Form switching during human locomotion: traversing wedges in a single step.
We examined the neural control strategies used to accommodate discrete alterations in walking surface inclination. Normal subjects were tested walking on a level surface and on different wedges (10 degrees, 15 degrees, 20 degrees, and 30 degrees ) presented in the context of level walking. On a given trial, a subject walked on a level surface in approach to a wedge, took a single step on the wedge, and continued walking on an elevated level surface beyond the wedge. As wedge inclination increased, subjects linearly increased peak joint angles. Changes in timing of peak joint angles and electromyograms were not linear. Subjects used two distinct temporal strategies, or forms, to traverse the wedges. One form was used for walking on a level surface and on the 10 degrees wedge, another form for walking on the 20 degrees and 30 degrees wedges. In the level/10 degrees form, peak hip flexion occurred well before heel strike (HS) and peak dorsiflexion occurred in late stance. In the 20 degrees /30 degrees form, peak hip flexion was delayed by 12% of the stride cycle and peak dorsiflexion was reached 12% earlier. For the level/10 degrees form, onsets of the rectus femoris, gluteus maximus, and vastus lateralis muscles were well before HS and offset of the anterior tibialis was at HS. For the 20 degrees /30 degrees form, onsets of the rectus femoris, gluteus maximus, and vastus lateralis and offset of the anterior tibialis were all delayed by 12% of the stride cycle. Muscles shifted as a group, rather than individually, between the forms. Subjects traversing a 15 degrees wedge switched back and forth between the two forms in consecutive trials, suggesting the presence of a transition zone. Differences between the forms can be explained by the differing biomechanical constraints imposed by the wedges. Steeper wedges necessitate changes in limb orientation to accommodate the surface, altering limb orientation with respect to gravity and making it necessary to pull the body forward over the foot. The use of different forms of behavior is a common theme in neural control and represents an efficient means of coordinating and adapting movement to meet changing environmental demands. The forms of locomotion reported here are likely used on a regular basis in real-world settings.


Application of scan statistics to detect suicide clusters in Australia.
Suicide clustering occurs when multiple suicide incidents take place in a small area or/and within a short period of time. In spite of the multi-national research attention and particular efforts in preparing guidelines for tackling suicide clusters, the broader picture of epidemiology of suicide clustering remains unclear. This study aimed to develop techniques in using scan statistics to detect clusters, with the detection of suicide clusters in Australia as example. Scan statistics was applied to detect clusters among suicides occurring between 2004 and 2008. Manipulation of parameter settings and change of area for scan statistics were performed to remedy shortcomings in existing methods. In total, 243 suicides out of 10,176 (2.4%) were identified as belonging to 15 suicide clusters. These clusters were mainly located in the Northern Territory, the northern part of Western Australia, and the northern part of Queensland. Among the 15 clusters, 4 (26.7%) were detected by both national and state cluster detections, 8 (53.3%) were only detected by the state cluster detection, and 3 (20%) were only detected by the national cluster detection. These findings illustrate that the majority of spatial-temporal clusters of suicide were located in the inland northern areas, with socio-economic deprivation and higher proportions of indigenous people. Discrepancies between national and state/territory cluster detection by scan statistics were due to the contrast of the underlying suicide rates across states/territories. Performing both small-area and large-area analyses, and applying multiple parameter settings may yield the maximum benefits for exploring clusters.


