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Spinal muscular atrophy with congenital bone fractures 2 (SMABF2), a type of arthrogryposis multiplex congenita (AMC), is characterized by congenital joint contractures, prenatal fractures of long bones, and respiratory distress and results from biallelic variants in ASCC1. Here, we describe an infant with severe, diffuse hypotonia, congenital contractures, and pulmonary hypoplasia characteristic of SMABF2, with the unique features of cleft palate, small spleen, transverse liver, and pulmonary thromboemboli with chondroid appearance. This infant also had impaired coagulation with diffuse petechiae and ecchymoses which has only been reported in one other infant with AMC. Using trio whole genome sequencing, our proband was identified to have biallelic variants in ASCC1. Using deep next generation sequencing of parental cDNA, we characterized alteration of splicing encoded by the novel, maternally inherited ASCC1 variant (c.297-8 T > G) which provides a mechanism for functional pathogenicity. The paternally inherited ASCC1 variant is a rare nonsense variant (c.466C > T; p.Arg156*) that has been previously identified in one other infant with AMC. This report extends the phenotypic characteristics of ASCC1-associated AMC (SMABF2) and describes a novel intronic variant that partially disrupts RNA splicing.

The global COVID-19 pandemic has claimed the lives of millions and disrupted nearly every aspect of human society. Currently, vaccines remain the only widely available medical means to address the cause of the pandemic, the SARS-CoV-2 virus. Unfortunately, current scientific consensus deems the emergence of vaccine-resistant SARS-CoV-2 variants highly likely. In this context, the design and development of broad-spectrum, small-molecule based antiviral drugs has been described as a potentially effective, alternative medical strategy to address circulating and re-emerging CoVs. Small molecules are well-suited to target the least-rapidly evolving structures within CoVs such as highly conserved RNA replication enzymes, and this renders them less vulnerable to evolved drug resistance. Examination of the vast literature describing the inhibition of RNA viruses by Amaryllidaceae alkaloids suggests that future, broad-spectrum anti-CoV drugs may be derived from this family of natural products.

Background Anaphylaxis is a serious and growing concern in the school setting as the prevalence of food allergies and food-induced severe allergic reactions continues to increase. Methods A cross-sectional, web-based survey was conducted regarding anaphylactic events that occurred during the 2014-2015 school year. Eligible schools were enrolled in the EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA), which provides free epinephrine auto-injectors to qualifying US schools. Participating schools completed a 29-item survey on anaphylactic event occurrence and treatment, epinephrine stock, school policies regarding anaphylaxis, school staff training, and school nursing coverage. Results Responses were provided by 12,275 schools. Epinephrine was administered on school property for 63.7% of reported anaphylactic events (1272/1998). In 38.5% (235/610) of events for which epinephrine was not used, antihistamines were cited as the reason. Only 59.4% of schools cited epinephrine as their standard first-line therapy for anaphylaxis. School nurses were most likely to be trained in anaphylaxis recognition and permitted to administer epinephrine; however, just 53.6% of schools had a full-time nurse on staff. Conclusions Process-related barriers to the appropriate use of epinephrine go beyond access to medication. Widespread staff training and review of school policies are needed to ensure that anaphylaxis is appropriately managed in schools.

Aim: The Townsville Hospital and Health Service is the regional referral centre for children in the north of Queensland. Aboriginal and Torres Strait Islander (ATSI) people make up 7–10% of the population. Increasing numbers of children with paediatric thoracic empyema (pTE) are being referred to Townsville Hospital and Health Service for management. This study aims to describe the incidence rates, epidemiology, microbiology and trends of this disease in North Queensland over a 10-year period. Methods: A retrospective chart review of all children (1 month to 16 years), admitted in the years 2007–2016, with community-acquired pTE was conducted. International Classification of Diseases codes were used to identify the patients. Epidemiological and microbiological data were extracted from records. Results: Of the 123 cases identified, incidence rates per 100 000 were 8.5 (95% confidence interval (CI) 8.4–8.6) in all children and much higher at 19.8 (95% CI: 19.5–21.9) in ATSI children. The under 5 years age group had the highest rate (24.5; 95% CI: 24.4–24.6). There was a progressive rise in incidence during the 10-year period, with the highest incidence of 15.2 (95% CI: 15.1–15.2) occurring in 2016. A pathogen was isolated in 76% of cases. Non-multi-resistant methicillin-resistant Staphylococcus aureus was the most common pathogen isolated in 22 of 64 ATSI children (34%), while Streptococcus pneumoniae was the most common pathogen isolated in 27 of 59 non-ATSI children (46%). Conclusions: A high and increasing incidence of pTE in North Queensland is being observed. ATSI children have higher incidence rates and are more likely to have non-multi-resistant methicillin-resistant Staphylococcus aureus as a causative agent.

