified for entire coding exons 2 to 23 were first screened with denaturing high-performance liquid chromatography followed by direct sequencing for the abnormal profiles. Results The frequency of TET2, IDH1, IDH2 and DNMT3A mutations in AML patients with MLL-PTD was 17.0% (16/94), 10.2% (10/98), 18.4% (18/98), and 31.6% (31/98), respectively. Taken together, 61.1% of patients with MLL-PTD had at least one mutated gene of DNA methylation regulators. TET2, IDH1 and IDH2 mutations were mutually exclusive with each other whereas DNMT3A mutations frequently co-existed with other DNA methylation modifiers:TET2 (n=8), IDH1 (n=5) and IDH2 (n=4). No differences were observed between the mutation status of the DNA methylation modifiers and clinico-hematologic features of patients with MLL-PTD except that TET2 (P=0.012) and DNMT3A (P=0.024) mutations were associated with older age. Of the 55 MLL-PTD patients who received standard chemotherapy, IDH2 mutation was associated with a lower complete remission rate (25.0% vs 67.8%, P=0.018), while DNMT3A mutations conferred an inferior event-free survival (0.0 vs 6.8 months, P=0.027) and overall survival (6.0 vs 11.5 months, P=0.032). In multivariate analysis, older age (P=0.008) and DNMT3A mutations (P=0.049) were independent adverse factors for overall survival. The crosstalk between MLL-PTD and genes involving DNA methylation in the leukemogenesis of AML warrants further investigation. Conclusions Gene mutations involving DNA methylation frequently co-existed in AML patients with MLL-PTD, especially DNMT3A mutations which conferred a poor outcome. Our study demonstrated the importance of genetic alterations involving DNA methylation in the pathogenesis of MLL-PTD AML and provided potential epigenetic-targeted therapy. Grant support The work was supported by NHRI-EX93-9011SL, NSC95-2314-B-195-001, NSC96-2314-B-195-006-MY3, NSC97-2314-B-182-011-MY3 and MMH-E-101-09. Disclosures: No relevant conflicts of interest to declare.
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Lombardo, Nicola, Giovanna Piazzetta, Nadia Lobello, Corrado Pelaia, Francesco Longo, Domenico Testa, Franco Ionna, Girolamo Pelaia, Desiderio Passali, and Gaetano Motta. "Speech outcome in tongue cancer surgery: objective evaluation by acoustic analysis software." Romanian Journal of Rhinology 11, no. 44 (November 3, 2021): 143–52. http://dx.doi.org/10.2478/rjr-2021-0025.
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Abstract BACKGROUND. Cancer of the oral cavity is one of the most common malignancies of which 60% affect the tongue. Carcinoma of the tongue causes significant alterations of the articulatory and swallowing functions. The gold standard of care remains primary surgical resection with or without postoperative adjuvant therapy. Whereas T1 and T2 tongue tumors can be treated with more conservative surgeries, as partial glossectomies, the larger tumors require total and aggressive glossectomies which increase survival, but, on the other hand, they might often make speech, chewing and swallowing impossible. MATERIAL AND METHODS. Our study was performed on a total of 21 patients with Squamous Cell Carcinoma of the tongue who underwent either partial resection or hemiglossectomy. Each subject (either surgical patients or controls) was asked to pronounce the vowels /a/, /e/, /i/, /u/, and all signals were evaluated separately by two operators. Acoustic (F0, jitter, shimmer, NHR) and vowel metric (the ratio F2i/F2u, tVSA, qVSA, FCR) features have been extracted. In order to define the speech intelligibility, all patients were evaluated by two doctors and one speech therapist and all patients received the Speech Handicap Index (SHI) translated into Italian language before recording. RESULTS. No statistically significant variations were observed, regardless of the gender, between controls and surgically resected patients when tumor staging was T1-T2. On the contrary, when patients had to undergo more extensive surgical resection due to the presence of a T3-T4 tumor, a dramatic increase of F2u could be observed. This change, together with a decrease of F2i, led to a highly significant reduction in the F2i/F2u parameter in surgically resected patients as compared to controls. The other parameters which were reduced in a statistically significant manner in T3-T4 surgically resected patients were tVSA and qVSA. Instead, two parameters increased in a statistically significant manner in T3-T4 surgically resected patients: FCR and SHI. Again, none of the above-mentioned parameters was altered in a statistically significant manner in early tumor stage resected patients, regardless of the gender. CONCLUSION. For the first time, we used a series of newly developed formant parameters, introduced by various authors for the study of the articulatory undershoot of the tongue in various neurodegenerative diseases. The statistical analysis of our results highlighted in an incontrovertible way a strong correlation and significance of each of our parameters F2 / i / / F2 / u /, FCR, tVSA, qVSA, with the entity of the TNM, and therefore of the surgical extension of the resection, and in parallel with the loss of the intelligibility of the speech that proportionally reaches higher values in the advanced stages of the disease as can be deduced from the SHI trend.