ECMO in evolution: the impact of changing patient demographics and alternative therapies on ECMO.
The incidence of neonatal extracorporeal membrane oxygenation (ECMO) is decreasing nationally. This decrease is presumed to be a result of the emergence of alternative technologies such as high-frequency oscillatory ventilation (HFOV), nitric oxide (NO), and surfactant therapy as well as others. The purposes of the present report were to determine just how rapidly the demographics of ECMO are changing and to determine the impact of competing technologies on ECMO use. The authors reviewed their entire ECMO experience of 455 cases (370 neonatal, 38 pediatric, and 47 cardiac). The neonatal cases also were separated into diagnostic groups: MAS (meconium aspiration syndrome), PPHN (persistent pulmonary hypertension of the newborn), RDS (respiratory distress syndrome), and sepsis. To allow statistical comparison, the patients were divided into four chronological groups, of equal 3-year duration, spanning the 12 years that ECMO has been available. The results of the analysis demonstrated four principle findings. (1) The total number of patients receiving ECMO per year was declining (P = .0001). This decline was attributable to a reduction in the total number of neonatal patients, with the exception of cases of congenital diaphragmatic hernia. (2) The complexity of each ECMO run was increasing, as evidenced by substantial increases in mean ECMO duration per patient and an increase in the incidence of patient complications on ECMO (P = .0001). (3) There has been a significant decrease in the overall survival rate for patients treated with ECMO (P = .0001). (4) The ECMO population mix has shifted away from straightforward neonatal cases and toward the more complex pediatric and cardiac cases. This demographic shift has occurred as a result of improvements in pre-ECMO management of neonatal patients, and is primarily responsible for the findings noted above. However, there also has been a worsening of condition severity within each diagnostic group, which also is partly responsible for the changes noted. If these trends continue, pediatric, cardiac, and CDH patients will likely account for the majority of ECMO patients. Consequently, existing ECMO centers must be prepared to adapt to the changing demographics by evolving programs that support pediatric, cardiac, and adult patients, in addition to neonates. Furthermore, the complexity associated with transporting these unstable older patients and the likelihood that the number of active ECMO centers will decline may require remaining ECMO centers to develop long-distance ECMO transport capabilities.


U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact.
Our objective was to obtain national data of the estimated prevalence, sociodemographic relationships, and health impact of persons with functional gastrointestinal disorders. We surveyed a stratified probability random sample of U.S. householders selected from a data base of a national market firm (National Family Opinion, Inc.). Questions were asked about bowel symptoms, sociodemographic associations, work absenteeism, and physician visits. The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region, age of householder, population density, household income, and household size. Of 8250 mailings, 5430 were returned suitable for analysis (66% response). The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic (Rome) criteria. Additional variables studied included: demographic status, work absenteeism, health care use, employment status, family income, geographic area of residence, population density, and number of persons in household. For this sample, 69% reported having at least one of 20 functional gastrointestinal syndromes in the previous three months. The symptoms were attributed to four major anatomic regions: esophageal (42%), gastroduodenal (26%), bowel (44%), and anorectal (26%), with considerable overlap. Females reported greater frequencies of globus, functional dysphagia, irritable bowel syndrome, functional constipation, functional abdominal pain, functional biliary pain and dyschezia; males reported greater frequencies of aerophagia and functional bloating. Symptom reporting, except for incontinence, declines with age, and low income is associated with greater symptom reporting. The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder. Furthermore, the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain, biliary pain, functional dyspepsia and IBS. Preliminary information on the prevalence, socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders.


The provision of chiropractic, physiotherapy and osteopathic services within the Australian private health-care system: a report of recent trends.
Chiropractors, physiotherapists, and osteopaths receive training in the diagnosis and management of musculoskeletal conditions. As a result there is considerable overlap in the types of conditions that are encountered clinically by these practitioners. In Australia, the majority of benefits paid for these services come from the private sector. The purpose of this article is to quantify and describe the development in service utilization and the cost of benefits paid to users of these healthcare services by private health insurers. An exploration of the factors that may have influenced the observed trends is also presented. A review of data from the Australian Bureau of Statistics, Australian Health Practitioner Regulation Agency, and the Australian Government Private Health Insurance Administration Council was conducted. An analysis of chiropractic, physiotherapy and osteopathic service utilisation and cost of service utilisation trend was performed along with the level of benefits and services over time. In 2012, the number of physiotherapists working in the private sector was 2.9 times larger than that of chiropractic, and 7.8 times that of the osteopathic profession. The total number of services provided by chiropractors, physiotherapists, and osteopaths increased steadily over the past 15 years. For the majority of this period, chiropractors provided more services than the other two professions. The average number of services provided by chiropractors was approximately two and a half times that of physiotherapists and four and a half times that of osteopaths. This study highlights a clear disparity in the average number of services provided by chiropractors, physiotherapists, and osteopaths in the private sector in Australia over the last 15 years. Further research is required to explain these observed differences and to determine whether a similar trend exists in patients who do not have private health insurance cover.


