Artykuły w czasopismach na temat „946/.72”

Ba2TiO4 and Ba4Ti13O30 Thick Films Were Prepared by Laser Chemical Vapor Deposition Using Ba- and Ti-Dipivaloylmethanate Precursors. Single-Phase Ba2TiO4 Thick Films Were Obtained at 845–946 K and Ba/Ti Source Molar Ratio 2.4. Single-Phase Ba4Ti13O30 Films Were Obtained at 944–1011 K and Ba/Ti Source Molar Ratio 0.38. Ba2TiO4 Thick Films Consisted of Truncated Grains, while Ba4ti13o30 Thick Films Had Shellfish-Like Grains. Ba2TiO4 and Ba4Ti13O30 Thick Films Showed a Columnar Growth and their Deposition Rates Were 72 and 132 μm h−1, Respectively.

644 Background: The concept of treatment to disease progression must be tempered by the potential for cumulative toxicities of ongoing therapy. Data suggest that treatment holidays may provide improved quality of life without significantly compromising outcomes in metastatic disease. Our aim was to characterize the frequency of intermittent and stop-and-go strategies in a population-based cohort of mCRC patients. Methods: Patients diagnosed with mCRC and who received any palliative systemic treatment at the British Columbia Cancer Agency from Jan 2008 to Dec 2010 were identified from the provincial pharmacy database. First-line (1L) and second-line (2L) therapy choices, duration on each line of therapy, and number of treatment holidays, defined as any time interval of >/= 4 weeks without any therapy, were characterized. Results: In total, 946 patients were identified: median age was 64 (IQR 55-72) years, 521 (55%) were men, and 626 (66%) had colon cancer. In 1L treatment, the majority received combination systemic therapy: 474 (50%) FOLFIRI +/- bevacizumab (B), 224 (24%) FOLFOX +/- B, and 248 (26%) 5-FU/capecitabine. The median number of cycles on 1L therapy was 9 (IQR 4-13). Treatment holidays were common with 302 (32%) patients experiencing at least one break, each lasting a median of 49 (IQR 36-99) days. Compared with no B, 1L patients treated with B received more therapy (median 12 [IQR 8-20] vs 8 [IQR 4-12] cycles). However, they were also more likely to undergo a treatment holiday (34% vs 31%), but the duration of each break was shorter (median 49 [IQR 36-92] vs 56 [IQR 35-119] days). Only 312 (33%) out of the 946 patients proceeded to 2L therapy. The median interval between stopping 1L and starting 2L was 43 (IQR 20-162) days. Compared with 1L, the median number of treatment cycles was shorter in 2L (median 7 [IQR 4-12]). Treatment holidays were also less frequent with only 50 (16%) out of 312 patients experiencing at least one break, each lasting a median of 56 (IQR 38-100) days. Conclusions: The use of the stop-and-go approach was prevalent in this population-based cohort of mCRC patients. The relationship between intermittent treatment and outcomes will be presented at the meeting.

Background and aims: Synthetic organophosphates (OPs) inhibit acetylcholinesterase resulting in the accumulation of acetylcholine, failure of organs, and eventually death. Diisopropyl-fluorophosphatase (DFPase) is one of the OPs degrading enzymes that has broad substrate from OPs. In this study, for the first time, the secretory expression of DFPase in Bacillus subtilis was investigated in order to accelerate the biodegradation rate of OPs. Methods: DFPase gene was amplified using polymerase chain reaction (PCR) from the pET28-inaV/N-dfpase plasmid. The PCR product was subcloned in the pWB980 plasmid. Competent B. subtilis WB600 were transformed with recombinant plasmid. SDS PAGE technique was used to study the expression of protein secreted in superrich medium. Results: Appearance of the 946 bp band in agarose gel after digestion of transformed plasmid confirmed the presence of DFPase gene in this construct. Approximately, 35 kDa protein band was shown in culture medium after incubating at 35°C for 72 hours and 150 rpm. Measurement of enzyme’s activity was done by monitoring the release of fluoride from diisopropyl fluorophosphate (DFP), using ion-meter. Results showed that enzyme’s activity was 3333 U/L. Conclusion: Bacillus subtilis is a suitable host for production of secretory and active form of DFPase.

Bioenergy is one of the most important renewable-energy sources worldwide, accounting for more than two-thirds of the renewable-energy mix. Biomass accounted for 13–14% of the primary energy consumption in 2018, and by 2050, it is expected to account for 50% of the global primary energy consumption. This article studies the biomass potential in Iraq. The potential of this country to be one of the leading producers of bioenergy is discussed, remarking on the importance of agricultural crop waste. Nowadays, Iraq generates a great quantity of biomass every year. Unfortunately, instead of contributing to the energy industry and economic progress, these wastes are burned directly, potentially causing a slew of environmental issues. Based on earlier studies, the theoretical energy potential of Iraq agricultural wastes is assessed. It is concluded that 10 million tons of dry agricultural leftovers can create 115 PJ of energy per year. According to the findings of this study, 10 million heads of cattle in Iraq could generate 72 million m3 of biogas per day, with a total potential power of 946 TJ per year from animal wastes, mainly cattle dung. On the other hand, bioenergy potential is heavily reliant on the geographical distribution, availability, and accessibility of real waste. Wasit, Qadisiyah, and Mosul are the most feasible locations for this agricultural waste potential. This might lead to the development of a long-term economic plan for the successful and sustainable utilization of important accessible waste for bioenergy generation.

A 20-ml blood sample was collected from adult patients with suspected bloodstream infections and distributed equally into the four volume-controlled bottles of a blood culture set consisting of aerobic and anaerobic BACTEC Plus/F bottles and aerobic and anaerobic BacT/Alert FAN bottles. All bottles were incubated in their respective instruments for a standard 5-day protocol or until the instruments signalled positivity. Samples in all bottles with negative results by these instruments were terminally subcultured. A total of 8,390 blood culture sets were obtained during the study period, of which 4,402 (52.5%) met the study criteria. Of these, 946 (21.5%) were positive either by instrument signal or by additional terminal subculture of all negative bottles and yielded growth of microorganisms. Five hundred eighty-nine (13.4%) blood culture sets were considered to have recovered 663 clinically significant organisms. When both the BACTEC and the BacT/Alert systems were used, 465 positive sets were detected; BACTEC alone detected 52 positive sets and BacT/Alert alone detected 72 (P = 0.09). No differences were found between the two systems in microbial recovery rate from blood cultures obtained from patients on antibiotic therapy. Significantly more members of the family Enterobacteriaceae (P < 0.01) were detected from patients without antimicrobial therapy by BacT/Alert than by BACTEC. The false-negative rates were 0.20% for BACTEC and 0.32% for BacT/Alert. A significantly higher false-positive rate was found for BACTEC (P < 0.0001). Both systems were comparable for the time to detection of microorganisms. However, gram-positive bacteria were detected faster by BACTEC andEnterobacteriaceae were detected faster on average by BacT/Alert. We concluded that both systems are comparable in their abilities to recover aerobic and anaerobic organisms from blood cultures and a terminal subculture might not be necessary for either of the two systems. The increased positivity rate when using an anaerobic bottle in a two-bottle blood culture set is due to the additional blood volume rather than to the use of an anaerobic medium.

Abstract Abstract 2389 Autologous hematopoietic cell transplantation (autoHCT) is standard therapy for high-risk hematologic disorders and solid tumors. We assessed whether overall survival (OS) at Day 100, which represents early transplant-related mortality (TRM), and at one year, which represents disease-related mortality and later TRM, had changed over time. The study population was derived from patients undergoing 68,404 first autoHCTs between 1994–2005 in US and Canadian centers reported to the CIBMTR. Statistical significance was measured using Ptrend over 6 time cohorts to test whether the OS estimates were stable (slope = 0), increasing (slope>0) or decreasing (slope<0) over time. The Day 100 and 1-year OS estimates are shown in the Table. Disease and disease status subgroups were defined a priori, and the OS estimates are not adjusted for any covariates such as age, Karnofsky status, etc. Mortality rates at Day 100 were, in general, low for all diseases examined and improved significantly over time for NHL in complete remission (CR) 2/sensitive 1st relapse, for lymphoma in primary induction failure (no prior complete remission) and myeloma in first partial or complete remission. Improvements in 1-year OS were seen for NHL in CR1/sensitive 1st relapse and myeloma in remission at the time of transplant. OS has improved for many patients undergoing autoHCT which likely reflects improvement in supportive care and better patient selection. Day 100 mortality rates in autoHCT patients treated during the most recent period 2004-5 are as low as 2–5% in patients with chemotherapy sensitive disease pre-autoHCT. Even in patients transplanted with resistant disease (no prior CR), the Day 100 mortality rate is only 5% in MM and 9% in HL/NHL patients. Although the 1-year OS has improved over time there is still a significant decline in OS between the Day 100 and 1-year time points, especially for patients with NHL in CR2/sensitive 1st relapse, lymphoma in primary induction failure and myeloma not in remission, suggesting a need for improved disease control in these patients. Table 1: Overall survival (95% CI) estimates over time. Autologous HCT 1994-5 1996-7 1998-9 2000-01 2002-3 2004-5 Ptrend NHL in CR2/Rel 1 sens N 890 1067 1041 1020 946 1116 <0.001 @100 days 89 (87–91) 90 (88–92) 90 (88–92) 94 (92–95) 94 (92–95) 95 (94–97) <0.001 @1 year 68 (65–71) 69 (66–72) 72 (69–75) 77 (75–80) 78 (75–80) 80 (77–83) HL in CR2/Rel1 sens N 384 384 466 435 477 573 0.4758 @100 days 95 (92–97) 95 (92–97) 96 (94–97) 97 (95–98) 96 (94–98) 97 (95–98) 0.1985 @1 year 86 (82–89) 87 (84–91) 87 (83–90) 89 (85–92) 90 (87–93) 91 (88–93) HL or NHL in PIF N 647 708 772 895 570 504 0.0299 @100 days 86 (84–89) 88 (86–90) 87 (84–89) 90 (87–92) 90 (88–93) 91 (89–94) 0.7532 @1 year 69 (65–73) 69 (65–72) 70 (67–74) 72 (68–75) 71 (67–75) 72 (67–76) MM in CR1/PR1/PIF sens N 267 541 718 1567 2423 3192 <0.001 @100 days 96 (94–98) 96 (94–98) 96 (94–97) 97 (96–98) 98 (97–98) 98 (98–99) <0.001 @1 year 83 (79–88) 84 (81–87) 87 (85–90) 90 (89–92) 92 (91–93) 92 (91–93) MM in less than PR N 105 177 392 420 521 586 0.3829 @100 days 92 (85–96) 94 (90–97) 96 (94–98) 96 (94–98) 97 (95–98) 95 (93–97) 0.0857 @1 year 79 (70–87) 79 (73–85) 86 (82–89) 88 (84–91) 88 (85–91) 87 (84–90) NHL – non-Hodgkin lymphoma, HL – Hodgkin lymphoma, MM – myeloma, CR – complete remission, Rel – relapse, PIF – primary induction failure, sens – sensitive Disclosures: No relevant conflicts of interest to declare.