Objective To determine the effect of secondary penicillin prophylaxis on echocardiographic diagnosed valvular changes in patients with rheumatic heart disease or history of acute rheumatic fever in the Townsville Health district. Design Patients with known were identified from the North Queensland register, serial echocardiogram results and number of secondary penicillin prophylaxis doses received in 2014 were collated. Descriptive statistics were utilised. Setting Townsville Hospital and outreach clinics within the Townsville Health catchment zone. Participants All patients diagnosed with acute rheumatic fever or rheumatic heart disease between 2010 and October 2013 who had serial echocardiograms prior to and post commencement of secondary penicillin prophylaxis were included. All patients were of Aboriginal or Torres Strait Islander descent. Main outcome measure Progression of echocardiographic valvular changes and association with secondary penicillin prophylaxis compliance. Compliance with secondary penicillin prophylaxis among the study population was a secondary outcome measure. Results Twenty-three patients were recruited. Only those patients who were compliant with secondary penicillin prophylaxis had any improvement in valvular changes on echocardiogram. Four of six patients without any baseline valvular involvement developed new valvular changes. Seventy percent of patients received >75% of secondary penicillin prophylaxis doses. Conclusions This small study of patients in Townsville suggests that with good secondary penicillin prophylaxis compliance there is regression of some cardiac lesions over time in people with rheumatic heart disease. Furthermore the natural history of acute rheumatic fever in the Indigenous population is progressive requiring strict adherence to secondary penicillin prophylaxis. Prospective studies or use of data from the nationwide RHD register and standardised reporting of cardiac echocardiograms will provide more robust evidence.

Field size distributions and their changes have not been studied over large areas as field size change datasets are not available. This study quantifies agricultural field size changes in a consistent manner using Landsat satellite data that also provide geographic context for the observed decadal scale changes. Growing season cloud-free Landsat 30 m resolution images acquired from 9 to 25 years apart were used to extract field object classifications at seven sites located by examination of a global agricultural yield map, agricultural production statistics, literature review, and analysis of the imagery in the US Landsat archive. High spatial resolution data were used to illustrate issues identifying small fields that are not reliably discernible at 30 m Landsat resolution. The predominant driver of field size change was attributed by literature review. Significant field size changes were driven by different factors, including technological advancements (Argentina and USA), government land use and agricultural policies (Malaysia, Brazil, France), and political changes (Albania and Zimbabwe). While observed local field size changes were complex, the reported results suggest that median field sizes are increasing due to technological advancements and changes to government policy, but may decrease where abrupt political changes affect the agricultural sector and where pastures are converted to arable land uses. In the limited sample considered, median field sizes increased from 45% (France) to 159% (Argentina) and decreased from 47% (Brazil) to 86% (Albania). These changes imply significant impacts on landscape spatial configuration and land use diversity with ecological and biogeochemical consequences.