High rates of Rickettsia parkeri infection in Gulf Coast ticks (Amblyomma maculatum) and identification of "Candidatus Rickettsia andeanae" from Fairfax County, Virginia.
The Gulf Coast tick, Amblyomma maculatum, is a vector of Rickettsia parkeri, a recently identified human pathogen that causes a disease with clinical symptoms that resemble a mild form of Rocky Mountain spotted fever. Because the prevalence of R. parkeri infection in geographically distinct populations of A. maculatum is not fully understood, A. maculatum specimens collected as part of a tick and pathogen surveillance system in Fairfax County, Virginia, were screened to determine pathogen infection rates. Overall, R. parkeri was found in 41.4% of the A. maculatum that were screened. Additionally, the novel spotted fever group Rickettsia sp., tentatively named "Candidatus Rickettsia andeanae," was observed for the first time in Virginia.


Infection of the central nervous system produced by R1 vesicular stomatitis virus.
Previous studies of vesicular stomatitis virus infection of the central nervous system in mice have demonstrated that both temperature-sensitive mutants and defective interfering particles produce alterations from wild type disease. To examine further the role of the biologic properties of the virus, we studied the disease produced by R1-vesicular stomatitis virus, a temperature-insensitive revertant derived from the temperature-sensitive T1026 mutant. Whereas wild type produced acute encephalitis and death in 2 to 3 days in BALB/c mice, R1 produced, in contrast, a paralytic disease 5 to 6 days postinoculation and death on days 6 to 7. R1 infection is productive, although with altered kinetics of growth. No alterations of the biologic properties of the virus following intracerebral passage could be detected. The morphologic features showed a striking localization of viral replication and damage to the anterior horns of the spinal cord with sparing of the ependymal cells, unlike the situation in wild type infection. At the time of clinical onset of R1 disease, the morphologic appearances were degenerative in nature. These features correlate with the clinical localization and development of disease. In addition, morphologic evidence for trans-synaptic spread of R1 and wild type has been found. Although the delayed and altered central nervous system disease resembles aspects of delayed disease produced in other situations, it seems clear that the mechanisms operative here are unlike those previously described and may be related to a unique genomic defect in R1 or its interaction with host cell factors.


Predictors of effortful control among children of alcoholic and nonalcoholic fathers.
The purpose of this study was (1) to examine the association between fathers' alcoholism and children's effortful control and (2) to examine the role of parental warmth and toddler temperament as mediators or moderators of this relationship. Families were recruited through New York State birth records when their infant was age 12 months. The final sample consisted of 226 families (116 boys) constituting two major groups: a nonalcoholic group consisting of parents with no or few current alcohol problems (n = 102) and a father alcoholic group (n = 124). Families were assessed when their child was ages 12, 18, 24 and 36 months. Results indicate that boys of alcoholic fathers exhibit lower overall levels of effortful control than boys of nonalcoholic fathers. For boys, fathers' warmth over the second year of life mediated the association between fathers' alcoholism and effortful control. Maternal warmth was a unique predictor of effortful control for boys. For girls, fathers' alcoholism was associated with lower paternal warmth, which was in turn a significant predictor of effortful control. Child activity level and negative affect were associated with effortful control for boys but did not account for significant variance when entered in regression models with fathers' alcoholism and parenting variables. Sons of alcoholic fathers are at an increased risk of problems in self-regulation when they are ages 2 to 3 years. Paternal warmth mediates the association between fathers' alcoholism and self-regulation for both boys and girls, although the nature of mediation may vary by child gender.


Movement Rate Is Encoded and Influenced by Widespread, Coherent Activity of Cerebellar Molecular Layer Interneurons.
Inhibition from molecular layer interneurons (MLIs) is thought to play an important role in cerebellar function by sharpening the precision of Purkinje cell spike output. Yet the coding features of MLIs during behavior are poorly understood. To study MLI activity, we used in vivo Ca2+ imaging in head-fixed mice during the performance of a rhythmic motor behavior, licking during water consumption. MLIs were robustly active during lick-related movement across a lobule-specific region of the cerebellum showing high temporal correspondence within their population. Average MLI Ca2+ activity strongly correlated with movement rate but not to the intentional, or unexpected, adjustment of lick position or to sensory feedback that varied with task condition. Chemogenetic suppression of MLI output reduced lick rate and altered tongue movements, indicating that activity of these interneurons not only encodes temporal aspects of movement kinematics but also influences motor outcome pointing to an integral role in online control of rhythmic behavior.SIGNIFICANCE STATEMENT The cerebellum helps fine-tune coordinated motor actions via signaling from projection neurons called Purkinje cells. Molecular layer interneurons (MLIs) provide powerful inhibition onto Purkinje cells, but little is understood about how this inhibitory circuit is engaged during behavior or what type of information is transmitted through these neurons. Our work establishes that MLIs in the lateral cerebellum are broadly activated during movement with calcium activity corresponding to movement rate. We also show that suppression of MLI output slows and disorganizes the precise movement pattern. Therefore, MLIs are an important circuit element in the cerebellum allowing for accurate motor control.