9510 Background: From 2/2001 to 2/2002, 946 patients (pts) with advanced GIST were randomized to IM at two dose levels within a controlled EORTC/ISG/AGITG trial. This analysis investigates whether achievement of an objective response, according to the RECIST criteria, has any predictive value for time to progression (TTP) and overall survival (OS). Methods: According to the protocol, the 3 first disease measurements were foreseen at 2, 4, and 6 months (m). Results of those measurements were classified in 6 categories: PR (>30% reduction of the tumor load), MR (10–30% reduction), NC- (0–10% reduction), NC+ (0–20% increase), PD (> 20% increase or new lesions), and subjective PD (clinical PD, no measurements). Pts included the analyses were those still followed at the measurement point, who had not previously progressed. Results: A total of 906 pts had measurable disease at entry; from those, 852 were evaluable at 2 m, 681 at 4 m and 642 at 6 m. At all measurement time points, PR and MR resulted in similar TTP and OS; this was also true for NC- and NC+, and for PD and subjective PD. As an example, for the evaluation at 4 m, the median TTP was respectively 2.50, 2.55, 1.86, 1.65, 0.31 and 0.30 years in the 6 groups of pts, while the 3 years OS estimate were 71%, 72%, 57%, 56%, 32% and 0%. Pts were subsequently classified as responders (more than 10% reduction of the tumor load), no change (less than 10% reduction and less than 20% increase) and PD (> 20% increase, new lesions or clinical PD). This new response category is highly predictive of further progression or survival, for the 2 first measurements points, and in both therapeutic arms, but pts stable at 6 m had the same survival as responders at 6 m. In addition, RECIST response documented at 2, 4 and 6 m resulted in similar TTP and OS. Conclusions: The RECIST criteria are only optimal for identifying IM-resistant GISTs (PD > 20%) and not adequate for the evaluation of IM efficacy. All pts exhibiting at least a 10% reduction (until complete response) of the tumor load have to be considered as responders to IM (IM-sensitive GISTs). A real stabilisation of the disease consisting in a less than 10% tumor reduction and a less than 20% tumor increase identifies pts who have an intermediate sensitivity to IM. [Table: see text]

Beta-lactamase was purified from local isolate Klebsiella pneumonia by several steps included precipitation with ammonium sulphate at 20-40% saturation, DEAE- ion exchange chromatography and gel filtration on Sephacryl S-200 column. The obtained purification fold and recovery were 32.66; 47.04% respectively. The characterization of the purified beta-lactamase showed that the molecular weight was about 4000 daltons as determined by gel filtration.Purified enzyme had an optimal pH of 7 for activity and an optimal stability between pH 6.5-7.5, results shows that the optimal temperature appear to be 35 ? C .During storage the enzyme retained 72% at -20 ? C and retained 25% of the activity at the same period at 4 ? C.

<b><i>Introduction:</i></b> Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder characterized by progressive deterioration of motor neurons. Assessment of the size/geographic distribution of the ALS population, including ALS with genetic origin, is needed to understand the burden of the disease and the need for clinical intervention and therapy. <b><i>Objectives:</i></b> The main objective of this study was to estimate the number of prevalent and incident ALS cases overall and superoxide dismutase 1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) ALS in 22 countries across Europe (Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, and UK), North America (USA and Canada), Latin America (Argentina, Brazil, Colombia, Mexico, and Uruguay), and Asia (China, Japan, South Korea, and Taiwan). <b><i>Methods:</i></b> A comprehensive literature search was conducted to identify population-based studies reporting ALS prevalence and/or incidence rates. Pooled prevalence and incidence rates were obtained using a meta-analysis approach at the country and regional geographic level. A country-level pooled estimate was used when ≥2 studies were available per country and geographic regional pooled estimates were used otherwise. The proportion of cases with a SOD1 or C9orf72 mutation among sporadic (sALS) and familial (fALS) cases were obtained from a previous systematic review and meta-analysis. <b><i>Results:</i></b> Pooled prevalence rates (per 100,000 persons) and incidence rates (per 100,000 person-years) were 6.22 and 2.31 for Europe, 5.20 and 2.35 for North America, 3.41 and 1.25 for Latin America, 3.01 and 0.93 for Asian countries excluding Japan, and 7.96 and 1.76 for Japan, respectively. Significant heterogeneity in reported incidence and prevalence was observed within and between countries/geographic regions. The estimated number of 2020 ALS cases across the 22 countries is 121,028 prevalent and 41,128 incident cases. The total estimated number of prevalent SOD1 cases is 2,876 cases, of which, 1,342 (47%) were fALS and 1,534 (53%) were sALS, and the number of incident SOD1 cases is 946 (434 [46%] fALS and 512 [54%] sALS). The total estimated number of prevalent C9orf72 cases is 4,545 (1,198 [26%] fALS, 3,347 [74%] sALS), and the number of incident C9orf72 cases is 1,706 (450 [26%] fALS and 1,256 [74%] sALS). <b><i>Discussion:</i></b> The estimated number of patients with SOD1 and C9orf72 ALS suggests that although the proportions of SOD1 and C9orf72 are higher among those with fALS, the majority of SOD1 and C9orf72 ALS cases may be found among those with sALS (about 53 and 74%, respectively). These results suggest that classification of fALS based on reported family history does not capture the full picture of ALS of genetic origin.

Abstract Background The median age at diagnosis of MM is 69 years. Randomized, controlled studies on the safety and effectiveness of AHCT are lacking in those > 70 years of age and many patients are considered “ineligible” on the basis of age. We analyzed survival (OS) outcomes of 11,430 MM patients from US and Canada receiving AHCT after high dose melphalan (MEL) between 2008 -2011 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The relative efficacy of AHCT was compared in 3 cohorts; those aged ≥70 years (Cohort 1, n=946) vs. those 60-69 years (Cohort 2, n= 4666) and vs. 18-59 years (Cohort 3, n=5818). A statistically representative subset of 1279 patients was then analyzed in further detail to compare relapse, progression free survival (PFS) and non-relapse mortality (NRM). Results The median ages in group 1, 2, and 3 were 72, 64 and 53 years, respectively with an upper age of 89 years. The older age cohort 1 was composed of a higher proportion of male patients, IgA MM, US patients (vs. Canada) and had worse Karnofsky scores (KPS < 100) and co morbidity scores (HCTCI ≥ 2), (all p values <0.05). The older age cohort was less likely to be transplanted within the first year of diagnosis and more likely to have MEL dose reduction (MEL <180 mg/m2 in 42%). Disease status at AHCT did not vary between groups with >40% of patients at least in a very good partial remission (≥VGPR) at transplant in all 3 cohorts. After a median follow up in survivors of 2 years, median OS has not been reached and 3 year OS was inferior for the older cohort at 72% (95% CI, 67-76%), 75% (73-77%), 78% (76-79%) in cohorts 2 and 3 respectively (Figure 1). In multivariate analysis, increasing age was associated with inferior OS (p=0.0006, Fig 1). Hazard ratio for death was 1.12 for cohort 2 vs. 3, 1.35 for cohort 1 vs. 3 and 1.2 for cohort 1 vs. 2. Other significant predictors of lower OS were higher HCTCI score, lower KPS, longer (>12mo) interval from diagnosis to AHCT and inferior disease status (<VGPR) at AHCT. Further analyses were performed to identify the contribution of relapse, NRM and post relapse survival. NRM within the first year was 0% for the older cohort and 2% for the other 2 cohorts, likely reflecting careful patient selection. Relapse risk at 3 years was similar between cohorts 1,2 and 3 at 63% (48-74%), 51% (55-66%) and 56% (51-60%) respectively. PFS at 3 years was 33% (21-46%), 38% (33-43%) and 42% (37-46%) respectively. In multivariate analyses, increasing age was NOT associated with higher risk of relapse, NRM or lower PFS. KPS <80 was associated with higher risk of relapse, NRM and lower PFS. Other significant risks for relapse and lower PFS were longer interval from diagnosis to AHCT and a < VGPR disease state prior to AHCT. Post relapse survival was significantly worse for the older cohort (p=0.03, Figure 2). Post relapse survival was significantly worse with increasing age. For cohorts 1, 2 and 3 at 2 years, it was 54% vs. 50% and 63% and at 3 yrs 25% vs. 37% and 49% respectively (p=0.03, Fig 2). Conclusions AHCT although performed less frequently in the older MM patient, offers equivalent efficacy in and is associated with low NRM. Survival differences are driven partly by higher co-morbidities and lower post relapse survival. Myeloma related outcomes are similar when appropriate older patients are treated with aggressive therapy. Disclosures: Gasparetto: Onyx: Membership on an entity’s Board of Directors or advisory committees; Millennium (2012): Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Celgene ( 2012): Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lonial:Sanofi: Consultancy; BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Millennium: Consultancy; Onyx: Consultancy. Hari:Celgene: Consultancy; Onyx: Consultancy.

The purpose of this report was to examine the effects of physical education acrobatic activities as a function of individual differences on approach-avoidance tendencies for acrobatics. The data of a study conducted by Robazza, Bortoli, Carraro, and Bertollo (2006) were analyzed after having classified students as high- or low-avoiders. Approach-avoidance tendencies and idiosyncratic emotions related to acrobatic tasks and adventurous sports were originally assessed for 72 Italian male high school students. Experimental participants engaged in acrobatic tasks of physical education for 12 lessons, while control participants were involved in team sports. Analysis showed that high-avoiders changed their emotions positively toward physical education tasks more than low-avoiders, whereas the latter modified their attitudes for adventurous sports. Approach-avoidance tendencies can be expected to moderate involvement in challenging physical activities.

BackgroundRheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) are characterized by a deterioration of bone mass, bone microstructure and biomechanics [1, 2]. However, little evidence is available on the long-term evolution of these bone properties and the impact of autoimmunity, disease activity and targeted anti-inflammatory therapy.ObjectivesTo evaluate the longitudinal course of peripheral volumetric bone mineral density (vBMD), microstructure and biomechanics in patients with seropositive RA (RA+), seronegative RA (RA-) and PsA (i) by diagnosis (ii) disease activity and (iii) ever use of biologic/targeted synthetic (b/ts) DMARDs.MethodsRA+, RA-, PsA patients who had at least one high-resolution CT scan were included. Prospectively collected longitudinal data from the distal radius. vBMD, microstructure and biomechanical properties were assessed and data on treatments and disease activity (DAS-28) were collected. We described and summarized the time course of these measurements, using linear regression models as age and sex adjusted time-conditional means and mean differences by disease category, time-varying weighted average disease activity and intervening b/tsDMARD treatments.ResultsWe analyzed 946 scans from 412 patients (193 RA+, 68 RA-, 151 PsA) with a median CT follow-up duration of 24 months (IQR 0 to 47). (Table 1). Overall, bone quality showed a downward course over time. RA+ patients showed lower total and trabecular bone densities compared to patients with psoriatic arthritis throughout the time course. (Figure 1a). RA+ patients also showed decreasing trabecular number with increasing trabecular thickness, trabecular irregularity and trabecular separation over time in comparison to PsA (Figure 1 b) suggesting a gradual disappearance of the thinner trabeculae. We detected significant time/DAS-28 interactions in PSA patients indicating faster cortical bone loss over time with increasing DAS-28 (p interaction =0.049), in RA- patients showing faster trabecular bone loss over time with higher disease activity (p.interaction 0.044) and in RA+ patients for trabecular density (p interaction 0.038), bone stiffness (p interaction 0.022) and failure load (p interaction 0.034) indicating a faster deterioration of bone quality over time with increasing disease activity. Interestingly, RA+ patients exposed to b/tsDMARDs had numerically lower bone density compared to unexposed patients, whereas the temporal pattern suggested a more stable vBMD over time as opposed to a deteriorating pattern in the unexposed. However, the uncertainty in these analyses was large and none of the time-exposure interactions or pairwise differences over time between ever vs. never exposed categories were significant.ConclusionAutoimmunity impairs bone health over time and is particularly associated with impaired trabecular bone quality. Good control of disease activity in RA+, RA-, and PsA patients may be helpful in preventing bone loss and deterioration of bone microstructure, and biomechanics. Specific contribution of b/tsDMARDs to the time course of bone quality at the radius needs further clarification.References[1]Kocijan R et al. J Bone Miner Res 2015[2]Stemmler F et al. Ann Rheum Dis 2018Table 1.Patient characteristicsDiagnosisPsARA seronegativeRA seropositiveN15168193Age, years, mean (SD)51.7 (12.2)58.8 (12.2)53.9 (12.5)Females, n(%)72 (47.7)49 (72.1)131 (67.9)Disease duration, years median (IQR)3.0 (1.0-10.0)3.0 (1.0-8.0)5.0 (0.0-13.0)Follow-up duration, months, median (IQR)24.7 (0.0-48.0)16.4 (0.0-42.7)25.2 (0.0-47.9)No of scans, n (%) 148 (31.8)21 (30.9)50 (25.9) 256 (37.1)29 (42.6)56 (29.0) 331 (20.5)12 (17.6)49 (25.4) >416 (10.6)6 (8.8)38 (19.7)Glucocorticoid use, n (%)57 (37.7)52 (76.5)149 (77.2)csDMARDs use, n (%)24 (15.9)25 (36.8)59 (30.6)b/tsDMARDs use, n (%)127 (84.1)43 (63.2)134 (69.4)Figure 1.Time course of bone density (A) and microstructure (B) in patients with PsA and RA.AcknowledgementsThe study was supported by the Deutsche Forschungsgemeinschaft (FOR2886 PANDORA, CRC1181, CRC1483 EmpkinS). Additional funding was received by BMBF (project MASCARA), the ERC Synergy grant 4D Nanoscope, and the IMI funded projects RTCure and HIPPOCRATES, and the 2022 GRAPPA Pilot Research Grant (DS).Disclosure of InterestsNone Declared.

Nghiên cứu sử dụng phương pháp hồi cứu để xác định nguyên nhân gây viêm phổi bệnh viện và khả năng kháng kháng sinh của các vi khuẩn phân lập được tại khoa Hồi sức tích cực Bệnh viện Trung ương Thái Nguyên, năm 2020 - 2021. Kết quả: Trong 467 mẫu có 30,5% (145/467) mẫu bệnh phẩm phân lập được tác nhân gây bệnh, đờm chiếm tỷ lệ 45,8% (66/145), máu 28,3% (41/145), dịch màng phổi 11,8% (17/145), dịch nội khí quản 6,3% (9/145). Vi khuẩn phân lập được: P. aeruginosa 22,1% (32/145), K. pneumoniae 19,3% (28/145), A. baumannii 17,9 (26/145), E. coli 15,2% (22/145), và S. aureus 9,7% (14/145). Mức độ kháng kháng sinh: A. baumannii kháng với các kháng sinh được thử nghiệm từ 50 – 100%, chưa kháng colistin. E. coli và K. pneumoniae kháng kháng sinh nhóm beta lactam (> 80%), nhóm quinolon > 70%, P.aeruginosa kháng các kháng sinh: Ceftazidime, Gentamicin, Levofloxacin, Ofloxacin từ 51,7 – 53,8%. S. aureus đề kháng hoàn toàn với kháng sinh Penicillin G (100%), đề kháng nhóm Macrolid từ 72 – 87,5%, chưa kháng Vancomycin. Kết luận: Căn nguyên gây viêm phổi bệnh viện chủ yếu là P.aeruginosa, K. pneumoniae, A. baumannii, E. Coli, S. aureus. Các vi khuẩn phân lập được có tỷ lệ kháng kháng sinh cao và đa kháng thuốc, A.baumannii chưa kháng lại Colistin và S.aureus chưa phát hiện kháng Vancomycin.

Abstract Background: Numerous recurrent chromosomal abnormalities have been described in adult Ph-negative ALL, often observed in small patient cohorts. In the largest MRC/ECOG study (Moorman, Blood 2007), t(4;11)(q21;q23), 14q32 involvement, complex karyotype (≥5 abnormalities), and low hypodiploidy/near triploidy (Ho-Tr) were associated with shorter event-free survival (EFS), while patients with high hyperdiploidy or del(9p) had a better outcome. We aimed to confirm these observations in 955 adult patients (15-60y; median, 35y) with Ph-negative ALL treated in the pediatric-inspired GRAALL-2003/2005 trials. Patients and Methods: Overall, a karyotype was performed for 946 (611 BCP-ALL, and 335 T-ALL), successful for 811 (523 BCP-ALL and 288 T-ALL) and abnormal in 590 patients (387 BCP-ALL and 203 T-ALL). FISH and/or PCR screening for relevant abnormalities and DNA index were also performed, finally allowing for the identification of cytogenetic abnormalities in 677/955 patients (71%). All were centrally reviewed. Ultimately, 857/955 patients (90%; 542 BCP-ALL and 315 T-ALL) could be classified in 18 exclusive primary cytogenetic subsets as detailed below. Endpoints were cumulative incidence of failure (CIF, including primary refractoriness and relapse) and EFS. With a median follow-up of 4 years, 5-year CIF and EFS were estimated in these patients at 31% and 51%, respectively. As some abnormalities, including MLL rearrangements, Ho/Tr, t(1;19)(q23;p13)/TCF3 and complex karyotypes were used to stratify allogeneic stem cell transplantation (SCT) in GRAALL trials, some comparisons were repeated after censoring patients transplanted in first CR at SCT time. Results: The 542 informative BCP-ALL patients were classified as: t(4;11)(q21;q23)/MLL-AFF1 (n=72; 13%); other MLL+ 11q23 abnormalities (n=11; 2%); t(1;19)(q23;p13)/TCF3-PBX1 (#28; 5%); Ho/Tr (n=33; 6%); high hyperdiploidy (n=36; 7%); abnormal 14q32/IGH translocation (n=27; 5%); t(12;21)(p13;q22)/ETV6-RUNX1 (n=2; 0.4%); iAMP21 (n=3; 0.6%); other abnormalities (n=210; 39%); and no abnormality (n=120; 22%). The 315 informative T-ALL patients were classified as: t(10;14)(q24;q11)/TLX1 (n=64; 20%); other 14q11 or 7q34/TCR (n=31; 10%); t(5;14)(q35;q32)/TLX3 (n=29; 9%); t(10;11)(p12;q14)/PICALM-MLLT10 (n=14; 4%); deletion 1p32/SIL-TAL (n=18; 6%); MLL+ 11q23 abnormalities (n=6; 2%); other abnormalities (n=93; 30%); and no abnormalities (n=60; 19%). A complex karyotype was observed in 27/527 (5%) BCP-ALL and 21/298 (7%) T-ALL patients and a monosomal karyotype (as per Breems, JCO 2008) in 82/518 (16%) BCP-ALL and 26/286 (9%) T-ALL patients. In BCP-ALL, trends towards higher CIF and shorter EFS were observed in t(4;11) patients, with or without SCT censoring (HRs, 1.34 to 1.64; p values <0.10). Shorter EFS was observed in 3 subsets: 14q32 (HR, 2.10; p=0.002), Ho/Tr (HR, 1.45; p=0.10), and monosomal karyotype (HR, 1.42; p=0.029), but CIF were not different. This might be related to the older age of patients in these subsets (medians, 43y, 53y and 44y; p=0.029, <0.001 and <0.001, respectively) and worse treatment tolerance. For instance, higher incidences of non ALL-related deaths were observed in patients with 14q32 abnormalities or monosomal karyotype (p=0.031 and 0.067, respectively). Patients with high hyperdiploidy only tended to have lower CIF and longer EFS. Complex karyotype did not impact CIF and EFS, even after SCT censoring. Conversely, in T-ALL, complex karyotypes were associated with shorter EFS (HR, 2.20; p=0.004), even if the difference in CIF did not reach significance. A worse outcome was also observed in patients with t(10;11)(p12;q14)/PICALM-MLLT10 (HR, 2.45 and 2.14; p=0.016 and 0.021, for CIF and EFS respectively). A longer EFS was observed in patients with t(10;14)(q24;q11)/TLX1 (HR, 0.55; p=0.014), with a trend for lower CIF (HR, 0.59; p=0.070), while no inferior outcome was observed in t(5;14)(q35;q32)/TLX3 patients. Conclusion: These results show that, in the context of an intensified pediatric-inspired protocol designed for adult Ph-negative ALL patients, few cytogenetic subsets remained reliably predictive of response to therapy. Differences observed in EFS might partly be due to treatment-related mortality. Combining cytogenetics, molecular genetics and minimal residual disease monitoring could allow for better individual risk assessment (Beldjord, Blood 2014). Disclosures No relevant conflicts of interest to declare.