Summary Parasite ova caused to accumulate in a single microscopic field simplifies monitoring soil-transmitted helminthiasis by optical microscopy. Here we demonstrate new egg-accumulating geometries based on annular menisci formed on the surface of a wetted cone. Fluidic features extracted from profile images of the system provided mathematical representations of the meniscus gradient that were compared quantitatively to numerical solutions of an axisymmetric Young–Laplace equation. Our results show that the governing dynamics of these systems is dominated by the surface tension of the fluid. These image analysis and mathematical tools provide simple quantitative methods for system analysis and optimization. Lay Description The diagnosis of gastrointestinal worms in animals and people by the visual identification of microscopic nematode eggs in stool can be simplified using of a specially designed fluid cell. The fluid cell collects the eggs at a specified location and a single microscope image showing the collected eggs can be recorded and transmitted for remote analysis. This process removes the manual searching of traditional microscope slides and allows remote location diagnosis of parasite disease. The fluid cell uses the natural curvature of a liquid droplet to passively direct the parasite eggs to the collection area. Using simple image analysis and mathematical modeling tools we have developed a better understanding of the key features of the liquid curvature in one configuration of the fluid cell. These tools can be applied to other configurations of fluid cell to further improve parasite diagnosis by optical microscopy.

Position effects due to disruption of distant cis-regulatory regions have been reported for over 40 human gene loci; however, the underlying mechanisms of long-range gene regulation remain largely unknown. We report on two patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) caused by overlapping genomic deletions that included a distant FOXF1 transcriptional enhancer mapping 0.3 Mb upstream to FOXF1 on 16q24.1. In one patient with atypical late-onset ACDMPV, a ∼1.5 Mb deletion removed the proximal 43% of this enhancer, leaving the lung-specific long non-coding RNA (lncRNA) gene LINC01081 intact. In the second patient with severe neonatal-onset ACDMPV, an overlapping ∼194 kb deletion disrupted LINC01081. Both deletions arose de novo on maternal copy of the chromosome 16, supporting the notion that FOXF1 is paternally imprinted in the human lungs. RNAi-mediated knock-down of LINC01081 in normal fetal lung fibroblasts showed that this lncRNA positively regulates FOXF1 transcript level, further indicating that decrease in LINC01081 expression can contribute to development of ACDMPV.

Background Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. Methods We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006–12). Eligible women were aged 18–40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. Results There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced. Conclusions We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.

We describe a simple device that volumetrically samples poured liquids and draws buoyant materials into a single field of view for quantitative particle microscopy. Our approach relies on the formation of axisymmetric menisci and computational models of the static fluid developed using surface evolver showed close agreement with experiment. The apparatus was evaluated by counting pollen and demonstrated utility for the field analysis of microparticles.

The Academy of Nutrition and Dietetics (Academy) and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) recommend that a standardized set of diagnostic characteristics be used to identify and document adult malnutrition in routine clinical practice. An etiologically based diagnostic nomenclature that incorporates a current understanding of the role of the inflammatory response on malnutrition's incidence, progression, and resolution is proposed. Universal use of a single set of diagnostic characteristics will facilitate malnutrition's recognition, contribute to more valid estimates of its prevalence and incidence, guide interventions, and influence expected outcomes. This standardized approach will also help to more accurately predict the human and financial burdens and costs associated with malnutrition's prevention and treatment and further ensure the provision of high-quality, cost-effective nutrition care.

In one prospective cohort study, a diagnosis of asthma was associated with an increased risk of mortality in individuals with sickle cell anemia or HbSS. However, a direct relationship between death and asthma exacerbation could not be documented. This report examines two adolescents with sickle cell disease (SCD) who died during worsening symptoms consistent with asthma. Autopsies in both individuals demonstrated pulmonary airway smooth muscle hyperplasia, basement membrane thickening, and eosinophilia, consistent with bronchial asthma. Individuals with SCD and asthma warrant ongoing education, treatment, and surveillance for life-threatening complications of asthma. Pediatr Blood Cancer 2011;56:454–457. © 2010 Wiley-Liss, Inc.