"Culture of drinking" and individual problems with alcohol use.
Binge drinking is a substantial and growing health problem. Community norms about drinking and drunkenness may influence individual drinking problems. Using data from the New York Social Environment Study (n = 4,000) conducted in 2005, the authors examined the relation between aspects of the neighborhood drinking culture and individual alcohol use. They applied methods to address social stratification and social selection, both of which are challenges to interpreting neighborhood research. In adjusted models, permissive neighborhood drinking norms were associated with moderate drinking (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.05, 1.55) but not binge drinking; however, social network and individual drinking norms accounted for this association. By contrast, permissive neighborhood drunkenness norms were associated with more moderate drinking (OR = 1.20, 95% CI: 1.03, 1.39) and binge drinking (OR = 1.92, 95% CI: 1.44, 2.56); the binge drinking association remained after adjustment for social network and individual drunkenness norms (OR = 1.58, 95% CI: 1.20, 2.08). Drunkenness norms were more strongly associated with binge drinking for women than for men (p(interaction) = 0.006). Propensity distributions and adjustment for drinking history suggested that social stratification and social selection, respectively, were not plausible explanations for the observed results. Analyses that consider social and structural factors that shape harmful drinking may inform efforts targeting the problematic aspects of alcohol consumption.


Impact of hospital policies on breastfeeding outcomes.
The objective of this study was to explore the association between the Ten Steps of the Baby Friendly Hospital Initiative (BFHI) of the World Health Organization (Geneva, Switzerland) and breastfeeding at 2 days and 2 weeks. A 65-question institutional survey assessing compliance with the Ten Steps was used to determine an overall breastfeeding Support Score for each of Oregon's 57 birthing hospitals. Hospital breastfeeding outcomes were obtained from the newborn metabolic screening forms. Hospitals' overall breastfeeding Support Scores ranged from 49.4 to 98.2 out of a possible total score of 100. Hospital compliance with individual Steps ranged from 5.3% for Step 2 (staff training) to 93% for Step 4 (helping with breastfeeding initiation) and Step 8 (encouraging feeding on demand). After controlling for institutional differences (by multivariate linear regression) we found that increases in overall hospital breastfeeding Support Scores were associated with increases in breastfeeding percentage at 2 days (p = 0.021) and at 2 weeks postpartum (p = 0.011). In analyzing each Step individually, however, only the presence of a written hospital policy was independently associated with breastfeeding percent (p = 0.028). This institutional-level evaluation corroborates previous findings demonstrating that increased implementation of the Ten Steps is associated with increased breastfeeding. Further, it suggests that hospitals with comprehensive breastfeeding policies are likely to have better breastfeeding support services and better breastfeeding outcomes. Hospitals may consider using these results to prioritize breastfeeding support services through development of hospital breastfeeding policies and to utilize institutional surveys as a component of breastfeeding quality improvement initiatives.


12 Tips for taking a Student Led Medical Education Program from Concept to Curriculum.
This article was migrated. The article was marked as recommended. The choice of a future career specialty has always been a stressful decision for medical students. To mitigate this stress and assist students in making more informed career decisions we developed the Pre-clerkship Residency Exploration Program (PREP), a two-week summer elective program that provides students with the opportunity to gain exposure to specialities that traditionally do not receive a lot of attention in medical school. To initiate this student led program we faced many obstacles, suffered many failures, learned a tremendous amount and eventually found success. In this article, we offer 12 tips on how to create a medical education program that is sustainable, effective and receives strong buy-in from faculty and administration. Our tips come from the perspective of students starting their own program but are translatable to anyone interested in taking an innovative idea and seeing it through to fruition.


