Journal articles on the topic 'In Utro (Firm)'

Fire has long served as a tool in agriculture, but the practice's link with economic activity has made its health consequences difficult to study. Drawing on data from satellite-based fire detection systems, air monitors, and vital records in Brazil, we study how in utero exposure to smoke from sugarcane harvest fires affects health at birth. Exploiting daily changes in fire location and wind direction for identification, we find that late-pregnancy smoke exposure decreases birthweight, gestational length, and in utero survival. Fires less associated with smoke exposure predict improved health, highlighting the importance of disentangling pollution from its economic correlates.

Pregnancy-related cancer management represents a real challenge for both the patients and the physicians. The long-term neurodevelopmental outcome of children in utero exposed to chemotherapeutic agents has only recently been addressed. This review aims to systematically integrate and highlight all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All eligible studies are based on validated neurodevelopmental testing scales (e.g., Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence) and/or well-defined questionnaires. Our systematic review including 17 studies demonstrates that no major consequences on the neurodevelopment of children after in utero exposure to anti-cancer drugs have been reported; nevertheless, longer and more thorough follow-up with large-scale multicenter prospective studies is certainly required in order to draw firm conclusions.

With ongoing globalization, many business opportunities emerge all over the world. Operating business in one single country means to fail at exploiting additional profit from exporting one’s product or service globally. The following report will analyst the business operations of the company Utero, a creative design agency, responsible for brand, design and consultant services and located in Indonesia. As the company is already very successful in their country of origin, they should start exporting their services to other countries, to grow and yield additional profit. In order to do so, we will construct a marketing plan for Utero, based on a thorough analysis of the company’s background, its vision, mission and organizational structure. Also, we are going to assess the readiness of the company to do international marketing. Finally, we are going to give advice on how to successfully develop and implement international marketing, to enter markets all over the world. We found, that Utero should implement different marketing strategies, such as publishing a video of the firm online to increase brand awareness and spread it on social media networks such as Facebook. Other possible ideas would be to create a company-based Facebook page or create advertisement that will be displayed on YouTube. In general, our report aims at leading the company Utero on a successful path for further development and we believe that our proposed marketing plan will enable the company to significantly expand their business.

Background: Chronic, low-intensity air pollution exposure has been consistently associated with increased atherosclerosis in adults. However, there was limited research regarding the implications of acute, high-intensity air pollution exposure during childhood. We aimed to determine whether there were any associations between early-life exposure to such an episode and early-life vascular function changes. Methods: We conducted a prospective cohort study of children (<9 years old) who lived in the vicinity of the Hazelwood coal mine fire (n = 206). Vascular function was measured using noninvasive diagnostic methods including carotid intima-media thickness and pulse wave velocity (PWV). Exposure estimates were calculated from prognostic models and location diaries during the exposure period completed by each participant’s parent. Linear mixed-effects models were used to determine whether there were any associations between exposure and changes in vascular outcomes at the 3- and 7-year follow-ups and over time. Results: At the 7-year follow-up, each 10 μg/m3 increase in daily PM2.5 in utero was associated with increased PWV (β = 0.13 m/s; 95% confidence interval [CI] = 0.02, 0.24; P = 0.02). The association between in utero exposure to daily PM2.5 was not altered by adjustment for covariates, body mass index, and maternal fire stress. Each 1 µg/m3 increase in background PM2.5 was associated with increased PWV (β = 0.68 m/s; 95% CI = 0.10, 1.26; P = 0.025), in children from the in utero exposure group. There was a trend toward smaller PWV (β = −0.17 m/s; 95% CI = −0.366, 0.02) from the 3- to 7-year follow-up clinic suggesting that the deficits observed previously in children exposed postnatally did not persist. Conclusion: There was a moderate improvement in vascular stiffness of children exposed to PM2.5 from a local coal mine fire in infancy. There was a mild increase in vascular stiffness in children exposed to PM2.5 from a local coal mine fire while their mothers were pregnant.

Urine samples were collected and pooled from four menopausal women , 47-55. years old, for extraction of gonadotropines ( LH & FsH) according to the method of Albert ( 1955 ) For evaluation the hormonal extract from menopausal women the following parameter were studied: a- Effect of crude hormonal extract on utero-ovarian weights of immature mice. b- Counting number of embryos & alive births in mice treated with crude extract. There was a significant effect of hormone extracted fiom menopausal women on utero-ovaian weights for immature mice. The crude extract caused a significant increase in number of embryos and alive Lebirths compared with saline-treated mice , it is concluded that crude extract from urine of menopausal women have highly biological activity for increase fertility in female mice.

Vascular adhesion protein-1 (VAP-1) is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surface-expressed oxidases. In adults, endothelial VAP-1 supports leukocyte rolling, firm adhesion, and transmigration in both enzyme activity-dependent and enzyme activity-independent manner. Here we studied the induction and function of VAP-1 during human ontogeny. We show that VAP-1 is already found in the smooth muscle at embryonic week 7. There are marked time-dependent switches in VAP-1 expression in the sinusoids of the liver, in the peritubular capillaries of the kidney, in the capillaries of the heart, and in the venules in the lamina propria of the gut. Fetal VAP-1 is dimerized, and it is enzymatically active. VAP-1 in fetal-type venules is able to bind cord blood lymphocytes. Also, adenovirally transfected VAP-1 on human umbilical vein endothelial cells is involved in rolling and firm adhesion of cord blood lymphocytes under conditions of physiologic shear stress. We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny.

ObjectiveTo evaluate whether vascular health in young children was associated with exposure to a 6-week episode of coal mine fire smoke or environmental tobacco smoke (ETS) in a retrospective cohort study.MethodsThree years after a coal mine fire in Victoria, Australia, we investigated the vascular health of children either in utero (n=75) or aged <2 years (postnatal exposure, n=96) at the time of the fire. The outcomes were the carotid intima-media thickness (IMT) and pulse wave velocity (PWV). The mean and peak daily particulate matter <2.5 µm in diameter (PM2.5) exposures were estimated based on their daily locations throughout the fire period. Multivariable linear regression models were used to test for associations between the fire-related PM2.5 and outcomes adjusted for relevant covariates including ETS.ResultsIn the postnatal-exposure group, each 10 µg/m³ increase in mean PM2.5 level was independently positively associated with PWV (β=0.116, p=0.028). When these two groups were combined, there was an association between mean PM2.5 and increased PWV in those children who had ETS exposure (β=0.148, p=0.033) or whose mothers smoked (β=0.151, p=0.011), but not in those not exposed to ETS or maternal smoking.ConclusionsThree years after a coal mine fire, infants aged up to 2 years at the time of exposure have increases in vascular stiffness. Although no adverse effects were observed in the in uterus exposure group, further follow-up study is needed to elucidate the long-term effects of coal mine fire smoke exposure.

In 2013, the drinking water for one-third of the households in Ronneby, Sweden, was found to be contaminated by perfluorinated alkyl substances (PFAS, >10,000 ng/L) from Aqueous Film Forming Foam (AFFF). In utero PFAS exposure can influence birth weight, but little is known about the effects at very high levels. This study aimed to examine the association between in utero PFAS exposure and birth weight. Infants with mothers from Ronneby exposed to contaminated water at home (high exposure) and infants with mothers from Ronneby not exposed to contaminated water at home (low exposure) were compared to infants with mothers from Blekinge county excluding Ronneby (referents). All infants born in Blekinge county 1995–2013 were included (n = 30,360). Differences in birth weight were only seen among infants born after 2005. For boys, Ronneby high exposure had a lower mean birth weight than referents (−54 g, 95% CI −97; −11). For girls, Ronneby high exposure had a higher mean birth weight than referents (47 g, 95% CI 4; 90). There were no differences in birth weight between referents and Ronneby low exposure. In conclusion, high exposure to PFAS may influence birth weight in a sex-specific way, although the effect estimates were relatively small.

When leukemia develops while baby is still in utero, it is known as Congenital leu-kemia (CL). CL is an extremely rare form of acute leukemia. CL are mostly Myeloid in origin in contrast to the pediatric leukemias that are usually of Lymphoid type. Congenital leukemias have a poor prognosis as compared to transient abnormal myelopoiesis that usually affect 10% of newborns associated with down syndrome and may also go into spontaneous remission. CL poses a diagnostic dilemma as clin-ical features are quite similar to sepsis.This case report also highlights the im-portance of reviewing peripheral blood films of all newborns that can easily differ-entiate between reactive white blood cells ad abnormal cell like blast cells. Keywords: Congenital acute myeloid leukemia, congenital leukemia, peripheral blood film..

Predictions of turbine blade film cooling have traditionally employed Reynolds-averaged Navier-Stokes solvers and two-equation models for turbulence. Evaluation of several versions of such models have revealed that the existing two-equation models fail to resolve the anisotropy and the dynamics of the highly complex flow field created by the jet-crossflow interaction. A more accurate prediction of the flow field can be obtained from large eddy simulations (LES) where the dynamics of the larger scales in the flow are directly resolved. In the present paper, such an approach has been used, and results are presented for a row of inclined cylindrical holes at blowing ratios of 0.5 and 1 and Reynolds numbers of 11,100 and 22,200, respectively, based on the jet velocity and hole diameter. Comparison of the time-averaged LES predictions with the flow measurements of Lavrich and Chiappetta (UTRC Report No. 90-04) shows that LES is able to predict the flow field with reasonable accuracy. The unsteady three-dimensional flow field is shown to be dominated by packets of hairpin-shaped vortices. The dynamics of the hairpin vortices in the wake region of the injected jet and their influence on the unsteady wall heat transfer are presented. Generation of “hot spots” and their migration on the film-cooled surface are associated with the entrainment induced by the hairpin structures. Several geometric properties of a “mixing interface” around hairpin coherent structures are presented to illustrate and quantify their impact on the entrainment rates and mixing processes in the wake region.