Background:Patients with psoriatic arthritis (PsA) require long-term treatment, which may lead to adverse events (AEs). Ixekizumab, an interleukin-17A antagonist, is approved for the treatment of adults with active PsA.Objectives:We report a summary of safety outcomes for patients enrolled in 4 PsA studies with up to 3 years of exposure to ixekizumab.Methods:This integrated safety analysis included all patients with PsA who received at least 1 dose of ixekizumab (80 mg every 2 or 4 weeks) in 4 clinical trials (NCT01695239, NCT02349295, NCT02584855, NCT03151551). Safety outcomes included treatment-emergent adverse events (TEAEs), serious AEs (SAEs), discontinuations due to AEs, deaths, and AEs of special interest.Results:A total of 1401 patients were included in this safety analysis (51.5% female; mean age 49 years), with 2247.6 patient-years of exposure (Table 1). In all, 1131 patients (80.7%) reported ≥1 TEAE (exposure-adjusted incidence rate per 100 patient-years [IR] 50.3, 95% CI 47.5–53.3), mostly mild (32.9%) or moderate (39.7%) in severity. The most common TEAEs were nasopharyngitis (n=202, IR 9.0), upper respiratory infections (n=186, IR 8.3), and injection site reaction (n=156, IR 6.9). SAEs were reported by 134 patients (IR 6.0, 95% CI 5.0–7.1). 115 (8.2%) patients discontinued due to AEs (IR 5.1, 95% CI 4.3–6.1). Six deaths were reported (IR 0.3, 95% CI 0.1–0.6). Allergic reactions/hypersensitivity were reported in 102 patients (IR 4.5, 95% CI 3.7–5.5). Three cases were adjudicated as de novo inflammatory bowel disease (IR 0.13, 95% CI 0.04–0.41); 1 was ulcerative colitis (IR 0.04, 95% CI 0.01–0.32), 2 were Crohn’s disease (IR 0.09, 95% CI 0.02–0.36). Major adverse cardiac events occurred in 12 patients (IR 0.5) and malignancies in 15 (IR 0.7), 9 of which were non-melanoma skin cancer. Opportunistic infections occurred in 40 (2.9%) patients (IR 1.8, 95% CI 1.3–2.4). Candidiasis occurred in 24 patients (oral: IR 0.7, 95% CI 0.4–1.2; oral fungal infection: IR 0.3, 95% CI 0.1–0.6; esophageal infection: IR 0.1, 95% CI 0.0–0.4). No active or reactive cases of tuberculosis were reported. Other opportunistic infections included hepatitis B (IR 0.0, 95% CI 0.0–0.3), herpes simplex (IR 1.8, 95% CI 1.3–2.5), and herpes zoster (IR 0.7, 95% CI 0.4–1.2).Conclusion:The safety profile of ixekizumab across 4 clinical trials and up to 3 years of continuous treatment in patients with active PsA was consistent with the known safety profile reported in previous studies for psoriasis and PsA. No new safety events were found in this analysis.Pooled Ixekizumab(N=1401; Total Patient-Years=2247.6)n (IR)95% CIYear 0–1(n=1401)n (IR)95% CIYear 1–2(n=946)n (IR)95% CIYear 2–3(n=510)n (IR)95% CIYear ≥3(n=89)n (IR)95% CITotal Patient-Years2247.71207.3689.8347.72.9Patients with ≥1 TEAE1131 (50.3)1050 (87.0)496 (71.9)234 (67.3)6 (206.2)47.5–53.381.9–92.465.9–78.559.2–76.592.6–458.9SAEs134 (6.0)72 (6.0)53 (7.7)19 (5.5)1 (34.4)5.0–7.14.7–7.55.9–10.13.5–8.64.8–243.9Discontinuations due to AEs115 (5.1)61 (5.1)37 (5.4)17 (4.9)0 (0)4.3–6.13.9–6.53.9–7.43.0–7.90.0–274.7Hepatic reactions112 (5.0)80 (6.6)32 (4.6)14 (4.0)0 (0)4.1–6.05.3–8.33.3–6.62.4–6.80.0–274.7Allergic reaction/hypersensitivity102 (4.5)83 (6.9)23 (3.3)5 (1.4)0 (0)3.7–5.55.5–8.52.2–5.00.6–3.50.0–274.7Serious infection28 (1.2)18 (1.5)9 (1.3)3 (0.9)0 (0)0.9–1.80.9–2.40.7–2.50.3–2.70.0–274.7Malignancies15 (0.7)4 (0.3)8 (1.2)4 (1.2)0 (0)0.4–1.10.1–0.90.6–2.30.4–3.10.0–274.7Major adverse cardiac events12 (0.5)3 (0.2)8 (1.2)1 (0.3)0 (0)0.3–0.90.1–0.80.6–2.30.0–2.00.0–274.7Inflammatory bowel disease3 (0.1)3 (0.2)1 (0.1)0 (0.0)0 (0.0)0.0–0.40.1–0.80.0–1.00.0–2.30.0–274.7 Ulcerative colitis1 (0.0)1 (0.1)1 (0.1)0 (0.0)0 (0.0)0.0–0.30.0–0.60.0–1.00.0–2.30.0–274.7 Crohn’s disease2 (0.1)2 (0.2)0 (0.0)0 (0.0)0 (0.0)0.0–0.40.0–0.70.0–1.20.0–2.30.0–274.7AE, adverse event; CI, confidence interval; IR, exposure-adjusted incidence rate per 100 patient-years; SAE, serious adverse event; TEAE, treatment-emergent adverse event.Disclosure of Interests:Carlos Sesin Speakers bureau: Amgen, AbbVie, Sanofi, Radius, Pfizer, Eli Lilly and Company, Novartis, Gaia Gallo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Amanda Gellett Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Wen Xu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Himanshu Patel Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly and Company, Glaxo Smith & Kline, Novartis, Pfizer, UCB, Bernard Combe Speakers bureau: AbbVie, BMS, Gilead-Galapagos, Eli Lilly and Company, MSD, Pfizer, Roche Chugai, Consultant of: AbbVie, Bayer, Gilead-Galapagos, Janssen, Eli Lilly and Company, Novartis, Roche Chugai, Grant/research support from: AbbVie, Eli Lilly and Company, Pfizer, Roche Chugai, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer, Consultant of: AbbVie, Janssen, Novartis, Eli Lilly and Company, MSD, Pfizer.

Social media's potential effects on well-being have received considerable research interest, but much of past work is hampered by an exclusive focus on demographics in the Global North and inaccurate self-reports of social media engagement. We describe associations linking 72 countries' Facebook adoption to the well-being of 946 798 individuals from 2008 to 2019. We found no evidence suggesting that the global penetration of social media is associated with widespread psychological harm: Facebook adoption predicted life satisfaction and positive experiences positively, and negative experiences negatively, both between countries and within countries over time. Nevertheless, the observed associations were small and did not reach a conventional 97.5% one-sided credibility threshold in all cases. Facebook adoption predicted aspects of well-being more positively for younger individuals, but country-specific results were mixed. To move beyond studying aggregates and to better understand social media's roles in people's lives, and their potential causal effects, we need more transparent collaborative research between independent scientists and the technology industry.

Abstract Objective: The aim of this study was to observe the level of alcohol-based sanitizer, mask use, and physical distancing across indoor community settings in Guelph, ON, Canada, and to identify potential barriers to practicing these behaviors. Methods: Shoppers were observed in June 2022 across 21 establishments. Discrete in-person observations were conducted and electronically recorded using smartphones. Multilevel logistic regression models were fitted to identify possible covariates for the 3 behavioral outcomes. Results: Of 946 observed shoppers, 69% shopped alone, 72% had at least 1 hand occupied, 26% touched their face, 29% physically distanced ≥ 2 m, 6% used hand sanitizer, and 29% wore masks. Sanitizer use was more commonly observed among people who wore masks and in establishments with coronavirus disease (COVID-19) signage posted at the entrance. Mask use was more commonly observed during days without precipitation and in establishments with some or all touch-free entrances. Shoppers more commonly physically distanced ≥ 2 m when they were shopping alone. Conclusions: This supports evidence for environmental context influencing COVID-19 preventive behaviors. Intervention efforts aimed at visible signage, tailored messaging, and redesigning spaces to facilitate preventive behaviors may be effective at increasing adherence during outbreaks.

BackgroundTransradial artery (TRA) access for neuroendovascular procedures is associated with fewer complications than transfemoral artery (TFA) access. This study compares hospital costs associated with TRA access to those associated with TFA access for neurointerventions.MethodsElective neuroendovascular procedures at a single center were retrospectively analyzed from October 1, 2018 to May 31, 2019. Hospital costs for each procedure were obtained from the hospital financial department. The primary outcome was the difference in the mean hospital costs after propensity adjustment between patients who underwent TRA compared with TFA access.ResultsOf the 338 elective procedures included, 63 (19%) were performed through TRA versus 275 (81%) through TFA access. Diagnostic procedures were more common in the TRA cohort (51 of 63, 81%) compared with the TFA cohort (197 of 275, 72%), but the difference was not significant (p=0.48). The TRA cohort had a shorter length of hospital stay (mean (SD) 0.3 (0.5) days) compared with the TFA cohort (mean 0.7 (1.3) days; p=0.02) and lower hospital costs (mean $12 968 ($6518) compared with the TFA cohort (mean $17 150 ($10 946); p=0.004). After propensity adjustment for age, sex, symptoms, angiographic findings, procedure type, sheath size, and catheter size, TRA access was associated with a mean hospital cost of $2514 less than that for TFA access (95% CI −$4931 to −$97; p=0.04).ConclusionNeuroendovascular procedures performed through TRA access are associated with lower hospital costs than TFA procedures. The lower cost is likely due to a decreased length of hospital stay for TRA.

Objective: To determine the prevalence of non-stenotic carotid plaques (<50%) and their association with ipsilateral strokes. Methods: Data was analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing thrombectomy with the Solitaire device. Prevalence of non-stenotic carotid plaques, ipsilateral and contralateral to the stroke was compared in patients with ESUS and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Uni- and multivariable logistic regression was performed to determine associations between non-stenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups. Results: Of the 946 patients in the database, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with ESUS (median age, 69 years) were included in the analysis.The prevalence of non-stenotic carotid plaque in the cardioembolic and ESUS subgroups was 33/226 (14.6%) and 32/141(22.7%) respectively. Bilateral non-stenotic carotid plaques were seen in 10/226(4.4%) cardioembolic and 13/141(9.2%) ESUS patients. Non-stenotic carotid plaques were significantly associated with ipsilateral strokes in cardioembolic stroke (aOR,1.91 [95% CI,1.15-3.18]) and in ESUS (aOR,1.69 [95% CI, 1.05-2.73]). Plaque irregularity, plaque hypodensity and increasing plaque thickness were significantly associated with ipsilateral stroke, only in the ESUS subgroup. Conclusion: Non-stenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and ESUS subgroups and there was increased association of hypodense plaque, increasing plaque thickness and plaque irregularity with ipsilateral stroke in the ESUS subgroup, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

Objective The aim of this study was to compare ghost ileostomy (GI) and loop ileostomy (LI) in patients undergoing oncologic resection for rectal cancer in terms of postoperative morbidity. Summary Background Data LIs are often fashioned to protect downstream anastomoses following oncologic resection for low rectal cancer at medium-to-high risk of anastomotic leak. More recently, GIs have been utilized in patients with low-to-medium risk anastomoses to reduce the rate of unnecessary stomas. Methods Medline, Embase, and CENTRAL were systematically searched. Studies investigating the use of GI in patients undergoing oncologic resection for rectal cancer were included. The primary outcomes were anastomotic leak and postoperative morbidity. Secondary outcomes included stoma-related complications and length of stay (LOS). Pairwise meta-analyses were performed with inverse variance random effects. Results From 242 citations, 14 studies with 946 patients were included. In comparative studies, 359 patients were undergoing GI and 266 patients were undergoing LI. Pairwise meta-analysis revealed no differences in the prevalence of anastomotic leak (OR 1.40, 95%CI .73-2.68, P = .31), morbidity (OR .76, 95%CI .44-1.30, P = .32), or LOS (SMD -.05, 95%CI -.33-.23, P = .72). International Study Group of Rectal Cancer anastomotic leak grades were as follows: Grade A (GI 0% vs LI 13.3%), Grade B (GI 80.9% vs LI 86.7%), Grade C (GI 19.1% vs LI 0%). Conclusions GI appears to be a safe alternative to LI following oncologic resection for rectal cancer. Larger, prospective comparative studies are warranted to evaluate the use of GI in patients deemed to be at low-to-medium risk of anastomotic leak.