Aims: To review and present the most important issues related to kidney disease in Aboriginal, Torres Strait Islander,Maori and Pacific Islander children from Australia and New Zealand. Methods: A review of medical literature about: 1. incidence of kidney disease in Indigenous children in Australia and New Zealand, especially where rates are different from the general populations, 2. factors in early life which increase risk for chronic kidney disease in adult life, and 3. early identification and primary and secondary interventions in childhood which may prevent chronic kidney disease in adults. Results: Kidney diseases, both acute and chronic are more common in Maori, Pacific Islander, Australian Aboriginal and Torres Strait Islander people. The reasons are multiple and include genetic, environmental and socio-economic factors. In childhood post streptococcal glomerulonephritis, haemolytic uraemic syndrome, renal stones and acute kidney injury all occur at higher frequency in at least some of the Indigenous populations. Chronic kidney disease CKD occurs more commonly, and at a younger age in Indigenous than non Indigenous people. Factors involved may include reduced nephron endowment at birth, and subsequent insults including nephritis, obesity, and early onset type 2 diabetes, as well as underlying socioeconomic and environmental determinants. Conclusion: A lifecourse understanding allows one to conceptualise multiple risk factors and target interventions.

Aim: Child exposure to tobacco smoke is detrimental to health. Australian Aboriginal people have a higher rate of cigarette smoking compared with the national average. Thus, we aim to measure the proportion of children admitted to Alice Springs Hospital who are exposed to tobacco smoke at home, to correlate this with prevalence of regular cough and gauge smokers' interest in quitting. Method: A questionnaire was administered verbally to carers of children admitted to Alice Springs Hospital, November 2006 to January 2007. Main outcome measures were presence of a smoker at home and presence of a regular cough. We measured the interest of carers and speculated interest of other smokers in quitting. Eighty-two questionnaires were completed (60% of children admitted during the study period). Eighty-nine per cent of children were Aboriginal. Results: As so few non-Aboriginal children were included in the study, their results were not included in analysis. Sixty-four per cent of children lived with at least one smoker. Seventy per cent of children exposed to smoke at home lived with more than one smoker. Point prevalence of reported regular cough was 33%. Forty-three per cent of children who lived with at least one smoker had regular cough compared with 13% in those who did not (P= 0.035). The rate ratio for regular cough when living with a smoker versus when not living with a smoker was 2.77 (95% confidence interval: 1.06–7.23). Forty-two per cent of the smokers expressed interest in quitting. Conclusion: It is concerning that the majority of hospitalised children were exposed to tobacco smoke at home, while fewer than half of smokers were interested in quitting.

By using a microfluidic electrophoresis platform to perform DNA sequencing, genomic information can be obtained more quickly and affordably than the currently employed capillary array electrophoresis (CAE) instruments. Previous research in our group has shown that physically cross-linked, hydrophobically modified polyacrylamide (HMPAM) matrices separate double-stranded DNA (dsDNA) more effectively than linear polyacrylamide (LPA) solutions. Expanding upon this work, we have synthesized a series of linear polyacrylamide-co-dihexylacrylamide (LPA-co-DHA) block copolymers specifically designed to electrophoretically sequence single-stranded DNA (ssDNA) quickly and efficiently on a microfluidic device. By incorporating very small amounts of N,N-dihexylacrylamide, a hydrophobic monomer, these copolymer solutions achieved up to ~10% increases in average DNA sequencing read length over LPA homopolymer solutions of matched molar mass. Additionally, the inclusion of the small amount of hydrophobe does not significantly increase the polymer solution viscosities, relative to LPA solutions, so that channel loading times between the copolymers and the homopolymers are similar. The resulting polymer solutions are capable of providing enhanced sequencing separations in a short period of time without compromising the ability to rapidly load and unload the matrix from a microfluidic device.

Background and purpose: Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib.

A simple radical-based route to gem-α-dichloroketones, relying on the degenerative addition transfer of (S)-[3,3-dichloro-2-oxopropyl]-O-ethyl dithiocarbonate (xanthate), is described. The adducts can then be converted into Z-enoates by exposure to Et3N in methanol. In the case of certain substrates, it was possible to form skipped dienoic acid and methyl E,E-dienoates.