Purpose – The purpose of this paper is to investigate contingency factors on the emergence of university spin-off firms. The institutional and organisational factors the paper explores comprise the transfer potential of the university, the strategy and characteristics of the University Technology Transfer Organisations and specific support for spin-off formation. Design/methodology/approach – Based on a unique data set, this cross-sectional study analyses the population of 54 higher education institutions in Germany. At this, 31.4 per cent of the German universities with technology transfer activities participated in this study. Findings – The research identifies a high degree of heterogeneity in the qualification of University Technology Transfer Offices (UTTO) staff and the existence of an entrepreneurship support programme as important antecedents of spin-off formation. In addition, the results reveal that pursuing different or multiple transfer strategies will not be detrimental to the establishment of spin-offs. Practical implications – It seems that there is still a lack of consensus with respect to the importance of spin-offs as an effective channel to transform research results into economic value. Furthermore, universities aiming at the promotion of spin-offs need appropriate regulations which do not jeopardise the usage of research outcomes for entrepreneurial purposes. Originality/value – This study contributes to enhance the knowledge on what promotes and inhibits the formation of university spin-off firms, as it first analyses a considerable population of UTTOs in Germany and explicitly considers underexplored and new contingency factors.

Background: The cervix has to play dual role in human reproduction. During pregnancy, it should remain firm and closed allowing the fetus to grow in utero until functional maturity is attained while during labour it should soften and dilate, allowing the fetus to pass through the birth canal. Objective of present study was to know and compare the effect of oral Mifepristone with intracervical dinoprostone gel for cervical priming prior to induction of labour at term in an unfavorable cervix of primigravida.Methods: This was prospective randomized comparative study. 100 primigravid patients were included, 50 were placed in each group A and B. Tablet Mifepristone 200mg orally was given in group A patients and intracervical dinoprostone gel induction was done in group B patients. Pre induction Bishop’s score was noted at beginning to compare improvement in Bishop’s score after induction. Mode of delivery and induction to delivery interval in both the groups were studied.Results: After induction with Mifepristone 76% women had successful cervical ripening as compared to 56% with dinoprostone. Rate of vaginal delivery was 70% with Mifepristone and 58% with dinoprostone. There was no significant difference in induction to delivery interval between the groups. Ten percent and 2% belonging to mifepristone and dinoprostone group respectively, required NICU admissions.Conclusions: Mifepristone is more effective than dinoprostone for preinduction cervical ripening as it has high success rate of achieving cervical ripening, however there is no significant difference in the vaginal delivery rate and other maternal and fetal outcome.

Jagdish Chandra Basu proved through his experiments that all the plants and trees are alive and have feelings just like a human being has. He proved that plants react, laugh and also feel sad. This was proved in late ninetees. But Jain Agamas have been the source of this information for last 2500 years.carang utra speas a lot aout anaspati ayi eeva (souls living in te bodies of plants and trees) and their feelings.The details are so live that one gets emotional for these so called non living things.Not only vanaspati (plants) but prithvi (earth), Apkaay (water), tejas (fire) Vayu (air) are also alive as per Jain Canons. Unfortunately modern generations do not believe these facts until and unless they are proved by some scientific approach. Hence plants are considered to be alive after agdis andra asus eperiments , while other four types of Kayik Jeevas are considered to be non living things till now. No one believed the stories of Pushpaka Vimana in te pic Ramayana as people flying in air was not a scene that men of that era could imagine,but today we can see a large number of aeroplanes taking a lot of humans from one place to the other by air. Though inclination of scientists towards Indian Hindu literature is appreciable who are exploring ancient scriptures of Hindus for old technologies and ancient theories with new searches and researches based on the information provided in ancient literature, but Jain literature has not been explored well till now while they have case studies of modern sciences like dream interpretation, medical sciences, colour therapies etc. This study attempts to explore an ancient Jain book arivans urana for case studies of air travel. The authors have listed and interpreted case studies from the book which give us a glimpse of flying technologies used in that era, users of the technolgy Further scope of this study can be to prove all the technological evidences in modern theories and references. Modern interpretation of these theories may bring out the truth that ancient Indian stories are not just myths, they have strong technological roots and evidences in their ancient literature Further Scope of Study can be to analyse the case studies in Harivansh Purana for other sciences and technologies also.The authors have focused on flying technology in Harivansh Purana but the fact is that the book is dotted with case studies of many other sciences and technologies like dream interpretation, medical science, architectural sciences, numerology etc. too. A list of armours used in the battles can also be listed. A list of sciences and technologies available in that era has also been given in the book like Pragyapti and maya etc. Experts of various fields should come forward to explore Jaina treasure of sciences for the modern world--------------------------------------------------------------------------------------------------------------------*Lecturer cum Placement Officer, Subodh Institute of Management & Career Studies, Jaipur **Lead Engineer, Samsung Research Institute, Bangalore

Abstract Background Beta thalassaemia is a genetic blood disease that causes life-threatening anemia. Hematopoietic stem cell (HSC) transplantation successfully cures the disease but in only 30% of patients. We hypothesized that in utero gene therapy (IUGT) to the fetal HSC compartment with the corrected beta globin gene might cure the disease before birth. Methods A humanized mouse model of thalassemia (Cooley's anemia; CA) was used in which heterozygous animals are affected by anemia, splenomegaly and extra-medullary hematopoiesis. At E13.5 a “GLOBE” vector (HIV-2 based lentiviral vector that incorporates a mini hemoglobin beta gene, the beta-globin promoter and HS2/3 β-LCR element) was injected into the liver of each fetus (n=12). At 12 weeks of age, recipient blood, liver, spleen and bone marrow were collected for complete blood count, blood film, as well as RNA and DNA isolation. Extra-medullary hematopoiesis was examined in the spleen and liver using flow cytometry (CD71+/Ter119+ cells) and histo-pathological analysis. Gene expression of human and mouse alpha and beta globins, as well as human gamma globin was assessed by quantitative polymerase chain reaction (qPCR). High performance liquid chromatography (HPLC) was used to quantify the presence of human beta globin in the peripheral blood of treated animals. Results are expressed as mean±SEM, and statistical analysis was performed using 1-way ANOVA with Bonferroni post-hoc tests. Experimental protocols were approved by the ethical committee on animal experimentation at University College London. Results Compared to non-injected heterozygous pups (control), IUGT increased hemoglobin levels [11.3±0.4g/dl (n=6) vs. 7.6±0.6g/dl (n=8); p<0.01], red blood cell count [9.3±0.3*1012/L vs. 6.2±0.5*1012/L; p<0.01), and hematocrit [41.2±2.2% vs. 27.2±2.0; p<0.01]. Moreover, treated CA animals had reduced spleen weight [130±5mg vs. 310±21mg; p <0.01], as well as reduced extra-medullary hematopoiesis in the liver [0.7±0.1% (n=4) vs. 6.0±0.9% (n=5); p<0.01] and spleen [6.6±1.8 (n=4) vs. 23.1±1.4 (n=3); p<0.05]. qPCR analysis demonstrated increased gene expression of human beta globin (figure A) and reduced expression of human gamma globin in blood and bone marrow of IUGT offspring. HPLC analysis confirmed these findings at protein level (figure B). The average vector copy number in the liver was 0.1. Conclusions IUGT resulted in phenotypic normalization in a heterozygous humanized mouse model of CA. Increased levels of beta globin and associated down-regulation of gamma globin is consistent with a switch from fetal to adult human hemoglobin, confirming successful prenatal correction of the genetic defect. Figure A. Quantification of human beta globin mRNA using qPCR (*p<0.01) Figure A. Quantification of human beta globin mRNA using qPCR (*p<0.01) Figure B. HPLC analysis of peripheral blood hemolysates of control versus IUGT treated. Figure B. HPLC analysis of peripheral blood hemolysates of control versus IUGT treated. Disclosures No relevant conflicts of interest to declare.