Abstract Background Expression quantitative trait loci (eQTL) studies show how genetic variants affect downstream gene expression. Single-cell data allows reconstruction of personalized co-expression networks and therefore the identification of SNPs altering co-expression patterns (co-expression QTLs, co-eQTLs) and the affected upstream regulatory processes using a limited number of individuals. Results We conduct a co-eQTL meta-analysis across four scRNA-seq peripheral blood mononuclear cell datasets using a novel filtering strategy followed by a permutation-based multiple testing approach. Before the analysis, we evaluate the co-expression patterns required for co-eQTL identification using different external resources. We identify a robust set of cell-type-specific co-eQTLs for 72 independent SNPs affecting 946 gene pairs. These co-eQTLs are replicated in a large bulk cohort and provide novel insights into how disease-associated variants alter regulatory networks. One co-eQTL SNP, rs1131017, that is associated with several autoimmune diseases, affects the co-expression of RPS26 with other ribosomal genes. Interestingly, specifically in T cells, the SNP additionally affects co-expression of RPS26 and a group of genes associated with T cell activation and autoimmune disease. Among these genes, we identify enrichment for targets of five T-cell-activation-related transcription factors whose binding sites harbor rs1131017. This reveals a previously overlooked process and pinpoints potential regulators that could explain the association of rs1131017 with autoimmune diseases. Conclusion Our co-eQTL results highlight the importance of studying context-specific gene regulation to understand the biological implications of genetic variation. With the expected growth of sc-eQTL datasets, our strategy and technical guidelines will facilitate future co-eQTL identification, further elucidating unknown disease mechanisms.

Background/Objective: Punctate infarcts (PI) are increasingly seen on DWI of patients with intracerebral hemorrhage (ICH) due to small vessel disease (SVD). We aimed to determine their incidence and potential causes in a large ischemic stroke (IS) cohort that had thorough etiologic workup. Methods: Consecutive patients with MRI-confirmed IS within 72 hours of onset were enrolled. Subjects had either a single high-risk embolic source (cardioembolic or large vessel disease) or no embolic source. PIs were classified by their relationship to the primary infarct as within or outside the same vascular territory. White matter disease burden (WMDB) and microbleed counts were obtained to be used as markers of severity of SVD. Multivariable regression models were constructed to assess the association between PIs and potential etiologies (embolism vs SVD). Results: We analyzed 946 IS patients, mean age 69 +/- 15 years, 46% female. We detected PI (≤5mm) in 269 (28%) subjects, 190 (71%) within the vascular territory of the primary infarct. Large-vessel atherosclerosis (p<0.001), cardioembolic source (p<0.001), higher WMDB (p=0.032) and lower systolic blood pressure (SBP, p=0.024) were independently associated with the presence of PI. While lower SBP was associated with PI in any location (p<0.05), WMDB was only associated with PI outside the vascular territory of the primary infarct (p=0.033); and large vessel atherosclerosis was only associated with PI within the vascular territory of the primary infarct (p=0.004). Conclusions: PIs occurring within the vascular territory of a larger infarct are more likely to have a proximal embolic source, but those occurring outside are more likely related to SVD. Their relatively high incidence and diverse etiologic associations in a cohort of IS patients emphasize the importance of research into their mechanisms.

IntroductionTelemedicine use in prenatal care has greatly expanded without substantial research. Optimizing user experiences can increase telemedicine's utilization to support care access. The purpose of this study was to explore patient and provider experiences using telemedicine for routine prenatal care during the COVID‐19 pandemic, identifying factors affecting its utilization and satisfaction.MethodsIn this mixed methods study, online surveys and semi‐structured interviews with pregnant and postpartum patients and perinatal providers across the United States were used to explore experiences with telemedicine and prenatal care during the COVID‐19 pandemic. Data were collected from July to December 2021. Survey findings were analyzed using descriptive and inferential statistics, and interviews were thematically coded and analyzed, followed by mixed methods analysis.ResultsResults of 946 surveys (750 patients and 196 providers) and 30 interviews (15 patients and 15 providers) met inclusion for analysis. Telemedicine was utilized by 42% of patients and 72% of perinatal provider participants. The primary reason patients did not use telemedicine was because it was not offered. Patients and providers who did not use telemedicine expressed the following main concerns with virtual care: uncertainty about care quality, particularly when blood pressure and the fetal heart rate were not assessed, and potential challenges with developing trusting patient‐provider relationships. Patients and providers who used telemedicine rated their experience as mild to moderate satisfaction across the 6 Telehealth Usability Questionnaire domains. Satisfaction scores were not dependent on whether physical examination components were included in virtual visits.DiscussionProviding patients with the choice to use telemedicine as needed or combined with in‐person visits for routine prenatal care may increase care utilization. Although not directly linked with satisfaction, interest in using telemedicine would likely increase for patients and providers concerned with care quality if blood pressure and fetal heart rate are assessed during virtual visits.

Objective The objective of this study was to describe the acute side effects experienced by pregnant women who received a coronavirus disease 2019 (COVID-19) vaccine in the United States and to compare their experience to non-pregnant women of similar age. Study Design Adults who received a COVID-19 vaccine in the United States were invited via social media to enroll in an online, longitudinal, community-based registry (www.helpstopCOVID19.com). Participants self-reported pregnancy status, vaccination dates, manufacturer, acute side effects, impact on work and self-care, medical consultation, and hospitalization. This analysis was restricted to women aged 20 to 39 at the time of vaccination. Side effects reported by pregnant women were compared to those reported by non-pregnant women. Results This analysis included 946 pregnant women, with 572 (60%) receiving at least one dose of Pfizer, 321 (34%) Moderna, and 53 (6%) J&J, and 1,178 non-pregnant women. Demographic and medical history were similar across manufacturers for both cohorts.Overall, pregnant women reported similar side effects as non-pregnant women, with the most common being injection site reactions (83 vs. 87%), fatigue (72 vs.78%), and headache (45 vs. 59%). Pregnant women reported fewer side effects (median: 3 vs. 4, respectively) (Table 2). In both cohorts, very few reported seeking medical care (<5%) or being hospitalized (<0.3%) after vaccination. Fewer pregnant women reported working less after vaccination than non-pregnant women (32 vs. 40%) or trouble with self-care (32 vs. 46%), respectively (Table 2). Conclusion Pregnant women reported similar COVID-19 vaccine side effects as non-pregnant women, although fewer total side effects; pregnant women judged these side effects to have less impact on work and self-care. While these results do not address pregnancy outcomes or long-term effects, findings about acute side effects and impact offer reassurance for all three vaccines in terms of tolerability. Key Points

Introduction: The emergency department (ED) evaluation of suspected acute coronary syndrome (ACS) is a common, challenging, and costly task with high clinical stakes. Professional society guidelines recommend early stress testing (within 72 hours of ED visit); however, there are no data to demonstrate improved outcomes with this approach. Hypotheses: 1.) Early stress testing improves outcomes, and 2.) The association between early stress testing and outcomes is modified by pre-test ACS risk. Methods: We analyzed prospectively collected registry data from 9 emergency departments on patients with suspected ACS. The primary outcome was 30-day major adverse cardiovascular events (MACE), including all-cause death, acute myocardial infarction, and urgent revascularization. The exposure variable of interest was early stress testing. We used the HEART score to determine pre-test ACS risk (low, intermediate, high). To mitigate potential confounding by indication, patients with and without early stress testing were matched in a 1:2 ratio using propensity score methods. The propensity score model included over 40 demographic, clinical, biomarker, and ECG covariates. Results: The analytic cohort included 946 patients with early stress testing and 1,892 without early stress testing. There were no significant baseline imbalances after propensity score matching (p>0.1 for all covariates). There was no association between early stress testing and 30-day MACE in the overall cohort (OR 1.3; 95%CI 0.8-2.1). There was evidence of effect modification by pre-test ACS risk strata (low: OR 1.2, 95%CI 0.2-5.3; intermediate: 2.1, 95%CI 1.1-4.1; high: 0.4, 95%CI 0.1-1.4). In intermediate risk patients, early stress testing is associated with increased rates of revascularization (OR 2.8, 95%CI 1.3-6.0), but not with death/ acute myocardial infarction (OR 0.9, 95%CI 0.1-4.6). Conclusions: Early stress testing does not reduce 30-day MACE in the ED evaluation of suspected ACS. In intermediate-risk patients, early stress testing may result in increased revascularization rates without reduction in the objective outcomes of death or myocardial infarction. These findings challenge existing care guidelines and require confirmation by randomized trials.