This article explores the connections between sexual violence, gender inequality, and HIV transmission. Beginning with the premise that HIV/AIDS is a gendered pandemic, the article demonstrates the ways that patterns of HIV transmission are structured by gender and social inequalities. This is due in part to the ways in which women's sexual and reproductive health choices are dominated by socio-cultural expectations and impacted by women's subordinate status in society. Using a country case study from Malawi, Africa, this research demonstrates how the nature and scale of sexual violence impacts both on women's vulnerability to HIV infection and on women's sexual and reproductive health rights. In particular, the article focuses on the conceptualization of sexual violence, the transaction of sex within the local economy and fish industry, and the construction of sex and sexuality as this influences cultural practices and women's vulnerability to HIV transmission. This research finds that Malawian women are situated in a social, legal, and political-economic environment that sustains unequal gender power relations that tolerate the perpetuation of violence against women and leave them more vulnerable to HIV infection and the infringement of their sexual and reproductive health rights.

Objectives: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality. Design: Prospective observational study. Setting: The Cardiovascular Health Study (CHS) in four U.S. communities. Participants: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years. Measurements: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death. Results: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2–12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1–6.0) during the first year after hospitalization and 2.6 (95% CI=2.2–3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1–4.8) and 2.0 (95% CI=1.6–2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function. Conclusion: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.

Objective: To evaluate the effectiveness of hospital admissions for indigenous children with malnutrition in a rural/remote Australian centre. Design: Retrospective review of the medical records. Setting: Rural secondary hospital. Subjects: Remote and rural indigenous children aged less than four years managed for malnutrition in Alice Springs Hospital (ASH). Main outcome measure: The primary outcome measure was weight gain during hospitalisation and posthospitalisation. Secondary outcome measures were yield of investigations, diagnoses made, treatments given, social interventions, readmission rate and nosocomial infection. Results: Median age of the 55 children was 15.1 months. Median weight change was 1.5 g day−1prior to hospitalisation, 36.7 g day−1during and 9 g day−1two months following hospitalisation (P

BACKGROUND: To minimize the bacterial contamination rate in blood collected from donors, a study was designed to evaluate the suitability of a single-use chlorhexidine-alcohol antiseptic for donor arm preparation at all blood collection venues in Australia. STUDY DESIGN AND METHODS: A prospective study of bacterial load on the skin was performed on 616 blood donors’ arms before and after disinfection using a direct swabbing and plating technique. Disinfection was achieved with a swab containing 1 percent chlorhexidine gluconate with 75 percent alcohol, which was applied to the skin in a prescribed method. Feedback from blood donors and staff was obtained using questionnaires. RESULTS: After disinfection, 99 percent of donor arms had bacterial counts of 5 cfu per plate or less, and 99.5 percent had counts of 10 cfu per plate or less, respectively. The mean colony count for all donors after disinfection was 0.39, and the percentage reduction was 99 compared to predisinfection. Sixteen donors (3%) noted transient skin irritation. The majority of staff (64%) preferred not to use the new disinfectant due to the difficulty opening the packaging and an excessive amount of antiseptic solution per pack. CONCLUSION: The bacteriologic study showed that the disinfectant satisfied the requirements of the Australian Red Cross Blood Service for use to prepare blood-donor arms before venesection. An improvement to the packaging was required before it could be acceptable to all staff.

Objective: Electroencephalography (EEG) power and coherence changes may be trait markers for alcoholism providing clues to brain mechanisms of vulnerability. However, it is unclear whether alpha power and coherence differences reflect reversible toxic or withdrawal effects of alcohol. Method: The EEGs of 10 non-abstinent and 16 long-term abstinent alcoholics (7.7 ± 5.8 years) and 25 controls were analyzed. Levels of anxiety and depression were assessed by questionnaire. Results: No statistically significant EEG power differences were observed between groups, although the numerical difference between alcoholics and controls was similar to that previously reported. Bilateral, intrahemispheric, posterior coherences were significantly increased in the alpha and beta frequency bands both in long-term abstinent and non-abstinent alcohol-dependent subjects – particularly when depressiveness was included as a covariate. Conclusion: These results suggest that increased EEG-coherence (cortical synchronization) may serve as endophenotype for alcoholism in conjunction with increased depressiveness and point to a possible involvement of GABAergic and/or glutamatergic neurotransmission.