Introduction: Intestinal atresia is an uncommon but challenging disease that require a high level of suspicion for timely diagnosis and expeditious treatment. Its incidence ranges anywhere from 3.4 per 10,000 to 1 per 66,000 live births. Herein we present a comprehensive review of the various presentations of Intestinal Atresia and provide an algorithm for its evaluation. Methods: A review of modern English Language in Index databases (PubMed, SCOPUS, EMBASE, MEDLINE, etc) in the English language was preformed. The etiology, pathophysiology, and management of the intestinal atresia at different levels of the intestinal tract was studied. Results: Atresia is often diagnosed soon after birth and requires a multidisciplinary approach for optimal outcomes. Duodenal atresia is associated with many congenital anomalies and requires a multisystem workup once diagnosed. Jejuno-ilealatresia is the most common intestinal atresia and has fewer associated congenital defects than duodenal atresia. Colonic atresia is the rarest of the intestinal atresias but often has the best outcome as long as it is promptly diagnosed and treatment is not delayed. Introduction Atresia of the small and large intestines is a challenging problem. The 2017 National Birth Defects Prevention Network data brief described the incidence of small bowel atresia as 3.4 per 10,000 live births and the incidence of large bowel atresia as up to 1 per 66,000 live births. There are numerous types of intestinal atresia that were first described by Bland-Sutton in 1889. His description was later expanded upon by Louw and Barnard in 1955 who proposed the vascular infarct etiology of jejunal, ileal, and colonic atresias. Their classification system was further subdivided by Grosfeld in the 1970s and is the system that is used today. Each can be a cause of significant morbidity and mortality in the neonatal population without early diagnosis and intervention. A multidisciplinary approach to diagnosis and management of these neonates is necessary for optimal outcomes. Although pathophysiology is slightly different with each type of atresia, they can have a similar presentation. All of the variations typically present with signs of bowel obstruction but can present a different days of life. Respiratory distress can result from a distended abdomen, and dehydration secondary to emesis and poor enteral absorption are also common. Neonates are particularly prone to dehydration with bowel obstruction secondary to their overall low total body volume. Intestinal atresias may also be associated with other congenital anomalies that will require additional workup. For example, duodenal atresia is commonly associated with Trisomy 21 and cardiac anomolies. Repair of each atresia is slightly different and will be discussed further in the following text. Prognosis of neonates with intestinal atresia is overall dependent on co-morbidities, timing of intervention, and length of bowel remaining status-post surgical repair. Intestinal Atresia Duodenal Atresia Pathophysiology Duodenal atresia is one of the many causes of neonatal intestinal obstructions with an incidence of 1 in 5000-10000 births(1). The most widely accepted etiology of duodenal atresia was proposed by Tandler in 1900 and is a lack of recanalization, or excessive endodermal proliferation, of the developing intestine around 8-10 weeks gestation, which differs from the vascular infarct etiology of other intestinal atresias(2). The duodenum has a duel vascular supply via the Celiac artery and the Superior Mesenteric artery which makes it less susceptible to ischemia. Duodenal atresia can range from complete separation of the intestines (Type III), to lumen separation while connected via a fibrous cord (Type II), or simple obstruction due to a mucosal web (Type I) such as the infamous “windsock deformity.” Clinical Presentation & Diagnosis Diagnosis can often be obtained prenatally via ultrasound which will demonstrate polyhydramnios&/or a dilated stomach. Post-natal clinical presentation is typically failure to tolerate feeds within the first 24-48 hours of life. The infant may have non-bilious or bilious emesis depending on whether the atresia is prior to the ampulla of vater or distal (80%) to it. If the atresia is present in the form of a mucosal web or stenosis then post prandial emesis may present later in life. Abdominal film will demonstrate the “double bubble” sign with gastric and duodenal gas separated by the pylorus. If there is gas distally a STAT upper GI study should be performed to rule out midgutvolvulus which requires emergent repair. A rare cause of distal gas on plain film could be an annular pancreas, which has been found in 23-33% of duodenal atresias(3,4). In the case of an annular pancreas if there is complete duodenal atresia but a patent duct of Santorini above and patent duct of Wirsung below then gas may pass distal to the atretic segment. However, the more common and more emergent diagnosis to exclude is that of malrotation with volvulus. Approximately 30% patients with duodenal atresia will have trisomy 21, but only 3% Trisomy 21 patients will have duodenal atresia(5). Other commonly associated anomalies include cardiac, malrotation, and annular pancreas. It is recommended that patients with duodenal atresia routinely have a cardiac and renal US, and if associated with Down’s Syndrome a rectal suction biopsy to rule out Hirschsprungs(5). Treatment Management of duodenal atresia is via surgical bypass or resection. Prior to surgery the patient should be medically optimized as best as possible which includes correction of electrolytes abnormalities, return to euvolemia, and proximal decompression via nasogastric tube. Given the association with trisomy 21 and cardiac anomalies it is recommended to have a pre-op echo and consultation with cardiology if timing permits. Perioperative antibiotics should consists of a second generation cephalosporin. If the neonate has had time to colonize the gut, >24 hours of life, anaerobic coverage should be added. Surgical repair consists of a duodenoduodenostomyvia either diamond-shaped anastomosis (transverse proximal incision with a longitudinal distal incision), side-to-side anastomosis, or even a duodeno-jenostomy(6,7). If there is a significant size discrepancy a tapering enteroplasty may be necessary. Traditionally this repair has been performed via laparotomy but with modern laparoscopic techniques minimally invasive surgery is an option for appropriate candidates at some centers (8,9). However, at the time of the operation the length of the bowel should be interrogated to rule out additional anomalies which is difficult to undertake laparoscopically. Dissection and anastomosis can be challenging due to the retroperitoneal position of the distal limb, therefore some surgeons will use surgical clips instead of sutures. During correction of the duodenal atresia it is important to exclude distal atresia of the small or large bowel, or correct malrotation which has been found 19-28% of patients with duodenal atresia(3,4). Management of a duodenal web has classically been resection via duodenotomy. Some authors propose also performing a duodenoduodenostomy for a mucosal web in order to decrease the risk of a stricture in the future. It was previously recommended to leave trans-anastomotic feeding tubes; modern data has shown this will prolong the time to PO intake and lengthen hospital stay. As such, trans-anastomotic feeding has been abandoned(10). Prognosis The overall prognosis of duodenal atresia depends on the concominate congenital anomalies. Isolated duodenal atresia has a good prognosis with the most likely complications being from the surgery itself, such as delayed gastric emptying or stricture. Most infants will resume enteral feeding within a few days post-op. If there is prolonged delayed gastric emptying (> 2 weeks) an upper GI with small bowel follow through should be obtained to rule out a distal stricture. Jejunal-Ileal Atresia Pathophysiology Jejuno-ilealatresia is the most common type of atresia and ranges from 1-5000 to 1-15000 births. There is an association with nearly 30% of infants having a low birth weight. While jejuno-ilealatresia is not generally associated with chromosomal anomalies, there is a suspected autosomal recessive pattern of inheritance to some type IV atresias that can present anywhere from the stomach to rectum(11). This is contrasted to duodenal atresia which has documented association with trisomy 21. Jejuno-ilealatresia is believed to be the result of a mesenteric arterial infarct during the 2nd or 3rd trimester that results in a lack of small bowel development. This theory has been supported since initial experiments were carried out by Louw& Barnard in Cape Town in the 1950s(12). Additional canine studies also supported this theory when ligation of canine mesenteric arteries in-utero led to the development of atresia(13). Although there are not associated chromosomal anomalies there are associated congenital anomalies. Approximately 10-16% of infants with gastroschisis will have some sort of jejunoilealatresia(14,15). It is also associated with volvulus, omphalocele, intussusception, or internal hernia(16-19). All of these can impede blood supply to the developing bowel and cause strangulation, thereby causing the vascular infarct necessary for the atresia to form The severity and timing of the infarct during development determine the extent of atresia, which is categorized according to the Louw Classification that was modified by Grosfeld (see table 1). The frequency and severity of each type is inversely related, and the morbidity/mortality expectedly increases with severity (15,20) Type I is the least severe and intestinal transit is simply blocked by an intraluminal membrane, such as a mucosal web. The serosa remains in continuity and there is no mesenteric defect. Type II atresias also lack a mesenteric defect but the bowel is connected via a fibrous cord. Type III atresias are further subdivided by Grosfeld. Type IIIa consists of a mesenteric gap and no connection between bowel segments. Type IIIb typically occurs just distal to the duodenojejunal flexure with the remaining small bowel coiled around the ileocolic artery giving it the classically described “apple peel” appearance. Type IV atresia also has a mesenteric defect but has multiple atresias and segments of bowel in discontinuity and has often been described as a “string of sausages”. Clinical Presentation & Diagnosis Jejuno-ilealatresia is associated with fewer congenital anomalies than duodenal atresia due to its occurrence later in development. It will present as abdominal distention and bilious emesis of the neonate and should be treated as an emergency given the similar presentation of malrotation or a volvulus. Occasionally it can present as failure to pass meconium. Initial imaging should be an abdominal film which will demonstrate multiple loops of proximal bowel with air fluid levels and lack of gas in the colon and rectum. A contrast enema is often next to help differentiate a distal atresia from hirschsprungs disease, small left colon syndrome, or meconiumileus. It also evaluates the colon for atresia which is useful as the large bowel is difficult to evaluate intraoperatively. Colonic atresia can be definitively excluded if contrast is seen refluxing from colon into dilated loops of bowel. In the neonate colonic haustra are not prominent and may not be seen on plain film. Colon is best identified on place film by tracking the predicted location. Additional testing should be performed for cystic fibrosis given its high correlation (10%) in patients with jejuno-ilealatresia(14,21). Treatment Once the diagnosis of atresia has been established the patient should have a nasogastric tube for proximal bowel decompression and be adequately resuscitated before proceeding to the OR. Intra-op findings will dictate the final procedure to be performed but generally consists of resection of the atretic segments with primary anastomosis. While maintaining bowel length is critical, it is also imperative to minimize the amount of atretic or massively dilated bowel lest it cause a functional obstruction. As long as bowel length will not be excessively shortened it is recommended to resect the proximally atretic bowel(18,22,23). However, in patients where short gut is of concern a tapering enteroplasty may be necessary due to size mismatch and is preferred to formal resection of the dilated bowel(20). In the setting of Type IV atresia multiple anastomoses are preformed and often protected best as possible with a proximal stoma. In patients with gastroschisis and midgutatresia there remains controversy regarding optimum management. Current options include initial exteriorization of the bowel, primary anastomosis as previously discussed, or a multi-stage approach by placing the atretic segments into the abdominal cavity and closing the abdominal wall with a delayed definitive repair several weeks later(24-26). Patients with shortgut will often benefit from a lengthening procedure. One of the first such procedures was described by Bianchi in the 1980s and consists of serial longitudinal division of the dilated bowel. This creates hemiloops of bowel that are then anastomosed to each other in an isoperistaltic fashion(27). In 2003 a new procedure was described by Kim et. Al called serial transverse enteroplasty, or STEP(28). This procedure is technically less challenging than the Bianchi and consists of partial and equidistant bowel transections with a stapler to leave a 1-2cm lumen. Some of the advantages of STEP over the Bianchi include the ability to perform it when there is a foreshortened mesentery, and also to perform serial lengthening procedures once the bowel ages and increase in girth(29,30). When bowel lengthening procedures fail and there is persistant short bowel syndrome the patient must be on lifelong TPN unless a bowel transplant can be performed. Prognosis The overall prognosis of jejuno-ilealatresia is better than that of duodenal because there are fewer associated genetic anomalies but still depends on the type of atresia and associated congenital anomalies. Short bowel syndrome is most likely to occur in patient with Type IIIa, IIIb, and IV atresias due to the initially short overall length of bowel that is further decreased with the required anastomoses(4). The incidence of short gut syndrome is varied and can range from as low as 3% to high as 43% in some series(20,31). Colonic Atresia Pathophysiology Colonic atresia is the least common type atresia out of all of the intestinal atresias. The incidence of large bowel atresiais estimated to be from approximately 4.2 per 10,000 live births when combined with rectal atresia/stensis to 1 per 66,000 live births for only colonic atresia(32,33). The pathophysiology of colonic atresia is thought to be similar to jejunal-ilealatresia in that it is the result of anintrauterine mesenteric infarct. This theory has been reproduced in canine studies(12). Theories have also been proposed as to the mechanism of infarct, the vast majority of which point to an ischemic etiology. One case report cited the presence of an internal hernia with a defect through the falciformligament which subsequently leads to extrinsic mesenteric vascular obstruction(34). Strangulation secondary to gastroschisis has also been proposed as a mechanism to bowel injury resulting in colonic atresia(35-37). It has also been recently proposed that type II and IIIa right colonic atresias may form from constriction as the umbilical ring closes(38). Classification of colonic atresia parallels that of jejuno-ilealatresia. Clinical Presentation & Diagnosis Colonic atresia, like jejunal-ilealatresia, is not as commonly associated with congenital anomalies. However, there are a few anomalies that have been seen in neonates with colonic atresia including gastroschisis, Hirschsprung’s disease, and other intestinal atresias. It is thought that colonic atresia may be slightly more common in males than females (4:3)(21). The right colon is more commonly affected than the left colon. Colonic atresia on prenatal ultrasound has been describedin a case report as dilation of the colon with prominent haustrae, but findings are usually more vague such as polyhydramnios(39). Again, this finding is nonspecific and postnatal diagnosis is the most reliable. Neonates with colonic atresia will present with signs of obstruction such as bilious emesis and abdominal distention. They may also have failure to pass meconium(40). Often times in colonic atresia, diagnosis is delayed as abdominal distention and emesis typically occurs after several hours after onset of feeds (41). Work up typically begins with a plain radiograph of the abdomen in which one may see dilated loops of bowel, air fluid levels, and distal bowel gas. In order to further differentiate between colonic and ilealatresia, a contrast enema is the diagnostic test of choice. In colonic atresia, a contrast enema will reveal microcolon and absence of contrast in the proximal bowel. A suction biopsy may also be done to rule out Hirschsprung’s disease. Treatment Prior to surgical intervention, a neonate with a diagnosis of colonic atresia should have a nasogastric tube placed for gastrointestinal decompression. It may be necessary to replace nasogastric tube output with IV fluids. Dehydration can be a common complication in these neonates secondary to emesis and high NG output as the small bowel has limited resorbative capacity. Furthermore, colonic atresia can be overlooked until the infant suddenly stops tolerating feeds, develops abdominal distension & emesis, or has not passed meconium. The delay in diagnosis can result in worsened sepsis, electrolyte imbalance, and increased mortality(42-44). Therefore, care should be taken to maintain meticulous monitoring of electrolytes preoperatively. Surgical repair is usually achieved with resection of the proximal colon and creation of an ileo-colic anastomosis(40). An alternative approach is to create and initial stoma with delayed repair(21). Stoma creation is favored in left colon atresiawhereas resection and primary anastomosis is more common with right colon atresia(21).Although colonic atresia may sound similar to simple distal bowel obstruction, urgent repair of colonic atresia is necessary as a literature review of over 200 cases found that delay of surgical repair after 72 hours of life is associated with higher mortality rates(41). Additionally, if the patient has a competent ileocecal valve colonic atresia can act as a closed loop obstruction. Prognosis Complications from colonic atresia tend to be rare as these patients are less likely to have other anomalies. However, the presence of other anomalies expectedly results in a worse prognosis. Some retrospective epidemiologic studies have quoted the mortality rate at >20% but unfortunately these data include colonic along with rectal atresia and have multiple concomitant conditions(32). Most studies, including the experience of the authors of this chapter, demonstrate an excellent prognosis when colonic atresia is appropriately treated and overall mortality is exceedingly low(4,45). Typically, patients require TPN for just a few days post-procedure while enteral feeds are slowly resumed in the neonatal ICU. As with other repaired atresias, the length of bowel remaining will also affect overall prognosis. Conclusion Intestinal atresia can be a devastating disease but it is largely curable if promptly diagnosed and treated. Etiologies among the atresias differ with duodenal atresia being secondary to lack of recanalization or excessive proliferation in early development whereas jejunoal/ileal/colonicatresias result from a vascular accident later in development. Bilious emesis and abdominal distention are the most common presentation. The most common diagnostic finding on plain film is an abundance of gas proximally with a scarcity of gas distally. Due to its association and similar presentation to intestinal atresia the critical possibility of malrotation with volvulus must be religiously excluded given the emergent nature of that disease. When diagnosis is unclear, and malrotation is low on the differential, a contrast enema can help differentiate between distal atresia and other causes of obstruction (such as meconiumileus, hirschsprungs disease, etc). Intestinal atresia can occur anywhere in the gastrointestinal tract but the location and severity determine the treatment. The majority of complications from the intestinal atresias are from comorbid diseases – such as annular pancreas, gastroschisis, malrotation, Trisomy 21, cystic fibrosis – rather than from the atresia itself. Although most patients do well after treatment some will require life-long parenteral nutrition or repeated lengthening procedures depending on the amount of bowel remaining. Overall intestinal atresias are rare but they should always be on the differential for bilious emesis of the neonate. Conflict of Interest No conflicts of interest.