Introduction: The hemodynamic gain index (HGI) is a novel simple parameter calculated from resting and peak systolic BP (SBP) and heart rate (HR) during exercise testing. It is a predictor of mortality in population-based cohorts. However, the prognostic significance of the HGI in chronic HFrEF has not been well studied. Hypothesis: The HGI is independently associated with adverse outcomes, and is comparable to other cardiopulmonary exercise testing (CPET) parameters. Methods: Medical records of 1,067 consecutive HFrEF patients (EF ≤ 40%) undergoing CPET for symptom evaluation from 12/2012 to 9/2020 were reviewed. HGI was calculated using the formula, [(SBP peak x HR peak )-(SBP rest x HR rest )]/(SBP rest x HR rest ). Patients with missing vital signs, hypotensive or bradycardic response to exercise were excluded. Primary outcome was the composite endpoint of all-cause mortality, LVAD implantation, and heart transplantation. Multivariable Cox proportional hazard models were used with subgroup analyses based on median age, sex, BMI of 35 kg/m 2 , respiratory exchange ratio (RER) of 1.05, and beta-blocker use. ROC curves with AUCs were used to compare HGI, peak VO 2 , VE/VCO 2 slope and peak end-tidal pressure of CO 2 (PEtCO 2 ). Results: We included 954 HFrEF patients (mean age was 56.3 ± 12.0 years, 72% men, 17% with BMI ≥ 35 kg/m 2 , 86% on beta-blockers, and 73% with RER > 1.05). During a median follow up time of 946 days, the incidence of the composite outcome was 331 (34.7%). After adjustment for age, sex, BMI, comorbidities, and EF, higher HGI was independently associated with lower risk of the adverse outcomes in the main cohort (hazard ratio per unit increase 0.46, 95%CI 0.35 to 0.59, p < 0.001), and all subgroups, except for patients with BMI ≥ 35 kg/m 2 ( Figure 1A ). The HGI was also comparable to peak VO 2 , and outperformed VE/VCO 2 slope and PEtCO 2 ( Figure 1B ). Conclusions: The HGI is an independent predictor of adverse outcomes, and comparable to peak VO 2 in patients with chronic HFrEF.

Abstract Background The aim of this paper was to provide an initial validation of a newly developed parent questionnaire—the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders. Methods The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; Mage = 7.19 years, SDage = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; Mage = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2). Results Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of ≥ .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group. Conclusions Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD.

BackgroundThe present study aims to investigate one of the major causes of traffic accidents: drivers' unsafe behaviors while driving.MethodsIn this cross-sectional study, the behaviors of 946 drivers at traffic lights were observed in the morning, at noon, and in the evening using direct in-field observation. The unsafe behaviors of the drivers included not fastening the seat belt, using a cellphone or handsfree device, smoking, being distracted by a child, talking with passengers, not observing the stop line, eating and drinking, and getting out of the car, letting out a passenger, or arguing with a passenger at the traffic light.ResultsOf the drivers at the traffic light, 60% did not obey the stop line, and 72% did not fasten their seat belt. Also, 13.6% used their cellphones, and 22% talked with passengers. The frequency of the other unsafe behaviors was &lt;3%. For wearing seat belts, drivers aged 41–50 years wore seat belts almost five times more than drivers under 25 years of age (4.94 [2.36–10.320]; p &lt; 0.001), and drivers aged 50 years and older were almost three times likelier to wear seat belts than drivers under 25 years of age (2.8 [1.31–6.08]; p &lt; 0.001). The results showed that the drivers were significantly likelier to wear seat belts on Saturdays (after the weekend) (0.56 [0.40–0.78]; p = 0.001). Regarding using mobile phones while driving, women were twice as likely to use mobile phones as men (2.20 [1.30–3.72]; p &lt; 0.001). Drivers aged 26–40 years used mobile phones significantly less than drivers under 25 years of age (0.24 [0.14–0.43]; p &lt; 0.001) and drivers aged 41–50 years were significantly less likely to use mobile phones than drivers under 25 years of age (0.19 [1.31–6.08]; p &lt; 0.001).ConclusionThe results showed that the occurrence of wearing a seat belt in Shahin Dej was low. We observed a significant association between wearing a seat belt, age, whether it was Saturday (a day after weekend for Iranians). Additionally, similar associations were observed between using mobile phones and gender, age, and day of the week.

BackgroundT1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat‐water separation with T1‐weighting to enable imaging of water‐specific T1 (T1Water), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown.PurposeDetermine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*‐compensation approach to reduce T1 variability.Study TypeProspective observational; phantoms.PopulationsOne hundred twenty‐four controls (56 male, 18–75 years), 50 patients at‐risk for liver disease (18 male, 30–76 years).Field Strength/Sequence2.89 T; Saturation‐recovery chemical‐shift encoded T1 Mapping (SR‐CSE); MOLLI.AssessmentSR‐CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*‐compensation approach to reduce T1 variability was evaluated test/re‐test reproducibility.Statistical TestsLinear regression, ANCOVA, t‐test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant.ResultsLiver T1 values were significantly higher in healthy females (F) than males (M) for both SR‐CSE (F‐973 ± 78 msec, M‐930 ± 72 msec) and MOLLI (F‐802 ± 55 msec, M‐759 ± 69 msec). T1 values were negatively correlated with age, with similar sex‐ and age‐dependencies observed in T2*. The T2*‐compensation model reduced the variability of T1 values by half and removed sex‐ and age‐differences (SR‐CSE: F‐946 ± 36 msec, M‐941 ± 43 msec; MOLLI: F‐775 ± 35 msec, M‐770 ± 35 msec). At‐risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*‐compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1‐bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters.Data ConclusionLiver T1Water values were lower in males and decreased with age, as observed for SR‐CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat‐modulated T1 bias. T2*‐compensation removed sex‐ and age‐dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at‐risk groups.Evidence Level2Technical EfficacyStage 1

Avaliou-se a capacidade de conversão de isoflavonas glicosiladas às suas formas agliconas pelo uso de β- glicosidase de Aspergillus oryzae ATCC 22786. A produção de daidzeína e genisteína foi acompanhada por 96 h de fermentação em estado sólido, usando-se farelo de soja e suspensão de esporos do fungo a 30ºC. Notou-se a conversão de glicosil-isoflavonas após 24 h e redução significativa na sua quantidade, depois de 48 h de fermentação. A atividade enzimática acompanhou a formação de produto até 72 h (0,2 UI/ mL), apresentando leve diminuição em 96 h (0,19 UI/ mL). Após 48 h obteve-se conversão total de daidzina e genistina, com formação de 551,1 e 17,2 µg/g de daidzeína e genisteína, respectivamente. A produção de genisteína, no entanto, mostrou-se significativamente superior em 24 h de fermentação (289,3 µg/g). Concluiuse que a β-glicosidase produzida por Aspergillus oryzae ATCC 22786 foi capaz de converter glicosilisoflavonas em agliconas por fermentação em estado sólido a 30ºC. CONVERSION OF SOY DAIDZEIN AND GENISTEIN BY β -GLUCOSIDASE OF Aspergillus oryzae Abstract The conversion capacity of glucoside isoflavones to aglycones by Aspergillus oryzae ATCC 2786 β-glucosidase was evaluated. The production of daidzein and genistein was observed for 96 h in solid state fermentation, by utilizing soy flour and a suspension of fungal spores at 30ºC. The conversion of glucoside isoflavones was noted after 24 h and a significant reduction in its quantity after 48 h of fermentation. The enzymatic activity followed the product formation until 72 h (0.2 UI/mL), showing a slight reduction in 96 h (0.19 UI/mL). After 48 h total conversion of daidzein and genistein was obtained, with formation of 551.1 and 17.2 µg/g of daidzein and genistein, respectively. The production of genistein, however, was significantly higher in 24 h of fermentation (289.3 µg/g). It was concluded that the produced β-glucosidase by Aspergillus oryzae was capable to convert glucoside isoflavones in to aglycones by solid state fermentation at 30ºC.

Background: Depression contributes to the suboptimal health outcomes among people with type 1 diabetes (T1D) . American Diabetes Association recommends depression screening in individuals with T1D. We aim to demonstrate the use of QI tools in expanding depression screening in the T1D Exchange Learning Collaborative (T1DX-LC) Method: Six clinics in the T1DX-LC participated in expanding depression screening utilizing PHQ-2, PHQ-4, or PHQ-9. The clinics applied QI principles to design plan-do-study-act cycles to develop, improve, and adapt interventions. The interventions tested include use of a screener at visits, expanding screening to age 12, pulling weekly data to flag patients that should be screened, peer support group, standardizing screening workflow, use of EHR/health information technology, provider training, monthly meetings to discuss screening protocol, and streamlining referral process. The hospitals shared monthly aggregate data with the T1DX-LC Result: Participating clinics were successful at implementing depression screening. Screening increased from a baseline of 59% to 72% over 17 months Conclusion: Utilizing the PHQs for depression screening is feasible and QI principles are useful in expanding screening rates. Continued expansion of depression screening is necessary to improve emotional well-being and diabetes self-care management Disclosure O.Odugbesan: n/a. A.Mungmode: None. N.Rioles: None. D.Brimberry: None. G.Nelson: None. A.J.Feuer: None. J.Ilkowitz: None. S.A.Dei-tutu: None. O.Ebekozien: None. Funding The QI learning collaborative is supported by Helmsley Charitable Trust

Aims: Previous studies proved that glucose coefficient of variation (CV), an index of glycemic variability (GV), affected the relationship between TIR and glucose management indicator (GMI) in patients with diabetes. This study aimed to explore whether other GV indexes, including MAGE and SD of glucose, affect the relationship between TIR and GMI in T2D patients. Methods: Data were collected from T2D patients who received 48-h to 72-h CGM with iPro2 between January 2018 and October 2019. GV indexes, TIR, and GMI were derived from iPro2. A linear regression equation was generated with values of TIR and GMI. Patients were then divided into 3 subgroups according to the values of MAGE or SD. Predicted TIR in given GMI was calculated via the linear regression equations in the respective tertiles groups of MAGE or SD. Results: A total of 118 T2D patients who were 57.2±11.6 years old, with a median diabetes duration of 6.0 years, HbA1c of 6.9±1.2%, and TIR of 87.5±12.9% were included. There was a strong negative correlation between TIR and GMI (r=-0.762, P&lt;0.001). The linear regression equation was TIR%=-21.2× GMI%+224.6. Multiple linear regression analysis showed that both MAGE and SD have impacts on the relationship between TIR and GMI (P&lt;0.001). The predicted TIR decreased when MAGE or SD increased with different given GMI (Table 1). Conclusions: MAGE and SD influenced the relationship between TIR and GMI in T2D patients. Disclosure D.Chen: None. Z.Liu: None. B.Lin: None. D.Yang: None. J.Yan: None. Y.Yang: None. W.Xu: None.