Older Americans experience chronic disease at rates well above other segments of our society. Rates of health services use are also 2 to 3 times that of younger age groups. The most rapidly growing segments of America's aging population are also its most nutritionally vulnerable-women, minorities, and those 85 years of age and older. The routine incorporation of nutrition screening and intervention into chronic disease management protocols will lower healthcare services usage, decrease healthcare costs, help relieve the burden of human suffering experienced by older Americans with chronic disease, and improve quality of life for our nation's elders.

RANEY® cobalt, which was first prepared in the 1930s, is known to function effectively as a catalyst for certain chemoselective reductions. However, its utility in chemical synthesis does not seem to have been fully appreciated. This first comprehensive survey of the literature on chemical transformations involving RANEY® cobalt attempts to redress matters by, among other things, highlighting the differences between the performance of this system and its much more well-known but usually less selective congener RANEY® nickel. A reliable method for preparing consistently effective RANEY® cobalt is presented together with a protocol that avoids the need to use it with high pressures of dihydrogen. As such, it is hoped more attention will now be accorded to the title reagent that offers considerable promise as a powerful tool for chemical synthesis, particularly in the assembly of polycyclic frameworks through tandem reductive cyclisation processes.

Background: The robust association of alcoholism with reduced P300 event-related potential amplitude has been largely established in severely affected alcoholics and their offspring. Few studies have examined the relationship of increased arousal, anxiety, and P300. In this study, we sought to determine whether P300 group differences could be discerned in well functioning individuals with less severe forms of alcohol use disorders and anxiety disorders. We were particularly interested in looking at the subgroup of alcohol use disorders accompanied by anxiety disorders. This subgroup has previously been found to have diminished α amplitude in the resting EEG. Methods: Male and female community volunteers (99 unrelated index participants and 78 relatives) and 21 unrelated volunteers from an anxiety disorder clinic were interviewed by using the Schedule for Affective Disorders and Schizophrenia, Lifetime version. Blind-rated lifetime psychiatric diagnoses were assigned according to DSM-III-R criteria. Auditory and visual P300 event-related potentials were elicited with an oddball paradigm and were recorded at the midparietal (Pz) site. Results: As expected, auditory P300 amplitudes were significantly reduced in participants with alcohol use disorders and significantly increased in participants with lifetime anxiety disorders. However, more detailed analysis revealed that, in an apparent paradox, auditory P300 amplitudes were lowest in individuals with comorbid alcohol use and anxiety disorders and highest in individuals with anxiety disorders alone. Visual P300 amplitudes followed the same trends but were generally not significant. Conclusions: Even in a sample of largely community-ascertained individuals, auditory P300 amplitude is reduced in alcoholics, particularly those with anxiety disorders, and is highest in nonalcoholics with anxiety disorders.

Ion beam analysis (IBA) on the nanometer scale using the time-of-flight heavy-ion elastic recoil detection analysis technique reveals changes in the elemental composition (depth profiling) of high-temperature nitrided thin silicon oxide (SiO2) layers formed on wafer silicon. An increased uptake of nitrogen with both increased temperature and surprisingly increased thickness of the thin SiO2 layers has been measured. The initial stage of nitridation could be illuminated, indicating the formation of silicon oxynitride subject to nitridation parameters. Previous surface topology investigations with scanning electron microscopy (SEM) revealed concentric annular artificial patterns at the surfaces of specially prepared specimens.