Progress in clinical and basic research of epilepsy surgery in China.
This article outlines some current status of clinical application of epilepsy surgery and the achievements already obtained in this field in China. The rapid development of modern science and technology has furthered the understanding and definition of the scope where surgical operations are applicable, and facilitated the continuous improvement in the diagnosis and treatment approaches. Also concerned in this article is the current status of the epilepsy-related basic research and the latest progress, with the existing problems identified and future development potential of epilepsy surgery weighted.


Barriers to accessing and using health insurance cards among methadone maintenance treatment patients in northern Vietnam.
Methadone maintenance treatment (MMT) patients face unique costs associated with their healthcare expenditures. As such, it is important that these patients have access to health insurance (HI) to help them pay for both routine and unforeseen health services. In this study, we explored factors related to health insurance enrollment and utilization among MMT patients, to move Vietnam closer to universal coverage among this patient population. A cross-sectional study was conducted with 1003 patients enrolled in MMT in five clinics in Hanoi and Nam Dinh provinces. Patients were asked a range of questions about their health, health expenditures, and health insurance access and utilization. We used multivariate logistic regressions to determine factors associated with health insurance access among participants. The majority of participants (nearly 80%) were not currently enrolled in health insurance at the time of the study. Participants from rural regions were significantly more likely than urban participants to report difficulty using HI. Family members of participants from rural regions were more likely to have overall poor service quality through health insurance compared with family members of participants from urban regions. Overall, 37% of participants endorsed a lack of information about HI, nearly 22% of participants reported difficulty accessing HI, 22% reported difficulty using HI, and more than 20% stated they had trouble paying for HI. Older, more highly educated, and employed participants were more likely to have an easier time accessing HI than their younger, less well educated, and unemployed counterparts. HIV-positive participants were more likely to have sufficient information about health insurance options. Our study highlights the dearth of health insurance utilization among MMT patients in northern Vietnam. It also sheds light on factors associated with increased access to and utilization of health insurance among this underserved population. These results can help improve health insurance enrollment among MMT patients, a population that is at increased need of financial assistance in accessing health services.


Active compounds and derivatives of camellia sinensis responding to erosive attacks on dentin.
This research explored the potential of Camellia sinensis-derived teas and active compounds to be used as treatments to prevent dentin wear. Human root dentin slabs were randomly assigned to 5 groups (n = 10) as follows: distilled water (DW, control), epigallocatechin-3-gallate (EGCG), theaflavin gallate derivatives (TF), commercial green tea (GT), and commercial black tea (BT). The samples were submitted to a pellicle formation and an erosive cycling model (5x/day, demineralization using 0.01 M hydrochloric acid/60 s) followed by remineralization (human stimulated saliva/60 min) for three days. The samples were treated for 5 min using the test group solutions between the erosive cycles. Dentin changes were assessed with profilometry analysis and FT-Raman spectroscopy. The data regarding wear were analyzed by ANOVA followed by Tukey's test (p < 0.05). EGCG, TF derivatives, and both regular teas significantly suppressed erosive dentin loss (38-47%, p < 0.05). No obvious changes in the Raman spectra were detected in the specimens; however, the DW group had a minor relationship of 2880/2940 cm-1. The phenolic contents in both green and black tea and the important catechins appear to have protective effects on dentin loss.


Etiologies and molecular mechanisms of communication disorders.
Quantitative behavioral genetic studies have made it clear that communication disorders such as reading disability, language impairment, and autism spectrum disorders follow some basic principles: (1) complex disorders have complex causes, in which each clinical disorder is influenced by a number of separate genes; and (2) at least some behaviorally related disorders are influenced by the same genes. Recent advances in molecular and statistical methods have confirmed these principles and are now leading to an understanding of the genes that may be involved in these disorders and how their disruption may affect the development of the brain. The prospect is that the genes involved in these disorders will define a network of interacting neurologic functions and that perturbations of different elements of this network will produce susceptibilities for different disorders. Such knowledge would clarify the underlying deficits in these disorders and could lead to revised diagnostic conceptions. However, these goals are still in the future. Identifying the individual genes in such a network is painstaking, and there have been seemingly contradictory studies along the way. Improvements in study design and additional functional analysis of genes are gradually clarifying many of these issues. When combined with careful phenotypic studies, molecular genetic studies have the potential to refine the clinical definitions of communication disorders and influence their remediation.