Abstract Introduction Older adults who sustain a hip fracture require complex multidisciplinary care, which can challenge organisational structures within hospitals. Despite standards and guidelines, substantial variation remains in hip fracture care delivery across the UK. We aimed to determine which hospital-level organisational factors predict adverse patient outcomes in the post injury period. Method A cohort of 178,757 patients aged 60+ years in England and Wales (2016–19) who sustained a hip fracture was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality data were linked to metrics from 18 hospital-level organisational audits/reports/series. Multilevel models determined the organisational factors, independent of patient case-mix, associated with three patient outcomes: length of hospital stay (LOS), 30-day all-cause mortality, and emergency 30-day readmission. Results Overall LOS was mean 21 days (standard deviation, 20); 13,126 (7.3%) died within 30-days; and 25,239 (15.3%) were readmitted. 25 organisational factors independently predicted LOS: for example, a hospital’s ability to promptly mobilise ≥90% of patients was associated with a 2-day (95%CI:1.3–2.7) shorter LOS, and hospitals where all patients received orthogeriatric assessment within 72 hours of admission had mean 1.5-day (95%CI:0.6–2.3) shorter LOS. Ten organisational factors independently predicted 30-day mortality: providing prompt surgery (≤36 hours from admission) to &gt;80% patients was associated with the same 10% reduction in mortality (95%CI:4–15%), as was discussion of ‘patient experience’ feedback at clinical governance meetings (95%CI:5–15%). Nine organisational factors independently predicted readmission: knowledge of time from discharge to start of community therapy was associated with 17% (95%CI:9–24%) lower readmission rates. Organisational delivery of clinical governance, surgery, and physiotherapy were associated with all outcomes. Conclusion Multiple, potentially modifiable, organisational factors are associated with important patient outcomes post-hip fracture. These factors, if causal, indicate auditable components of hospital care where interventions can be targeted to reduce variability in hip fracture care delivery, to improve patient outcomes.

RNA drugs are a new group of drugs that delivers RNAs or similar structures inside the body to achieve the therapeutic effect. This is a promising direction in drug development to treat serious and rare genetic diseases more specifically and effectively. In reality, the genetic systems and protein synthesis processes of living organisms are extremely complex, so the development of RNA drugs faces many difficulties. To achieve success, many different studies have been carried out to address issues such as finding suitable RNAs, synthesizing similar RNA structures, stabilizing RNA structures, and introducing drugs into targeted cells. Since the first RNA drug was officially approved by the FDA (2004), 10 RNA drugs in total have been approved to date. Among them, two vaccines, appearing at the time when much needed support to cope with the new SARS-CoV-2 variants, were developed using mRNA technology. With these achievements, scientists can have more confidence in the possibilities of evolving a new drug group that is more specific and effective, which is RNA drugs. This review briefly introduces the group of drugs that use RNAs, RNA structural analogs, and RNA biomarkers to develop novel drugs for application in the diagnosis, prevention, and treatment of disease. Keywords: RNA drugs; mRNA; the protein; vaccines; RNA diagnostics; small molecule drugs; RNA target. References [1] U. Sahin, K. Karikó, Ö. Türeci, Mrna-Based Therapeutics-Developing A New Class of Drugs, Nature Reviews Drug Discovery, Vol. 13, No. 10, 2014, pp. 759-780.[2] T. H. Nguyen, T. M. H. Pham, M. K. Tu, Pharmacogenetics: Prospects and Issues. Journal of Pharmacy, No. 54, Vol. 456, 2014, pp. 2-6.[3] A. M. Yu, Y. H. Choi, M. J. Tu, Rna Drugs and Rna Targets for Small Molecules: Principles, Progress, and Challenges, Pharmacological Reviews, Vol. 72, No. 4, 2020, pp. 862-898.[4] M. A. Hendaus, F. A. Jomha, Mrna Vaccines for Covid-19: A Simple Explanation, Qatar Medical Journal, Vol. 2021, No. 1, 2021, pp. 1-5.[5] A. Banerji, P. G. Wickner, R. Saff, C. A. Stone Jr, L. B. Robinson, A. A. Long et al., Mrna Vaccines to Prevent Covid-19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach, the Journal of Allergy and Clinical Immunology: in Practice, Vol. 9, No. 4, 2021, pp. 1423-1437.[6] https://www.Fda.Gov/Emergency-Preparedness-and-Response/Coronavirus-Disease-2019-Covid-19/Covid-19-Vaccines (accessed on: December 15th, 2021).[7] E. H. Aarntzen, G. Schreibelt, K. Bol, W. J. Lesterhuis, A. J. Croockewit, J .H. De Wilt et al., Vaccination with Mrna-Electroporated Dendritic Cells Induces Robust Tumor Antigen-Specific Cd4+ and Cd8+ T Cells Responses in Stage Iii and Iv Melanoma Patients, Clinical Cancer Research, Vol. 18, No. 19, 2012, pp. 5460-5470.[8] H. M. Phan, K. L. Vu, T. H. Nguyen, T. T. Bui, A Comprehensive Review of Vaccines Against Covid-19, VNU Journal of Science: Medical and Pharmaceutical Sciences, Vol. 37, No. 3, 2021, pp. 1-19 (in Vietnamese).[9] N. Pardi, M. J. Hogan, F. W. Porter, D. Weissman, Mrna Vaccines - A New Era in Vaccinology, Nature Reviews Drug Discovery, Vol. 17, No. 4, 2018, pp. 261-279.[10] G. Wen, T. Zhou, W. Gu, The Potential of Using Blood Circular Rna As Liquid Biopsy Biomarker for Human Diseases. Protein & Cell, Vol. 12, No. 12, 2021, pp. 911-946.[11] S. Sabarimurugan, C. Kumarasamy, S. Baxi, A. Devi, R. Jayaraj, Systematic Review and Meta-Analysis of Prognostic Microrna Biomarkers for Survival Outcome in Nasopharyngeal Carcinoma. Plos One, Vol. 14, No. 2, 2019, pp. 1-18.[12] F. Wang, T. Zuroske, J. K. Watts, Rna Therapeutics on the Rise, Nat Rev Drug Discov, Vol. 19, No. 7, 2020, pp. 441-442.[13] E. J. Wild, S. J. Tabrizi, Therapies Targeting Dna and Rna in Huntington's Disease, The Lancet Neurology, Vol. 16, No. 10, 2017, pp. 837-847.[14] H. Han, Rna Interference to Knock Down Gene Expression, Disease Gene Identification, 2018, pp. 293-302.[15] J. Kim, C. Hu, C. M. E. Achkar, L.E. Black, J. Douville, A. Larson et al., Patient-Customized Oligonucleotide Therapy for A Rare Genetic Disease, New England Journal of Medicine, Vol. 381, No. 17, 2019, pp. 1644-1652.[16] U. Food, D. Administration, Fda Approves First-of-Its Kind Targeted Rna-Based Therapy to Treat A Rare Disease, Silver Spring (Md): Usfda, 2018.[17] E. Sardh, P. Harper, M. Balwani, P. Stein, D. Rees, D. M. Bissel et al., Phase 1 Trial of An Rna Interference Therapy for Acute Intermittent Porphyria, New England Journal of Medicine, Vol. 380, No. 6, 2019, pp. 549-558.[18] G. Devi, Sirna-Based Approaches in Cancer Therapy, Cancer Gene Therapy, Vol. 13, No. 9, 2006, pp. 819-829.[19] T. G. Hopkins, M. Mura, H. A. A. Ashtal, R. M. Lahr, N. A. Latip, K. Sweeney et al., The Rna-Binding Protein Larp1 Is A Post-Transcriptional Regulator of Survival and Tumorigenesis in Ovarian Cancer, Nucleic Acids Research, Vol. 44, No. 3, 2016, pp. 1227-1246.[20] V. Iadevaia, M. D. Wouters, A. Kanitz, A. M. M. González, E. E. Laing, A. P. Gerber, Tandem Rna Isolation Reveals Functional Rearrangement of Rna-Binding Proteins on Cdkn1b/P27 Kip1 3’utrs in Cisplatin Treated Cells, Rna Biology, Vol. 17, No. 1, 2020, pp. 33-46.[21] T. T. Bui, K. S. Phan, T. M. H. Pham, T. H. Nguyen, PEGylation of Curcumin and Prospect of Application, VNU Journal of Science: Medical and Pharmaceutical Sciences, Vol. 32, No. 1, 2016, pp 1-11.