Using a combination of theoretical sequence structure recognition predictions and experimental disulfide bond assignments, a three-dimensional (3D) model of human interleukin-7 (hIL-7) was constructed that predicts atypical surface chemistry in helix D that is important for receptor activation. A 3D model of hIL-7 was built using the X-ray crystal structure of interleukin-4 (IL-4) as a template (Walter MR et al., 1992, J Mol Biol. 224:1075-1085; Walter MR et al., 1992, J Biol Chem 267:20371-20376). Core secondary structures were constructed from sequences of hIL-7 predicted to form helices. The model was constructed by superimposing IL-7 helices onto the IL-4 template and connecting them together in an up-up down-down topology. The model was finished by incorporating the disulfide bond assignments (Cys3, Cys142), (Cys35, Cys130), and (Cys48, Cys93), which were determined by MALDI mass spectroscopy and site-directed mutagenesis (Cosenza L, Sweeney E, Murphy JR, 1997, J Biol Chem 272:32995-33000). Quality analysis of the hIL-7 model identified poor structural features in the carboxyl terminus that, when further studied using hydrophobic moment analysis, detected an atypical structural property in helix D, which contains Cys 130 and Cys142. This analysis demonstrated that helix D had a hydrophobic surface exposed to bulk solvent that accounted for the poor quality of the model, but was suggestive of a region in IL-7 that maybe important for protein interactions. Alanine (Ala) substitution scanning mutagenesis was performed to test if the predicted atypical surface chemistry of helix D in the hIL-7 model is important for receptor activation. This analysis resulted in the construction, purification, and characterization of four hIL-7 variants, hIL-7(K121A), hIL-7(L136A), hIL-7(K140A), and hIL-7(W143A), that displayed reduced or abrogated ability to stimulate a murine IL-7 dependent pre-B cell proliferation. The mutant hIL-7(W143A), which is biologically inactive and displaces [125I]-hIL-7, is the first reported IL-7R system antagonist.

Background: Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. Methods: We evaluated these findings using an independent, similarly established, dataset of 120 subjects. Wc also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. Results: In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 times) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low-amplitude alpha activity that was associated with alcohol use disorders. Conclusions: The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders.

Hurst analysis of EKG data obtained from a population of alcoholic (n = 13) and nonalcoholic (n = 48) subjects was undertaken. Potential subjects (n = 120) were screened using the Schedule for Affective Disorders and Schizophrenia and Structured Clinical Interview for DSM-III instruments. Data from subjects with a diagnosis of current alcohol dependence were analyzed. Subjects with diagnoses such as major depression, bipolar disorder or schizophrenia (Axis I diagnoses), or personality disorders (Axis II diagnoses) were excluded from analysis. Subjects undergoing testing were free of alcohol and illicit drugs. Alcoholic subjects had no clinical evidence of alcohol withdrawal symptoms at the time of testing. EKG data were obtained with eyes open or with eyes closed. Approximately 3.5 min of data were obtained for each condition. Alcoholic subjects had less complex heart rate dynamics as evidenced by higher values of H = 0.18 +/- 0.05 (mean +/- SEM), compared with healthy comparison subjects with H = 0.09 +/- 0.02, p < 0.014 for the eyes closed condition, and H = 0.17 +/- 0.05 (mean +/- SEM) compared with healthy comparison subjects with H = 0.07 +/- 0.02,p < 0.011 for the eyes open condition. A gender effect was seen, with female subjects showing evidence of more complex heart rate dynamics than male subjects.

A new method is presented for identifying distantly related homologous proteins that are unrecognizable by conventional sequence comparison methods. The method combines information about functionally conserved sequence patterns with information about structure context. This information is encoded in stochastic discrete state-space models (DSMs) that comprise a new family of hidden Markov models. The new models are called sequence-pattern-embedded DSMs (pDSMs). This method can identify distantly related protein family members with a high sensitivity and specificity. The method is illustrated with trypsin-like serine proteases and globins. The strategy for building pDSMs is presented. The method has been validated using carefully constructed positive and negative control sets. In addition to the ability to recognize remote homologs, pDSM sequence analysis predicts secondary structures with higher sensitivity, specificity, and Q3 accuracy than DSM analysis, which omits information about conserved sequence patterns. The identification of trypsin-like serine proteases in new genomes is discussed.

A history of the goals, activities, and accomplishments of the Nutrition Screening Initiative (NSI) is provided. A commentary on the development and intended use of the NSI's self-assessment and screening tools is given to facilitate selection of feeding devices for older Americans who need nutrition care. Additional questionnaires and interventions designed to address the needs identified through the NSI's standardized, interdisciplinary approach to the assessment of nutritional risk are described and their use encouraged. Legislative and public policy advocacy is summarized. A systemic approach to the assessment and maintenance of optimal nutritional health in the older population will have a profound effect on health care delivery systems.