OBJECTIVES/SPECIFIC AIMS: If intranasal ketamine can be utilized for pain control in cancer patients, this could provide them with superior analgesia and better quality of life, without the risk of significant respiratory depression associated with opioid medications. We seek to obtain preliminary data via a clinical trial addressing safety, feasibility, and utility of this novel technique for the treatment of persistent uncontrolled cancer pain. These findings would be an important initial step towards testing the effectiveness of intranasal ketamine as a non-opioid medication for cancer pain used as potential maintenance outpatient therapy. These initial findings would be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients, and address the compelling need to identify new, successful management therapies for cancer pain. Specific Aims: 1. To evaluate (pharmacodynamic) effects of NAS ketamine on Patient Reported Outcomes (PROs), such as pain scores, side effects, depression, quality of life, and functional status. A clinical trial will be conducted where NAS ketamine will be given to a sample of patients with cancer related pain. Patient Reported Outcomes (PROs), such as pain scores, depression, quality of life, and functional status will be noted on Numerical Pain Rating Scale (NPRS), Montgomery Asberg Depression Rating Scale (MADRS), and Edmonton Symptom Assessment (ESAS), Eastern Cooperative Oncology Group (ECOG) and Patient Reported Outcome Measurement Information System (PROMIS) scales respectively. 1. To measure pharmacokinetics of NAS ketamine through analysis of ketamine and its metabolite norketamine to determine pharmacokinetic properties. During this clinical trial blood samples will be drawn at specified intervals and sent for analysis. 3. To determine opioid sparing effect of NAS ketamine. Opioid use will be measured by documenting use of rescue medications prior to and during the study and by evaluating total opioid consumption prior to and during the study. METHODS/STUDY POPULATION: Study sample: In the search for improved therapies for chronic cancer pain, medications with novel mechanisms of action have been sought. One such promising pharmacologic approach is ketamine. We specifically intend to measure utility of ketamine in patients with pain related to cancer or cancer treatment. Ketamine has shown to reverse central sensitization and opioid tolerance in rat models. Since ketamine is Scheduled III in United States and has abuse potential, we do not intend for ketamine to replace opioids, but use in patients who have failed opioid therapy. Since the investigators of the study practice at Emory, subjects will be from oncology and pain clinics (the supportive oncology clinic, oncology clinics, the pain clinic and Acute Pain Service) at Emory. The trial will be conducted at the Phase 1 Unit of the Winship Cancer Institute (WCI) at Emory. Subjects may be identified and contacted via telephone with information about the study prior to their next clinic appointment in order to allow time for them to consider the study. Eligibility criteria: Patients will be eligible to participate if they are: 1. Adults with uncontrolled cancer related pain a. Male and female subjects at least 18 years of age. b. Patients with uncontrolled pain related to cancer or cancer treatment. c. Uncontrolled pain will be defined as i. pain which persists for more than 7 days and is rated >/=4 on NPRS, and/or ii. use of breakthrough medication more than 4 times in 24 hours d. Failed other pain medications such non-steroidal anti-inflammatories such as ibuprofen, acetaminophen, opioids such as tramadol, hydrocodone, oxycodone etc. and antineuropathics such as gabapentin. 2. Able to provide informed consent a. Patients who are able to understand written and verbal English. Patients will be excluded from the study if they have any of the following: 1. Conditions increasing the risk of side effects from ketamine a. Conditions not safe due to cardiovascular effects of ketamine i. Presence of severe cardiac disease-EF <15% in patients with known history of cardiac disease ii. Uncontrolled Stage 2 hypertension or greater (systolic blood pressure > 160 and/or diastolic blood pressure >100) iii. Baseline tachycardia, HR >100 b. Conditions not safe due to potential effect of ketamine on intracranial and intraocular pressure i. Presence of elevated ICP ii. Uncontrolled glaucoma c. Presence of uncontrolled depression or other psychiatric comorbidity with psychosis 2. Conditions not safe due to potential side effects reported in ketamine abusers a. History of liver disease b. History of interstitial cystitis 3. Conditions where delivery of intranasal medications may be unreliable a. Active allergic or infectious rhinitis b. Patients with lesions of nasal mucosa 4. Conditions where fetus may be exposed to ketamine in utero (ketamine is category C medication) a. Pregnant women, nursing mothers and women of childbearing potential not using contraception known to be highly effective. b. Highly effective contraception methods include combination of any two of the following: Use of oral, injected or implanted hormonal methods of contraception or; Placement of an intrauterine device (IUD) or intrauterine system (IUS); Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; Total abstinence; Male/female sterilization. 5. Conditions with medication abuse potential a. Illicit substance abuse within the past 6 months b. Documented history of medication abuse/misuse (e.g. Unsanctioned dose escalation, broken opioid agreement etc.) 6. Conditions where ketamine metabolism may be altered, resulting in erroneous dose response relationship a. Clinical requirement for medications that are concurrent inducers or strong inhibitors of CYP3A4. CYP3A4 substrates are allowed. (Ketamine is metabolized by CYP3A4) Study sample limitations: Subject factors that may affect the final resultant study sample of subjects with full data for analysis. 1. Subjects who may not get pain relief with ketamine may not follow up and resulting incomplete data not eligible for analysis that may erroneously enhance positive effect of ketamine on pain relief. To account for this effort will be made to document the reason for lack of follow-up by contacting patient via telephone or at next scheduled clinic visit within Emory Healthcare. 2. Since patients coming to Emory are typically insured, the study will not adequately capture indigent population. It is not the intention of the current study to investigate differences in pain characteristics or responses of patients with insurance vs indigent population and will need to be addressed via future trials. Since this is a single center trial, the results of this trial might lack external validity required to support widespread changes in practice. This will be a pilot trial to figure out likely most efficacious dose. If this trial is successful, a multi-site randomized clinical trial will be conducted next. Primary Study Measures Primary exposure Intranasal Ketamine for cancer related pain Ketamine is an FDA approved anesthetic with amnesic, analgesic, dissociative, and sedative properties. It is unique among anesthetic agents in that it does not depress cardiovascular and respiratory systems. Ketamine is a noncompetitive, antagonist of N-methyl-D-aspartate (NMDA) receptors that blocks the NMDA channel in the open state by binding to the phencyclidine (PCP) site located within the lumen of the channel. Antagonism of NMDA receptors produces antinociception of persistent or neuropathic pain in animal models and analgesia in pain states in humans. The NMDA receptor is believed to play a role in the development of opioid tolerance and ketamine has been shown in a rat model to prevent fentanyl-induced hyperalgesia and subsequent acute morphine tolerance 5. Ketamine also interacts at a number of other receptor sites to block pain. Some of these sites include voltage-sensitive calcium channels, depression of sodium channels, modulation of cholinergic neurotransmission, and inhibition of uptake of serotonin and norepinephrine. Ketamine also interacts with kappa and mu opioid receptors; however, in humans, naloxone, an opioid antagonist, does not antagonize the analgesic effects of ketamine. Safety and efficacy of ketamine as an anesthetic and analgesic agent is well-documented 2-4. Ketamine is not labeled by the FDA as an analgesic agent. Low (subanesthestic) doses of ketamine have minimal adverse impact upon cardiovascular or respiratory function but produce analgesia and modulate central sensitization, hyperalgesia, and opioid tolerance. Cancer pain, especially in end stages, can be very complicated and is mediated by a variety of pathways: visceral, nociceptive, neuropathic and central. If ketamine can be utilized for pain in end stage cancer patients, this could provide them with superior analgesia and better quality of life, without the risk of significant respiratory depression associated with opioid medications. One of the challenges that we face with ketamine is the route of administration. The most common route is intravascular or intramuscular. Although it has been given orally and rectally, the bioavailability of ketamine when given via these routes is limited to 20-30%. Intranasal (NAS) administration has advantages of being needle free method of administration with potential for outpatient therapy. It lacks hepatic first pass effect resulting in higher bioavailability compared to oral route. Large surface area, uniform temperature, high permeability and extensive vascularity of the nasal mucosa facilitate rapid systemic absorption of intranasal administered drugs 6. In the pilot trial conducted by the study investigators, single dosage of intranasal ketamine has been shown to be feasibility and effective option for temporary pain reduction in patients with cancer related pain. The investigators now seek to obtain feasibility and efficacy data on long-term use of intranasal ketamine for cancer related pain. Ketamine is a scheduled III medication. A physician with a DEA license can order intranasal ketamine from a compounding pharmacy. Primary outcome of interest: Pain scores will be recorded on Numerical Pain Rating Scale (NPRS) at regular intervals throughout the study. NPRS is the most responsive tool to document pain intensity when compared to Visual Analogue Scale (VAS) and Visual Rating Scale (VRS) for measuring pain, 7 showing higher compliance rates, better responsiveness, ease of use, and good applicability relative to VAS/VRS8. Minimal clinically important differences (MCIDs) for pain ratings varies substantially based on patient population and statistical technique used, range of 0.4 to 3.7 points has been reported as a MCID. In general, improvements of pain severity</=1.5 points on NPRS could be seen as clinically irrelevant 9-13. Above that value, the cutoff point for “clinical relevance” depends on patients’ baseline pain severity, and ranges from 2.4 to 5.3 11-13. Higher baseline scores require larger raw changes to represent clinically important differences 14. Primary aim: To determine efficacy of intranasal ketamine in reducing cancer related pain. A clinical trial will be conducted to determine effect of intranasal ketamine on cancer related pain. Pain scores will be recorded on Numerical Pain Rating Scale (NPRS) at regular intervals throughout the study. Minimal clinically important differences (MCIDs) for pain ratings varies substantially based on patient population and statistical technique used, range of 0.4 to 3.7 points has been reported as a MCID. In general, improvements of pain severity</=1.5 points on NPRS could be seen as clinically irrelevant 9-13. Above that value, the cutoff point for “clinical relevance” depends on patients’ baseline pain severity, and ranges from 2.4 to 5.3 11-13. Higher baseline scores require larger raw changes to represent clinically important differences 14. Several clinical trials for pain have reported a reduction of 2 points on NPRS to be clinically important.15-17 Therefore for the purposes of this study, MCID of 2 was used for sample size calculations. A prior research study done by Carr et al. studied effects of intranasal ketamine for breakthrough pain in patients with chronic pain of various etiologies. 18 Total number of subjects in this study was 20 (4 of these had cancer related pain).This study demonstrated a mean reduction of 2.7 units on NPRS (P<0.0001), with standard deviation of 1.87. Since MCID is 2, effect size using this (MCID/SD) = 1.05. Power and sample size table: Assumptions: 1. T-test is the appropriate test (may not be the appropriate test since we have a small sample size and may not be able to assume normality of means based on the central limit theorem) 2. Distribution of reductions in pain score is normal 3. Effect size of 1.05 is clinically meaningful; Sample Size: A sample size of 7 from a population of 20 (in the study done by Carr etal.) achieves 80% power to detect a NPRS difference of −2 between the null hypothesis mean of 0.0 and the alternative hypothesis mean of 2 with an estimated standard deviation (SD) of 1.87 and with a significance level (alpha) of 0.05 using paired t-test assuming that the actual distribution is normal. We will include 10 patients to account for the possibility that the observed pain reduction in the current study may be different than the study done by Carr, as in this study patients were given ketamine for breakthrough pain, as opposed to for baseline pain. We will enroll 25 patients in the study to account for potential dropouts. RESULTS/ANTICIPATED RESULTS: Majority of subjects experienced the largest decrease in their pain with the 10mg IV dose. Side effects included nausea/vomiting and a feeling of unreality. All side effects resolved by the end of each study visit. No severe adverse events occurred. DISCUSSION/SIGNIFICANCE OF IMPACT: Further study is required to elucidate safety of NAS ketamine with long term use for cancer related pain.