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Huang, Huai-Hsuan, Fei-Yuan Hsiao, Ho-Min Chen, Chen-Yu Wang, Hwei-Fang Tien, and Bor-Sheng Ko. "Anti-Viral Prophylaxis for Hepatitis B Virus Is Associated with Improved Outcome in Patients with Diffuse Large B Cell Lymphoma in Taiwan - a Population-Based Study between 2011 and 2015." Blood 134, Supplement_1 (November 13, 2019): 4765. http://dx.doi.org/10.1182/blood-2019-127972.
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Background: Rituximab increases the possibility of reactivation of hepatitis B virus (HBV) in patients with diffuse large B cell lymphoma (DLBCL), which is the most common non-Hodgkin lymphoma worldwide. Managing HBV during the treatment for DLBCL is therefore a particularly important issue in HBV endemic area, such as Taiwan. However, there is no population-based study to investigate whether HBV status and antiviral prophylaxis influence the survival in DLBCL patients. Objective: To evaluate the impact of HBV status and antiviral prophylaxis on survival in DLBCL patients, we incorporated the data from the Taiwan Cancer Registry Database (TCRD), the National Health Insurance Research Database (NHIRD), and the National Death Registry in our study. Methods: From TCRD, we identified 6304 patients with newly diagnosed DLBCL between 2011 and 2015. Patients were excluded if they were younger than 20 years (n=52), had unknown Ann Arbor stage (n=277), had other cancers before the diagnosis of DLBCL (n=336), or did not receive any treatment for DLBCL (n=514). We also excluded patients treated with regimens other than R-CHOP, R-CVP, CHOP, or CVP (n=711), with unknown HBV (n=492) or hepatitis C virus (HCV, n=152) status, or treated with antiviral therapies but not HBV or HCV carriers (n=65). There were 3702 DLBCL patients treated by R-CHOP, R-CVP, CHOP, or CVP for survival analysis, including 781 HBV carriers. Results: According to the HBV status and the applications of antiviral prophylaxis, we stratified patients into three groups, HBsAg-negative patients (HBV-neg, n=2921), HBV carriers with antiviral prophylaxis (HBV+Tx, n=711), and HBV carriers without antiviral prophylaxis (HBV+No, n=70). The baseline characteristics were similar between the three groups, except that HBV+Tx patients were younger than others (median age: 63.7 years in HBV-neg patients, 57.0 years in HBV+Tx ones, and 62.9 years in HBV+No ones). HBV+Tx patients tended to receive R-CHOP, which was the standard frontline regimen for DLBCL patients (78.2% in HBV-neg patients, 87.5% in HBV+Tx ones, and 77.1% in HBV+No ones). The most frequent used antiviral agent was entecavir (91.0%). In survival analysis, the median overall survival (OS) of HBV-neg patients was 74.23 months, similar to that of HBV+Tx patients (median OS was not reached). However, the median OS of the HBV+No patients was only 35.61 months (P=0.0028 when compared with HBV+Tx patients), which indicated the antiviral prophylaxis improved OS in DLBCL patients with HBV infection. In the multivariate analysis of OS, we included other potential prognostic factors in DLBCL patients, such as gender difference, age, Carlson comorbidity index, Ann Arbor stage, type of frontline chemotherapies for DLBCL, radiotherapy in the frontline therapy, and the practice setting (medical centers or others). The status of HBV and antiviral prophylaxis was still an independent prognostic factor in the multivariate analysis of OS (hazard ratio and 95% confidence interval: 1 for HBV-neg, 1.01 (0.88-1.16) for HBV+Tx, and 1.70 (1.22-2.35) for HBV+No; P=0.0069). Conclusion: From our population-based study, we illustrated the importance of antiviral prophylaxis in the DLBCL patients with HBV infections. HBV carriers would have similar survival to the HBV-negative patients if they received antiviral prophylaxis for HBV infections. Figure Disclosures Tien: Daiichi Sankyo: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Johnson &Johnson: Honoraria; Novartis: Honoraria; Roche: Research Funding; Alexion: Honoraria; Celgene: Research Funding; Roche: Honoraria; BMS: Honoraria.
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Ko, Bor-Sheng, Grace Hui-Min Wu, Yu-Chiao Wang, Ming Yao, Churn-Shiouh Gau, Szu-Chun Hsu, Jih-Luh Tang, and Raoh-Fang Pwu. "Demographics and Long-Term Outcome of Incident Immune Thrombocytopenic Purpura: A Twelve-Years Nationwide Population-Based Study in Taiwan." Blood 126, no. 23 (December 3, 2015): 3259. http://dx.doi.org/10.1182/blood.v126.23.3259.3259.