Who Are Carers? A carer is any individual who provides unpaid care and support to a family member or friend who has a disability, mental illness, drug and/or alcohol dependency, chronic condition, terminal illness or who is frail. Carers come from all walks of life, cultural backgrounds and age groups. For many, caring is a 24 hour-a-day job with emotional, physical and financial impacts, with implications for their participation in employment, education and community activities. Carers exist in all communities, including amongst Aboriginal communities, those of culturally and linguistically diverse backgrounds, amongst Gay, Lesbian, Bisexual, Transgender, Intersex communities, and throughout metropolitan, regional and rural areas (Carers NSW). These broad characteristics mean that caring occurs across a wide variety of situations and care responsibilities can impact an even wider group of people. The ubiquitous nature of informal care warrants its consideration as a major social issue, as well as the potential impacts that these roles can have on carers in both short and long term contexts. Caring for a loved one is often an unseen component of people’s domestic lives. As will be outlined below, the potentially burdensome nature of care can have negative influences on carers’ wellbeing. As such, factors that can enhance the resilience of carers in the face of such adversity have been widely investigated. This being said, individual differences exist in carers’ responses to their caring responsibilities. The caring experience can therefore be argued to exist on a continuum, from the adversity in relation to stressful challenges through to prosperity in light of their caring responsibilities. By considering the experience of care as existing along this continuum, the place of resilience within people’s domestic spaces can be viewed as a mechanism towards identifying and developing supportive practices. Negative Impacts of Care A significant body of research has identified potential negative impacts of caring. Many of the most commonly cited outcomes relate to negative effects on mental health and/or psychological functioning, including stress, anxiety and depression (e.g. Baker et al.; Barlow, Cullen-Powell and Cheshire; Cheshire, Barlow and Powell; Dunn et al.; Gallagher et al.; Hastings et al.; Lach et al.; Singer; Sörensen et al.; Vitaliano, Zhang and Scanlan; Whittingham et al.; Yamada et al.). These feelings can be exacerbated when caring responsibilities become relentlessly time consuming, as demonstrated by this comment from a carer of a person with dementia: “I can’t get away from it” (O'Dwyer, Moyle and van Wyk 758). Similarly, emotional responses such as sorrow, grief, anger, frustration, and guilt can result from caring for a loved one (Heiman; Whittingham et al.). Negative emotional responses are not necessarily a direct result of caring responsibilities as such, but an understanding of the challenges faced by the person requiring their care. The following quote from the carer of a child with autism exemplifies the experience of sorrow: “It was actually the worst day of our lives, that was the day we came to terms with the fact that we had this problem” (Midence and O’Neill 280). Alongside these psychological and emotional outcomes, physical health may also be negatively impacted due to certain demands of the caring role (Lach et al.; Sörensen et al.; Vitaliano, Zhang and Scanlan). Outcomes such as these are likely to vary across individual caring circumstances, dictated by variables such as the specific tasks required of the carer, and individual personality characteristics of both the carer and the person for whom they care. Nevertheless, an awareness of these potential outcomes is particularly important when considering the place of resilience in the domestic space of individuals caring for a loved one. This conceptualisation of caring as being a burdensome task reflects many publicly held perceptions. If caring is widely viewed as compromising carers’ wellbeing, then there is likely to be an increased likelihood of carers viewing themselves as victims. This is particularly true amongst children and adolescents with caring responsibilities, since young people are most susceptible to having their personal identities shaped by others’ perceptions (Andreouli, Skovdal and Campbell). Resilience in Caring Adversity Despite the widely acknowledged potential for caring to have negative consequences for carers, it must be noted that the occurrence of these outcomes are not inevitable. In fact, much of the research that has identified increased stress amongst carers also finds that the majority cope well with the demands of their role (Barnett et al.). These carers have been considered by many researchers to demonstrate resilience (e.g. Barnett et al.; O'Dwyer, Moyle and van Wyk). The ability to respond positively despite exposure to risk or adversity is a key feature of most definitions of resilience (Luthar, Cicchetti and Becker; Masten and Obradović; Zauszniewski, Bekhet and Suresky). Resilience in this context can thus be defined as a psychological process that facilitates healthy functioning in response to intense life stressors (Johnson et al.). Since caring experiences are likely to continue for an extended period of time, resilience is likely to be necessary on an ongoing basis, rather than in response to a single traumatic event. A resilient carer is therefore one who is able to effectively and adaptively cope with extenuating pressures of caring for a loved one. This involves the presence of personal, social, familial, or institutional protective factors that enable carers to resist stress (Kaplan et al.). For example, support from health professionals, family, or community has been found to effectively support carers in coping with their role (Bekhet, Johnson and Zauszniewski; Gardiner and Iarocci; Heiman; Whittingham et al.). The benefit of support networks in assisting carers to cope in their role is widely reported in the associated research, reinforced by many examples such as the following from a carer of a person with dementia: “It’s a social thing, like, I’ve got friends on there… I find that is my escape” (O'Dwyer, Moyle and van Wyk 758). At an individual level, those who demonstrate resilient in the face of adversity demonstrate optimistic or hopeful outlooks (Ekas, Lickenbrock and Whitman; Lloyd and Hastings; Whittingham et al.), while simultaneously holding realistic expectations of the future (Rasmussen et al.; Wrosch, Miller, et al.; Wrosch, Scheier, et al.). Such attitudes are particularly significant amongst people caring for family members or friends with disabilities or illnesses. The following attitude held by a carer of a child with cerebral palsy exemplifies this optimistic outlook: “I look at the glass half full and say that “well, it’s only his walking, everything else is fine”. “So, get over [it] and deal with it” (Whittingham et al. 1451). Those who cognitively process information, rather than reacting in a highly emotion way have also been found to cope better (Bekhet, Johnson and Zauszniewski; Heiman; Monin et al.; Pennebaker, Mayne and Francis), as have those with a greater sense of self-efficacy or an internal locus of control (Bekhet, Johnson and Zauszniewski; Kuhn and Carter). However effective these coping strategies prove to be, this is unlikely to provide the full picture of caring experiences, or the place of resilience within that space. Associating resilience with adversity presumes a consensus on what constitutes adversity. Taking the typical approach to investigating resilience amongst carers risks making undue assumptions of the nature of individual carers’ experiences – namely, that caring equates to adversity. The following paragraphs will outline how this is not necessarily the case. And furthermore, that the concept of resilience still has a place in considering informal caring, regardless of whether adversity is considered to be present. Benefits of Care While a great deal of evidence suggests that caring for a loved one can be a stressful experience, research has also demonstrated the existence of positive impacts of care. In many instances, carers not only cope, but also thrive in their caring roles (Turnbull et al.). Elements such as positive relationships within caring relationships can both challenge and strengthen individuals – factors that only exist due to the specific nature of the individual caring role (Bayat; Heiman). Such positive elements of the caring experience have been reflected in the literature, illustrated by quotes such as: “In some sense, this makes our family closer” (Bayat 709). Rather than viewing carers from a perspective of victimisation (which is particularly prominent in relation to children and young people with caring responsibilities), recognising the prevalence of positive wellbeing within this population provides a more nuanced understanding of the lived experiences of all carers (Aldridge). Reported benefits of caring tend to revolve around personal relationships, particularly in reference to parents caring for their children with special needs. Reflective of the parental relationship, carers of children with disabilities or chronic illnesses generally report feelings of love, joy, optimism, strength, enjoyment, and satisfaction with their role (Barnett et al.; Heiman). The views of such carers do not reflect an attitude of coping with adversity, but rather a perspective that considers their children to be positive contributors to carers’ quality of life and the wellbeing of the wider family (King et al.). This point of view suggests an additional dimension to resilience; in particular, that resilience in the relative absence of risk factors, can cause carers to flourish within their caring role and relationships. In addition to benefits in relationships, carers may also prosper through their own personal growth and development in the course of their caring (Knight). This includes factors such as the development of life skills, maturity, purpose, social skills, a sense of responsibility, and recognition – particularly amongst young people in caring roles (Earley, Cushway and Cassidy; Early, Cushway and Cassidy; Jurkovic, Thirkield and Morrell; Skovdal and Andreouli; Stein, Rotheram-Borus and Lester; Tompkins). Recognition of the potential personal benefits of caring for a loved one is not intended to suggest that the view of carers coping with adversity is universally applicable. While it is likely that individual caring situations will have an impact on the extent to which a carer faces adversity (e.g. intensity of caring responsibilities, severity of loved one’s impairment, etc.), it is important to recognise the benefits that carers can experience alongside any challenges they may face. Circumstances that appear adversarial may not be thought of as such by those within that context. Defining resilience as an ability to cope with adversity therefore will not apply to such contexts. Rather, the concept of resilience needs to incorporate those who not only cope, but also prosper. Carers who do not perceive their role as burdensome, but identify positive outcomes, can therefore be said to demonstrate resilience though contextually different from those coping with adversity. This is not to suggest that resilience is the sole contributing factor in terms of prospering in the caring role. We must also consider individual circumstances and nuances differ between carers, those they care for, interpersonal relationships, and wider caring situations. Continuum of Care Awareness of the range of impacts that caring can have on carers leads to a recognition of the broad spectrum of experience that this role entails. Not only do caring experiences exhibit large variations in terms of practical issues (such as functional capacities, or type and severity of illness, disability, or condition), they include carers’ diverse personal responses to caring responsibilities. These responses can reflect either positive or negative dimensions, or a combination of both (Faso, Neal-Beevers and Carlson). In this way, caring experiences can be conceptualised as existing along a continuum. At one end of the spectrum, experiences align with the traditional view of caring as a struggle with and over adversity. More specifically, carers experience burdens as a result of their additional caring responsibilities, with negative outcomes likely to occur. At the other end of the spectrum, however, carers prosper in the role, experiencing significant personal benefits that would not have been possible without the caring role. This continuum makes a case for an expanded approach to stress and coping models of resilience to include positive concepts and a benefit-orientated perspective (Cassidy and Giles). In contrast to research that has argued for a progression from stress and coping models to strengths-based approaches (e.g. Glidden, Billings and Jobe; Knight), the continuum of care acknowledges the benefits of each of these theoretical positions, and thus may prove more comprehensive in attempting to understand the everyday lived experiences of carers. The framework provided by a representation of a continuum allows for the individual differences in caring situations and carers’ personal responses to be acknowledged, as well as accounting for any changes in these circumstances. Further, the experience and benefits of resilience in different contextual spheres can be identified. The flexibility afforded by such an approach is particularly important in light of individual differences in the ways carers respond to their situations, their changing caring contexts, and their subsequent individual needs (Monin et al.; Walsh; Whittingham et al.). As the caring experience can be dynamic and fluctuate in both directions along the continuum, resilience may be seen as the mechanism by which such movement occurs. In line with stress and coping models, resilience can assist carers to cope with adversarial circumstances at that end of the continuum. Similarly, it may be argued that those who prosper in their caring role exhibit characteristics of resilience. In other words, it is resilience that enables carers to cope with adversity at one end of the continuum and also to prosper at the other. Furthermore, by supporting the development of resilient characteristics, carers may be assisted in shifting their experiences along the continuum, from adversity to prosperity. This view extends upon traditional approaches reported in the stress and coping literature by contending that caring experiences may progress beyond positions of coping with adversity, to a position where caring is not understood in terms of adversity at all, but rather in terms of benefits. The individual circumstances of any carer must be taken into consideration with this framework of resilience and the continuum of care. It is unrealistic to assume that all caring situations will allow for the possibility of reaching the end point of this continuum. Carers with particularly high demands in terms of time, resources, effort, or energy may not reach a stage where they no longer consider their caring role to involve any personal burden. However, the combination of a coping and strengths-based approach suggests that there is always the possibility of moving away from perceptions of adversity and further towards an attitude of prosperity. Implications for Supportive Practice From the perspective of this continuum of care, the protective factors and coping strategies identified in previous literature provide a valuable starting point for the facilitation of resilience amongst carers. Enhancing factors such as these can assist carers to move from situations of adversity towards experiences of prosperity (Benzies and Mychasiuk). Research has suggested that carers who are less analytical in their thinking and less optimistic about their personal situations may find particular benefit from support systems that assist them in redirecting their attention towards positive aspects of their daily lives, such as the benefits of caring outlined earlier (Monin et al.). The principle of focusing on positive experiences and reframing negative thoughts is thought to benefit carers across all levels of functioning and adaptive experience (Monin et al.). While those entrenched in more burdensome mindsets are likely to experience the greatest benefit from supportive interventions, there is still merit in providing similar supports to carers who do not appear to experience the similar experiences of burden, or demonstrate greater resilience or adaptation to their situation. The dynamic view of caring situations and resilience suggested by a continuum of care incorporates benefits of stress and coping models as well as strengths-based approaches. This has implications for supportive practice in that the focus is not on determining whether or not a carer is resilient, but identifying the ways in which they already are resilient (Simon, Murphy and Smith). For carers who experience their role through a lens of adversity, resilience may need to be purposefully fostered in order to better enable them to cope and develop through the ongoing stresses of their role. For carers at the other end of the spectrum, resilience is likely to take on a substantially different meaning. Under these circumstances, caring for a loved one is not considered a burdensome task; rather, the positive impact of the role is pre-eminent. This point of view suggests that carers are resilient, not only in terms of an ability to thrive despite adversity, but in prospering to the extent that adversity is not considered to exist. The attitudes and approaches of services, support networks, and governments towards carers should remain flexible enough to acknowledge the wide variety of caring circumstances that exist. The continuum of care provides a framework through which certain aspects of caring and variations in resilience can be interpreted, as well as the type of support required by individual carers. Furthermore, it must be noted that caring circumstances can change – either gradually or suddenly – with the extent to which carers experience adversity, coping or prosperity also changing. Any attempts to provide support to carers or acknowledge their resilience should demonstrate an awareness of the potential for such fluctuation. 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