Abstract Background and objective Studies linking early life exposure to air pollution and subsequent impaired lung health have focused on chronic, low-level exposures in urban settings. We aimed to determine whether in utero exposure to an acute, high-intensity air pollution episode impaired lung function 7-years later. Method We conducted a prospective cohort study of children who lived in the vicinity of a coalmine fire. Respiratory function was measured using the forced oscillation technique (FOT). Z-scores for resistance at 5 Hz (R5), reactance at 5 Hz (X5) and area under the reactance curve (AX) were calculated. Two sets of analyses were conducted to address two separate questions: (1) whether mine fire exposure (a binary indicator; conceived after the mine fire vs in utero exposed) was associated with the respiratory Z-scores; (2) whether there was any dose–response relationship between fire-related PM2.5 exposure and respiratory outcomes among those exposed. Results Acceptable lung function measurements were obtained from 79 children; 25 unexposed and 54 exposed in utero. Median (interquartile range) for daily average and peak PM2.5 for the exposed children were 4.2 (2.6 – 14.2) and 88 (52—225) µg/m3 respectively. There were no detectable differences in Z-scores between unexposed and exposed children. There were no associations between respiratory Z-scores and in utero exposure to PM2.5 (daily average or peak). Conclusion There was no detectable effect of in utero exposure to PM2.5 from a local coalmine fire on post-natal lung function 7-years later. However, statistical power was limited.

Abstract Background Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) from a mine fire, background PM2.5, and allergic sensitisation later in childhood. Methods We measured specific immunoglobulin E (IgE) levels for seven common aeroallergens as well as total IgE levels in a cohort of children who had been exposed to the Hazelwood coal mine fire, either in utero or during their first two years of life, in a regional area of Australia where ambient levels of PM2.5 are generally low. We estimated personal exposure to fire-specific emissions of PM2.5 based on a high-resolution meteorological and pollutant dispersion model and detailed reported movements of pregnant mothers and young children during the fire. We also estimated the usual background exposure to PM2.5 at the residential address at birth using a national satellite-based land-use regression model. Associations between both sources of PM2.5 and sensitisation to dust, cat, fungi, and grass seven years after the fire were estimated with logistic regression, while associations with total IgE levels were estimated with linear regression. Results No association was found between the levels of exposure at either developmental stage to fire-related PM2.5 and allergic sensitisation seven years after the event. However, levels of background exposure were positively associated with sensitisation to dust (OR = 1.90, 95%CI = 1.12,3.21 per 1 μg/m3). Conclusions Chronic but low exposure to PM2.5 in early life could be more strongly associated with allergic sensitisation in childhood than time-limited high exposure levels, such as the ones experienced during landscape fires.