We thank the Australian Research Council and the Institute of Advanced Studies for generous financial support.

As human knowledge and civilisation progress, these characteristic differences [in human behaviour] tend to develop and multiply themselves, rather than decrease. Character grows more many sided. Two well-educated Englishmen are far better distinguished from each other than two common labourers, and these are better distinguished than two Australian aborigines. [W. Stanley Jevons 1887, 734] I. INTRODUCTION Scholars have devoted much attention in recent years to explaining the differences between the basic analytical frameworks of classical political economy and the marginalist supply and demand theories published by William Stanley Jevons and Leon Walras in the 1860s and 1870s. While disagreeing over the precise form of the differences, historians of economics commonly describe the "marginalist revolution" by three interrelated aspects of its analytical domain. As summarized by Winch [1972], these aspects are (1) the type of problems considered to be within the domain of economic science; (2) the criteria used to designate the domain boundary so as to distinguish between "economic science" and other types of analysis; and (3) the conceptualization of economic actors within the domain. More specifically, Winch argues that marginalism is distinguished by its "recognizing scarcity of given means in relation to alternative uses as the economic problem" and explaining this in terms of the "universal application of the laws of human choice" [1972, 328, Winch's italics, 335]. With activity in the domain of economic science "explicitly including both material and immaterial goods and services, moral and immoral," its boundary was set by drawing a clear distinction between "pure and applied science" which corresponded to the distinction between positive and normative propositions. Finally, the depiction of economic actors entailed a "thorough going individualism ... which placed the rational maximizer at the centre of things." In keeping with this account, Cohen and Cohen [1983, 195-197] have argued that, while the concept of social class was a "fundamental aspect" of classical political economy, it was "irrelevant" in marginalism because "individuals form the basic unit of analysis, and individual demand is the driving force of the system. These aspects can be seen most clearly in Jevons's work."(1) I will argue here that this characterization of the economic domain in Jevons's marginalism is misleading and that it effaces a number of important differences between the ideas propounded in his Theory of Political Economy (hereafter Political Economy) and later versions of supply and demand theory. Using the discussion of reduced working hours in Political Economy to illustrate the analysis, I will show that the theoretical object of Political Economy cannot be reduced to an analysis of "rational behavior" per se and that Jevons did not rely on a distinction between positive and normative propositions. Indeed, he argued that the domain of economic science provided the means to advocate or reject particular government policies. Moreover, although there is an important analytical difference between the social individuals of the classical framework and the abstract individuals of marginalism, references to Jevons's individualism do not explain the significance of the discussion of class and race behavior which pervades his work.(2) The paper is presented in four sections. The first discusses how Jevons specified the domain of "scientific" political economy using a particular Utilitarian theory of ethics. This enabled him to make a distinction between policy questions which lay within the province of economic science and those which did not because they raised questions of ethics and duty. One policy question which fell outside the domain was legislation to reduce working hours, and the next two sections show why that was the case. Section III considers the "scientific" analysis of work hours in Political Economy where Jevons explained different work patterns in terms of class and race behavior. …

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“In the development of the mental sciences exegesis has frequently played an important part. A change of doctrine has been justified, or supported, or commended for general acceptance, by the interpretation of an authoritative text.” W. J. Ashley (1895, p. 474). “We must … try to avoid an outlook narrowly constrained by the marginalist principles of 1871.” Samuel Hollander (1973, p. 138).

Alfred Marshall's introduction of the ‘Giffen Good’ case appears puzzling, if only because it was not discussed by Robert Giffen. This article suggests that the analytical framework which Marshall used to discuss the case owed a good deal to the work of W.S. Jevons. The precise argument, however, was introduced as a rhetorical device to defend the notion of consumer surplus (against J.S. Nicholson) and to criticize the advocacy of tariff reform (by W.A.S. Hewins).