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Abstract Background and Objectives Immune thrombocytopenic purpura (ITP) is a rare disease, and the epidemiology and long-term outcome are still rarely characterized. This study is then aimed to provide a population-based assessment for the demographics and outcome about ITP in Taiwan, an island in Southeastern Asia with around 23 million inhabitants. Material and Methods This study used claims data from Taiwan's National Health Insurance Research Database (NHIRD). The database included information from a nationwide, mandatory-enrollment and single-payer healthcare system with more than 99% coverage rate in Taiwan since March, 1995. To address adequate medical history tracking and outcome follow-up, only those patients with the first ITP diagnosis from Jan 1st, 2001 to Dec 31st, 2012 were included. Incident ITP was identified first with ICD-9 codes; but those cases with codes for potential ITP-confounding diseases within 6 months from the first ITP code were excluded. Next, only those patients with meaningful pharmacological treatment or splenectomy within 3 months were included in the final analysis. Chronic ITP was defined for those with ICD-9 ITP codes and continuous drug exposure for more than 3 months, or with rituximab or splenectomy. Sex- and age-matched cohorts with 1:10 ratio were selected from Taiwan general population for survival comparison. Results Of the 30673 patients with ITP codes from Jan 1st, 2001 to Dec 31st, 2012, 11437 were identified as incident ITP. The mean age was 42.9+/-27.5 y/o, and 5445 (47.6%) cases had Charlson Comorbidity Index (CCI) score more than 2. The average incidence was 4.16 per 100,000 person-year, and the details are shown in Table 1. The incidence for female was higher than that for male (4.97 vs. 3.38 per 100,000 person-year), and the incidences across the age represented a U-shape distribution, with the highest ones in those aged 0-9 y/o and more than 70 y/o (7.21 and 13.3 per 100,000 person-year, respectively). Some geographic distribution of the incidences existed, with the highest in central part and the lowest in Eastern part of Taiwan (5.33 and 2.64 per 100,000 person-year, respectively). Secondary causes could be identified in 3560 (31.0%) cases, and malignant neoplasma (1743, 49.0%) were most frequently noted. Viral hepatitis B or C were found in 785 (22.1%) cases. Chronic ITP was diagnosed during follow-up in 29.1% (n=3324) of incident ITP patients. Those incident ITP patients aged 0-9 y/o (431/2169 vs. 2893/9268, p<0.001) or male gender (1118/4697 vs. 2206/6740, p<0.001) had a less chance to develop chronic ITP. As compared with the matched cohort from general population, the 10-yr survival rate was significantly inferior for all ITP patients, no matter in those aged below 20 y/o (96.9+/-0.5% vs. 98.8+/-0.1%, p<0.0001) or above 20 y/o (62.5+/-0.8% vs. 83.2+/-0.2%, p<0.0001), as in Figure 1. For chronic ITP, the disadvantaged 10-yr survival rates persisted (for age below 20 y/o: 96.5+/-1.0% vs. 98.6+/-0.2%, p<0.0001; for age above 20 y/o: 72.7+/-1.3% vs. 86.7+/-0.4%, p<0.0001, as in Figure 2). Elder age, male gender and high CCI scores predicted worse survival in multi-variate analysis. Conclusions This study is the largest population-based epidemiology report at nationwide scale till now. Not only the results can provide a valuable demographic description for ITP in Eastern Asia, but also they confirm an inferior long-term outcome for ITP patients, which necessitates more attention to their health care. SD: standard deviation Table 1. Table 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Tang: Novartis: Consultancy, Honoraria.
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Welch, Ryan M., Jacqueline H. R. DeMeritt, and Courtenay R. Conrad. "Conceptualizing and Measuring Institutional Variation in National Human Rights Institutions (NHRIs)." Journal of Conflict Resolution, December 27, 2020, 002200272098234. http://dx.doi.org/10.1177/0022002720982349.
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A wealth of literature argues that domestic institutions can sometimes restrain government repression. In this article, we highlight an institution tasked specifically with protecting and promoting human rights: the National Human Rights Institution (NHRI). Although common international standards exist, NHRIs exhibit substantial variation in their organization, the rights that they protect, the activities they permit, and the manner in which they appoint their members. Scholarship to date has conceptualized and measured NHRIs dichotomously; an NHRI either exists or it does not. We present data that highlights NHRI heterogeneity collected via content analysis of NHRI annual reports, NHRI websites, national constitutions, government legislation, and other sources. Using these data, we show NHRIs that can publish their findings and NHRIs that can punish offenders are each associated with less state torture. These data will allow future researchers to better explore important questions regarding NHRI origins, design, processes, and effectiveness.