Abstract Background X-linked sideroblastic anaemia (XLSA) is commonly due to mutations in the ALAS2 gene and predominantly affects hemizygous males. Heterozygous female carriers of the ALAS2 gene mutation are often asymptomatic or only mildly anaemic. XLSA is usually characterized by microcytic erythrocytes (reduced mean corpuscular volume (MCV)) and hypochromia, along with increased red cell distribution width. However, in females with XLSA the characteristic laboratory findings can be dimorphic and present with macrocytic (elevated MCV) in addition to microcytic red cells. Case presentation We report a case of fetal anaemia, presenting in the early third trimester of pregnancy, in a female fetus. Ultrasound findings at 29 weeks were of cardiomegaly, prominent umbilical veins, a small rim of ascites, and mean cerebral artery peak systolic velocity (PSV) value above 1.5 Multiples of the Median (MoM). She underwent non-invasive prenatal testing that determined the rhesus genotype of the fetus to be rhesus B negative. No red blood cell antibodies were reported. Other investigations to determine the underlying cause of fetal anaemia included microarray comparative genomic hybridization, serology to exclude congenital infection and a peripheral blood film and fetal bilirubin to detect haemolysis. The maternal grandmother had a history of sideroblastic anaemia diagnosed at the age of 17 years. The mother had mild macrocytic anaemia with haemoglobin of 10.4 g/dl and MCV of 104 fl. The fetal anaemia was successfully treated with two in utero transfusions (IUTs), and delivery occurred via caesarean section at 37 weeks of gestation. The red cell gene sequencing in both the mother and fetus were heterozygous for an ALAS2 mutation causing in utero manifestations of XLSA. The haemoglobin on discharge to the local hospital at five days of age was 19.1 g/dl. Subsequently, the infant became anaemic, requiring regular 3–4 monthly blood transfusions and demonstrating overall normal development. Her anaemia was unresponsive to pyridoxine. Conclusions This is one of four cases reporting multiple female members presenting with discordant clinical features of XLSA from being entirely asymptomatic to hydropic in utero. Our report is novel in that there are no previous cases in the literature of anaemia in a female fetus heterozygous for ALAS2 mutation.

Abstract Background Systemic juvenile xanthogranuloma is a very rare disease typically presents as skin lesions with yellow papules or nodules and is sometimes fatal. We report a case of congenital neonatal systemic juvenile xanthogranuloma with atypical skin appearance that made the diagnosis difficult. Case presentation A preterm Japanese female neonate with prenatally diagnosed fetal hydrops in-utero was born with purpuric lesions involving the trunk and face. Since birth, she had hypoxemic respiratory failure, splenomegaly, anemia, thrombocytopenia, coagulopathy, and was transfusion dependent for red blood cells, fresh frozen plasma, and platelets. Multiple cystic lesions in her liver, part of them with vascular, were detected by ultrasound. A liver biopsy was inconclusive. A skin lesion on her face similar to purpura gradually changed to a firm and solid enlarged non-yellow nodule. Technically, the typical finding on skin biopsy would have been histiocytic infiltration (without Touton Giant cells) and immunohistochemistry results which then would be consistent with a diagnosis of systemic juvenile xanthogranuloma, and chemotherapy improved her general condition. Conclusions This case report shows that skin biopsies are necessary to detect neonatal systemic juvenile xanthogranuloma when there are organ symptoms and skin eruption, even if the skin lesion does not have a typical appearance of yellow papules or nodules.

ImportancePsychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.ObjectiveTo evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.Design, Setting, and ParticipantsThis cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.ExposuresOne or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Main Outcomes and MeasuresAny major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.ResultsA total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.Conclusions and RelevanceIn this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.

Water pollution is one of the environmental challenges to be surmounted to avoid global public health hazard. Due to the complex chemical structure, azo dyes in industrial effluent have a long shelf life and are toxic to aquatic creatures even at low quantities. In this study, the decolourisation of azo dye, methylene blue (MB) using locally sourced photocatalyst, eggshell ash (ESA) under solar ultra-violet (UV) radiation was investigated. In order to test the photo-activities of ESA, a similar study was performed without sunlight. ESA was characterised using Fourier transform infrared (FTIR) spectroscopy. Maximum decolourisation efficiencies (96% with sunlight and 77% without sunlight) were recorded at contact time of 120 minutes and 1.5 g/dm3 of catalyst. The data obtained were fitted into kinetics models and adsorption isotherms. According to the findings, pseudo-second order kinetics model best described the process with rate constant of 0.1529 g/mg.min and regression value, R2 of 0.9934. Intra-particle diffusion model showed that the uptake of MB was more of film diffusion than the intra-particle diffusion. The adsorption isotherm fitted better into Langmuir isotherm with adsorption capacity of 0.0213 dm3/mg and R2 of 0.9957, while the Temkin isotherm indicates that the process was a physical adsorption as the heat of sorption value (0.0015 Kcal./mol.) was less than 1.0 kcal/mol. Generally, the study revealed that ESA was a suitable photocatalyst for the decolourisation of azo dyes under solar UV rays.

Abstract Background The 2014 Hazelwood coal mine fire was an unprecedented six-week severe smoke event in the Latrobe Valley, southeastern Australia. We aimed to determine whether maternal exposure to fine particulate matter (PM2.5) attributable to the event was associated with adverse fetal growth or maturity, including birthweight, small for gestational age, term low birthweight or preterm birth. Methods A cohort of babies born within the affected region was defined used administrative perinatal data. Maternal average and peak PM2.5 was assigned to residential address at time of delivery using a chemical transport model. Maternal, infant, meteorological and temporal variables were included in final linear and log-binomial regression models. Results 3,591 singleton livebirths were included; 763 were exposed in utero. Average PM2.5 exposure was 4.4 µg/m3 (IQR 2.1 µg/m3); average peak was 45.0 µg/m3 (IQR 35.1 µg/m3). No association between PM2.5 and fetal growth or maturity was observed. Gestational diabetes mellitus was an effect modifier in the relationship; babies of exposed gestational diabetic mothers were 97 grams heavier per 10 µg/m3 increase in average PM2.5 exposure (95%CI 74, 120 grams), compared to mothers without gestational diabetes. Conclusions Maternal PM2.5 exposure from a smoke event was not associated with adverse fetal growth or maturity. There was a trophic response amongst babies of mothers with gestational diabetes. Key messages Babies born to mothers with gestational diabetes may be more susceptible to the effects of smoke events on birthweight.

Abstract In studies of hominin adaptations to fire use, the role of the aryl hydrocarbon receptor (AHR) in the evolution of detoxification has been highlighted, including statements that the modern human AHR confers a significantly better capacity to deal with toxic smoke components than the Neanderthal AHR. To evaluate this, we compared the AHR-controlled induction of cytochrome P4501A1 (CYP1A1) mRNA in HeLa human cervix epithelial adenocarcinoma cells transfected with an Altai-Neanderthal or a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage. We observe no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR, whereas a 150–1,000 times difference was previously reported in a study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our study exemplifies that expression in a homologous cellular background is of major importance to determine (ancient) protein activity. The Neanderthal and modern human dose–response curves almost coincide, except for a slightly higher extrapolated maximum for the Neanderthal AHR, possibly caused by a 5′-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study based on 18 relevant genes in addition to AHR, which concluded that efficient detoxification alleles are more dominant in ancient hominins, chimpanzees, and gorillas than in modern humans.

Short-duration facilities have been used for the past 35 years to obtain measurements of heat transfer, aerodynamic loading, vibratory response, film-cooling influence, purge flow migration, and aeroperformance for full-stage, high-pressure turbines operating at design-corrected conditions of flow function, corrected speed, and stage pressure ratio. This paper traces the development of experimental techniques now in use at The Ohio State University (OSU) Gas Turbine Laboratory (GTL) from initial work in this area at the Cornell Aeronautical Laboratory (CAL, later to become Calspan) from 1975 through to the present. It is intended to summarize the wide range of research that can be performed with a short-duration facility and highlight the types of measurements that are possible. Beginning with heat flux measurements for the vane and blade of a Garrett TFE 731-2 HP turbine stage with vane pressure-surface slot cooling, the challenge of each experimental program has been to provide data to aid turbine designers in understanding the relevant flow physics and help drive the advancement of predictive techniques. Through many different programs, this has involved collaborators at a variety of companies and experiments performed with turbine stages from Garrett, Allison, Teledyne, Pratt and Whitney (P/W), General Electric Aviation (GEA), Rocketdyne, Westinghouse, and Honeywell. The vane/blade interaction measurement and computational fluid dynamics (CFD) program, which ran from the early 1980s until 2000, provided a particularly good example of what can be achieved when experimentalists and computational specialists collaborate closely. Before conclusion of this program in 2000, the heat flux and pressure measurements made for this transonic turbine operated with and without vane trailing edge cooling flow were analyzed and compared to predictive codes in conjunction with engineers at Allison, United Technologies Research Center (UTRC), P/W, and GEA in jointly published papers. When the group moved to OSU in 1995 along with the facility used at Calspan, refined techniques were needed to meet new research challenges, such as investigating blade-damping and forced response, measuring aeroperformance for different configurations, and preparing for advanced cooling experiments that introduced complicating features of an actual engine to further challenge computational predictions. This required conversion of the test-gas heating method from a shock-tunnel approach to a blowdown approach using a combustor emulator to also create inlet temperature profiles, the development of instrumentation techniques to work with a thin-walled airfoil with backside cooling, and the adoption of experimental techniques that could be used to successfully operate fully cooled turbine stages (vane row-cooled, blade row-cooled, and proper cavity purge flow provided). Further, it was necessary to develop techniques for measuring the aeroperformance of these fully cooled machines.

The release of the film Fight Club (Dir. David Fincher, 1999) was met with an outpouring of contradictory reviews. From David Ansen’s [Newsweek] claim that “Fight Club is the most incendiary movie to come out of Hollywood in a long time” (Fight Club DVD insert) to LA Times’s Kenneth Turan who proclaimed Fight Club to be “…a witless mishmash of whiny, infantile philosophising and bone-crushing violence that actually thinks it’s saying something of significance” (Fight Club DVD insert), everyone, it seemed, needed to weigh in with their views. Whether you think the film is a piece of witless and excessive trash, or believe, as Fight Club novelist Chuck Palahniuk hopes “it would offer more people the idea that they could create their own lives outside the existing blueprint for happiness offered by society,” this is a film that people react strongly to (Fight Club DVD insert). Whether or not the film is successful in the new ‘blueprint’ area is debatable and one focus of this essay. It isn’t difficult to spot the focus of the film Fight Club. The title and the graphic, edgy trailers for the film leave no doubt in the viewer’s mind that this film is about fighting. But fighting what and why are the questions that unveil the deeper edge to the film, an edge that skirts the abyss of deep psychological schism: man’s alienation from man, society and self, and the position of the late twentieth century male whose gendered potentialities have become muted thanks to corporate cookie-cutter culture and the loss of a ‘hunter-gatherer’ role for men. In a nutshell, the film explores the psychic rift of the main character, unnamed for the film, but conventionally referred to as “Jack” (played by Ed Norton). Jack leads a life many late twentieth century males can identify with, a life without real grounding, focus or passion. It is the kind of life that has become a by-product of the “me” generation and corporate/consumer culture. Aside from Jack’s inability to find real satisfaction in his love life, friendships, job, or sense of self, he also suffers from an identity disorder. While there are few people who are unaware of the mind-numbing (and in some cases, audience-alienating) “twist” offered near the end of the film, it bears repeating that the compelling character of Tyler Durden (played by Brad Pitt) who shapes and influences the changes in Jack’s life is actually revealed near the end of the film as a manifestation of Jack’s alter ego. Jack and Tyler are the same person. The two conspire to start ‘Fight Club’, where men hit other men. Hard. The Club becomes an underground sensation, expanding to other communities and cities and eventually spawns the offshoot Project Mayhem whose goal it is to ultimately erase individual debt so everyone (all consumers) can start at zero. In order to manage this affair, several large buildings are slated for destruction by the Mayhem team. Of course no people will be in the buildings at the time, but all the records will be destroyed. This is the core of the film, but there are several other interesting sidelights that will become important to this discussion, including the lone female character Marla who becomes the love interest of Jack/Tyler, and the friend Bob, whom Jack meets during his insomniac foray into the seedy underworld of the self help meeting. The film itself seems to cry out for a psychoanalytic reading. Its thinly veiled references to Freudian concepts and subliminal tricks aside, it also makes the inner world of the protagonist its landscape and backdrop. In a film dominated by a psychological and psychical problem, psychoanalysis seems an excellent tool for delving more deeply into the symbols and attitudes of the piece. I have chosen both Kleinian object relations and Julia Kristeva’s understanding of abjection to help illuminate some issues in the film. Object relations helps to make clear both the divergence of personality and the emergence of a ‘repaired’ protagonist at the end of the film as Jack first creates and then destroys his alter ego. Kristeva initially explored abjection theory via literature in Powers of Horror (1982), but Barbara Creed’s Monstrous Feminine: Film, Feminism and Psychoanalysis (1993) opened wide the door for applications of the theory to film studies. Creed uses abjection to explore issues of gender in the horror film, focusing on the role and depiction of women as abject. Here, I have adapted some of her ideas and intend to explore the role of abjection in the male identification process. In this film fighting operates as both reality and metaphor, on both the physical and psychical levels, encompassing the internal and external fight within the mind and body of the protagonist. Jack’s main problem is a lack of concrete identity and self-realization. Numbed by his willing and eager participation in consumer culture and his tacit compliance with the gritty underworld of his job as an automotive ‘recall coordinator’, his life’s work is estimating the cost effectiveness of saving lives by calculating the cost of death. In Jack’s world, meaning is derived solely through the external—external products he consumes and collects. Jack’s consumer-based emasculation is expressed when he states, “Like so many others I had become a slave to the Ikea nesting instinct.” In this sentence he clarifies his disempowerment and feminisation in one swoop. Having few, if any, relationships with human beings, meaningful or otherwise, Jack never reaches a level of social maturity. His only solace comes from visiting anonymous help groups for the terminally ill. Although Jack is physically fine (aside from his insomnia) a part of him is clearly dying, as his sense of who he is in a postmodern culture is hopelessly mediated by advertisements that tell him what to be. In the absence of a father, Jack appears to have had no real role models. Made ‘soft’ by his mother, Jack exhibits a not so subtle misogyny that is illustrated through his relationship with fellow ‘tourist’ in the self-help circles, Marla Singer. Jack’s identity issues unfold via various conflicts, each of which is enmeshed in the club he starts that revolves around the physical pain of hand-to-hand, man-on-man combat. Jack’s conflicts with himself, others and society at large are all compressed within the theme and practice of fighting and the fight clubs he institutes. Fighting for Jack (and the others who join) seems the answer to life’s immediate problems. This essay looks deeply into Jack’s identity conflict, viewing it as a moment of psychic crisis in which Jack creates an alternate personality deeply steeped in and connected to the ‘abject’ in almost every way. Thus, Jack forces himself to confront the abject in himself and the world around him, dealing with abjection on several levels all with a view to expelling it to restore the ‘clean and proper’ boundaries necessary in the ‘whole’ self. Viewed though the lens of psychoanalysis, particularly Klein’s work on object relations and Kristeva’s work with abjection, allows a reading in which the film expresses the need for and accomplishment of a self-activated encounter with the abject in order to redraw ‘clean and proper’ boundaries of self. This film’s tag lines, ‘Mischief, Mayhem and Soap’—illustrate both the presence (Mischief, Mayhem) and function (Soap) of the abject—the interaction with the abject will lead to a ‘clean’ subject—a proper subject, a restored subject. Before continuing, a brief discussion of abjection and object relations and the ways in which they are utilized in this essay is essential here. One of Klein’s major propositions is that “the neonate brings into the world two main conflicting impulses: love and hate” (Mitchell 19). Each of these conflicting impulses must be dealt with, usually by either “bringing them together in order to modify the death drive along with the life drive or expelling the death drive into the outside world” (19). Along with this conflict arises the conflict of a primary relationship with the mother, which is seen as both satisfying and frustrating, and then later complicated with the addition of the father. The main conflicting love/hate binary is reflective of a number of ‘sets’ of dualities that surface when looking into the mother/child relationship. Besides love and hate, there is the ‘good’ and ‘bad’ mother, the mother as symbolic of both life and death, the symbolic (paternal) and semiotic (maternal), total oneness and total autonomy. The curious ‘split’ nature of the infant’s perception of the maternal figure recalls a kind of doppelganger, a doubling of the maternal (in positive and negative incarnations), that can be seen as abject. In the film, this informs the relationship between both Jack and Marla and Jack and Tyler, as I argue Tyler and Marla serve as parental substitutes at one part in the film. This is clarified in Jack’s statements about his relationship with the two of them: “My parents pulled this exact same act for years” and “I am six years old again, passing messages between parents.” This imaginary relationship allows Jack to re-experience some of his early identification processes, while effectively trading out the gender responsibilities to the point where Tyler symbolically takes the place of the ‘mother’ and Marla the place of the ‘father’. The result of this action is an excess of male gendered experiences in which Jack in crisis (emasculated) is surrounded by phalluses. Kristeva’s work with abjection is also important here. I am especially interested in her understanding of the mother/child relationship as connected with abjection, particularly the threat the mother represents to the child as wanting to return to a state of oneness. The abject functions in Fight Club as a means for the protagonist to re-configure his own autonomy. For Kristeva, the abject is that which is cast out in order that “I” may exist. It exists at the borders of the self and continually draws the subject into it. As the subject revolts and pulls away, its resistance cues the process of defining itself as separate, proper and autonomous. When the narrative of Jack’s life refuses to make sense to him, and his experiences seem like “a copy of a copy of a copy,” Jack turns inward for help. Kristeva says that the abject is “experienced at the peak of its strength when that subject, weary of fruitless attempts to identify with something on the outside, finds the impossible within” (5). Thus Jack ‘finds’ Tyler. The abject, [represented by Bob, Tyler and Marla in the film] is that which disturbs “identity, system, order. What does not respect borders, positions, rules” (Kristeva 4). As the abject is that which blurs boundaries borders and classification, the film itself is steeped in abject images and ideas. The discrete categories of inside/outside, asleep/awake, male/female, and self/other are continually troubled throughout the narrative. The two most confused binaries are male/female and self/other. As the film is about Jack’s own experience of emasculation it is not until the male/female gender issues are resolved that his self/other issues can be resolved. Through the re-ordering of gender he is able to take his place in society alongside Marla, finally viewed as not his mother or friend but lover. Jack Versus Himself: A Cult Of One Jack is able to re-vamp his personality through exposure to the abject and the replaying of certain key object relations moments in his childhood. He engages with this ‘inner child’ to reconnect with psychically difficult moments in which his ‘self’ emerged. Jack, however, twists the typical plot of maternal and paternal bonding in ways that speak to the underlying misogyny of the film and of late twentieth century society as well. While the story begins with both male and female characters in unnatural roles with unnatural and abject body parts, by the end of the film, these ‘abnormalities’ or abject objects are erased, ejected from the text so Jack is restored to the ‘safety’ of a compulsory heterosexuality. Bob, Tyler and Marla’s characters are three examples of gender twisting expressed in the film. In psychoanalytic literature, the child bonds first to the mother (via feeding from the breast and in-utero existence) and experiences a feeling of total oneness impossible to duplicate. Eventually the child seeks autonomy and breaks from the mother and her clinging ways with the help of the father and the phallus. So in basic terms, the female is abject, representing infantile regression and oneness, and the male represents taking the proper place in the symbolic order. When the female (mother) is denied, the male accepts his natural place in culture and society. However, in this film, Tyler (the male) is the abject presence in the text, that which threatens to consume and subsume the narrator’s personality. It is Marla, the phallic woman, who interposes herself in this dyad and becomes the correct choice for Jack, allowing him to proceed into ‘normal relations.’ Early in the film, Jack is unable to envision a female partner with whom he can open up and share, instead substituting Bob—and his doubly signified ‘bitch-tits’—as a locus of comfort. In Bob’s ample bosom, Jack finds the release he is looking for, though it is unnatural in more ways than one. The feminised Bob [testicular cancer patient] comforts and coddles Jack so much that he feels the same idyllic bliss experienced by the infant at the mother’s breast; Jack feels “lost in oblivion, dark and silent and complete.” That night he is able for the first time in months to sleep: “Babies don’t sleep this well.” This illustrates Jack’s longing for the safety and security of the mother, complicated by his inability to bond with a female, replaced with his deep need for identification with a male. Continuing the twist, it is Marla who foils Jack’s moment of infantile bliss: “She ruined everything” with her presence, Jack sneers. Jack’s regression to this infantile bliss with either man or woman would be perceived as abject, (disrupting system and order) but this particular regression is at least doubly abject because of Bob’s unnatural breasts and lack of testicles. Both Bob, and to some degree Tyler, offer abjection to Jack as a way of dealing with this complexities of autonomous living. While my argument is that Tyler takes the traditional ‘female’ role in the drama, as a figure (like Bob) who lures Jack into an unnatural oneness that must ultimately be rejected, it is true that even in his position as abject ‘female’ (mother), Tyler is overwhelmingly phallic. His ‘jobs’ consist of splicing shots of penises into films, urinating and masturbating into restaurant food and engaging in acrobatic sex with Marla. Since Marla, who occupies the position of father bringing Jack into society away from the influence of Tyler, is also coded phallic, Jack’s world is overwhelmingly symbolically male. This appears to be a response to the overwhelming physical presence of Jack’s mother of which Tyler comments, “We’re a generation of men raised by women. I am wondering if another woman is really the answer we need?” During this same scene, Jack clarifies his regressive dilemma: “I can’t get married, I am a thirty year old boy.” Thus while Tyler campaigns for a world without women, Jack must decide if this is the correct way to go. Immersion in the world of uber-maleness only seems to make his life worse. It is only after he ‘kills’ Tyler and accepts Marla as a partner that he can feel successful. In another help meeting, one of the guided meditations emphasizes his regression by asking him to go to his “cave” and locate his “power animal.” This early in the film, Jack can only envision his power animal as a rather silly penguin, which, although phallic to some extent, is undercut by the fact that it speaks with a child’s voice. In the next visualization of the ‘power animal’, the animal becomes Marla—clarifying her influence over Jack’s subconscious. The threat of Marla’s sexuality is on one level explored with Jack’s counterpart Tyler, the one who dares to go where Jack will not, but their encounters are not shown in a ‘natural’ or fully mature light. They are instead equated with childhood experimentation and regressive fantasies as Marla responds that she “hasn’t been fucked like that since grade school” and Tyler proclaims the relationship is mere “sportfucking.” It is Tyler who discovers Marla’s oversized dildo proudly displayed on a dresser, of which she states “Don’t worry its not a threat to you.” This phallicized Marla refers to herself as “infectious human waste,” clearly abject. Marla’s power must be muted before Jack can truly relate to her. This is illustrated in two separate ‘visions’ of sexual intercourse—one between Marla and Tyler early in the film in which Marla assumes the dominant position, and then later near the end of the film when the same encounter is replayed with Jack taking Tyler’s place, Marla now in the standard missionary position on her back: Proper. Jack’s struggle with self is played out via his relationship with Tyler (and Marla to some degree). Once Jack has been exposed to the various levels of abject behaviour offered by Tyler and Project Mayhem, he chooses to go it alone, no longer needing the double he himself created. After experiencing and rejecting the abject, Jack redraws his boundaries and cleanses his soul. Jack Versus Society—The Personal Is Political Jack’s personal struggle becomes political—and communal. Another attempt at forming identity, Fight Club is bound to fail because it offers not autonomy but a group identity substituted for an individual one. While Jack loathes his ‘single serving life’ before Fight Club, he must come to realize that a group identity brings more problems than solutions in an identity crisis. While the comfort of ‘oneness’ is alluring, it is also abject. As Jack is able to finally refuse the safely and oneness offered by Tyler’s existence, he must also deny the safety in numbers offered by Fight Club itself. The cult he creates swallows members whole, excreting them as the “all singing all dancing crap of the world.” They eat, drink and sleep Fight Club and eventually its ‘evolutionary’ offshoot, Project Mayhem. During his involvement with Fight Club and Project Mayhem, Jack is exposed to three levels of abjection including food loathing, bodily wastes, and the corpse, each of which threaten to draw him to the “place where meaning collapses” (Kristeva 2). Jack’s first experience involves Tyler’s (a)vocation as a waiter who urinates and probably masturbates into patrons’ food. This mingling of bodily wastes and nourishment represents the most elementary form of abjection: food loathing. While Jack appears amused at Tyler’s antics in the beginning, by the end of the film, he illustrates his movement closer to self-identification, by calling for “clean food, please” signalling his alliance with the clean and proper. Bodily wastes, the internal made visible, represent the most extended contact Jack has with the abject. These experiences, when what is properly outside ends up inside and vice versa, begin with bloody hand-to-hand combat, including Tyler’s vomiting of blood into the mouth of an unwilling Fight Club participant “Lou”, causing another witness to vomit as well. The physical aversion to abject images (blood, pus, excrement) is part of the redrawing of self—the abject is ejected –via nausea/vomiting. Kristeva explains: “I give birth to myself amid the violence of sobs, of vomit” (3). The images continue to pile up as Jack describes life in the Paper Street house: “What a shit hole.” The house slowly decomposes around them, leaking and mouldy, releasing its own special smell: the rot of a “warm stale refrigerator” mixed with the “fart smell of steam” from a nearby industrial plant. While at Paper Street, Tyler decides to make soap. Soap in itself is an agent of cleanliness, but in this context it is abject and defiled by being composed of human waste. In a deeply abject moment, Jack is accidentally covered in refuse that spills from a ripped bag full of human fat pilfered from a liposuction clinic. Even at this profoundly disturbing moment, Jack is unwilling to give up his associations with Tyler and Project Mayhem. It is only after his encounter with a corpse that he changes his tune. While Fight Club attempted to blur physical boundaries via hand-to-hand combat and exchange of blood and blows, Project Mayhem threatens the psychic boundaries of self, a deeper danger. While a loud speaker drones “we are all part of the same compost heap” and a fellow occupant reminds Jack “In project mayhem we have no names,” Jack realizes he is truly losing himself, not gaining strength. Mayhem’s goal of ‘oneness’, like the maternal and infant experience, is exposed via slogans like “you are not a beautiful and unique snowflake. You are the same decaying organic matter as everything else.” Tyler finally puts his cards on the table and asks Jack to “stop trying to control everything and just let go.” For Kristeva, “If dung signifies the other side of the border, the place where I am not and which permits me to be, the corpse, the most sickening of wastes, is a border that has encroached upon everything”(3). The corpse of Bob causes Jack to confront the boundaries of life and death, both spiritual and physical, as he opens his eyes to the damaging effects of the cult-like environment into which he has fallen. Jack’s momentary indecision morphs into action after Bob’s death becomes just one more mantra for the zombie-like Project Mayhemers to chant: “His name was Robert Paulson.” Jack’s internal and external struggles are compressed into one moment when he commits homo(sui)cide. Placing a gun in his mouth, he attempts to rid himself of Tyler forever, his final words to Tyler: “My eyes are open now”. At this point, Jack is psychically ready to take charge of his life and confidently eject the abject from the narrative of his life. He wants no more to do with Project Mayhem gang and is reunited with Marla with whom he finally appears ready to have a fully realized relationship. His masculinity and identity restoration are made blindingly apparent by the final splice in the film—the image of Marla and Jack hand in hand overlooking the new view out of the tower, spliced with the shot of a semi-erect penis—back to shot of Marla and Jack. The message is clear: Jack is a man, he has a woman, and he knows who he is because of it. While Fight Club novelist Palahniuk hopes the film offers options for life “outside the existing blueprint offered by society” (Fight Club DVD insert). On the other hand, it’s unclear how well the film pulls this off. On one hand, its lambasting of the numbing effects of blind and excessive consumerism seems well explored, it’s unclear what options really surface by the end of the film. Although many targeted buildings have been destroyed, through which the viewer can assume some or even most records of individual debt were erased, the building in which Marla and Jack stand (initially slated for destruction) remains. Perhaps this is meant to signify the impossibility of true financial equality in American society. But it seems to me that the more pressing issues are not the ones openly addressed in the film (that of money and consumerism) but rather the more internalised issues of self-actualisation, gender identity and contentment. In a postmodern space ripe for the redrawing and redefinition of gender stereotypes, this film carefully reinscribes not only compulsory heterosexuality but also the rigid boundaries of acceptable male and female behaviour. For this film, the safest route to repairing male identity and self-hood threatened by the emasculating practices of a consumer culture is a route back. Back to infantile and childhood fantasy. While it dances provocatively around the edges of accepting a man with ‘bitch tits’ and a woman with a dick, ultimately Bob is killed and Marla reclaimed by Jack in an ‘I’m ok you’re ok’ final scene: “Look at me Marla, I am really OK”. Jack’s immersion in an all male cult(ure) is eschewed for the comfort of real breasts. Works Cited Creed, Barbara. The Monstrous Feminine: Film, Feminism and Psychoanalysis. New York: Routledge, 1993. Fight Club. Dir. David Fincher. 1999. Fight Club DVD edition. Dir. David Fincher. 2000. Kristeva, Julia. Powers of Horror: An Essay On Abjection. New York: Columbia Press: 1982. Mitchell, Juliet. The Selected Melanie Klein. New York: The Free Press, 1986. Citation reference for this article Substitute your date of access for Dn Month Year etc... MLA Style Caldwell, Tracy M.. "Identity Making from Soap to Nuts" M/C: A Journal of Media and Culture 6.1 (2003). Dn Month Year < http://www.media-culture.org.au/0302/10-identitymaking.php>. APA Style Caldwell, T. M., (2003, Feb 26). Identity Making from Soap to Nuts. M/C: A Journal of Media and Culture, 6,(1). Retrieved Month Dn, Year, from http://www.media-culture.org.au/0302/10-identitymaking.html