Transmission of hepatitis C virus by transfusion in Orebro County, Sweden, 1990-1992.
A retrospective study of hepatitis C virus (HCV) transmission by transfusion was conducted in Orebro county. Out of the 7,900 active, registered blood donors, 21 repeatedly anti-HCV reactive (RIVA 2 positive or indeterminate) donors were diagnosed. Their 84 recipients from January 1990 through June 1992 were identified and 41 (49%) were alive in December 1992. A total of 13 anti-HCV reactive (RIBA 2 positive or indeterminate) were diagnosed in 39 investigated recipients. Of these 11 were previously undiagnosed, and seven were HCV RNA-positive. In the donor population 1.03% were anti-HCV-positive by ELISA, but only 0.09% were RIBA and HCV RNA-positive. In 1990, 0.06% of the blood components came from the HCV RNA-positive donors, and none during the first 6 months of 1992. In order to identify transfusion-transmitted HCV infections that took place before the introduction of tests for anti-HCV antibodies, patients with a history of transfusion and symptoms and signs of liver dysfunction or damage should be thoroughly tested.


General Practitioner Attendance in Proximity to HPV Vaccination: A Nationwide, Register-Based, Matched Case-Control Study.
This study aimed to describe and compare general practitioner (GP) attendance patterns in the years surrounding HPV-vaccination among cases suspected to experience adverse events and their matched controls in order to determine if a potential larger change in GP attendance among cases was observed in temporal relation to vaccination. Register-based, matched case-control study. Cases were defined as women referred to specialized hospital settings (HPV-centers) for suspected adverse event between June 1st 2015 and December 31st 2015 (n=1458). Information on referral was obtained from the HPV-centers directly. Each case was matched with five controls on age at vaccination, region, time of first vaccine registration and total number of doses, resulting in a total study population of 8670 girls and women. Negative binomial regression analyses were used (i) to estimate mean yearly GP contacts among cases and controls, and (ii) to further investigate the relative difference in change in GP attendance following vaccination between cases and controls. Overall, cases displayed higher GP attendance than controls from five years before vaccination up until five years after. Compared to controls, cases increased their GP attendance more in the years following HPV vaccination, corresponding to a 40% increase in the incidence rate ratios (IRR) from before to after vaccination (ratio-IRR = 1.40 [1.36; 1.44]). The change occurred in close proximity to vaccination, and the pattern was the same independently of the year of vaccination. However, for the later vaccination years cases displayed an additional increase in their GP attendance around time of extensive media attention. Girls and women being referred for suspected adverse events after HPV-vaccination changed their GP attendance pattern in close proximity to their first HPV-vaccination and not solely in temporal linkage to the onset of public debate.


Development and characterization of monoclonal antibody to T-antigen: (gal beta1-3GalNAc-alpha-O).
The saccharide antigen, Gal beta1-3GalNAc or T antigen, is of biologic importance in many systems. It is a tumor-associated carbohydrate antigen, a temporally expressed antigen in germinal center B cells and cortical T cells, a parasite-associated antigen, a spermatozoa vitality marker and an antigen on aged red blood cells. It may play a role in normal cellular adhesion and in tumor cell metastasis. Well characterized monoclonal antibodies (MAb) to Gal beta1-3GalNAc will be useful for further studies in these areas. We developed an IgG3 MAb to Gal beta1-3GalNAc by immunizing the mice with a synthetic Gal beta1-3GalNAc-BSA conjugate. The MAb was analyzed using inhibition enzyme immunoassays with related synthetically prepared sugars to determine the restrictions involved in the antibody binding. Use of synthetic sugars as competitors enabled us to delineate the epitope restrictions on the binding activity of this monoclonal and will enable use of this MAb in studies concerning the biologic importance of this disaccharide.


Seasonality of Leaf and Fig Production in Ficus squamosa, a Fig Tree with Seeds Dispersed by Water.
The phenology of plants reflects selection generated by seasonal climatic factors and interactions with other plants and animals, within constraints imposed by their phylogenetic history. Fig trees (Ficus) need to produce figs year-round to support their short-lived fig wasp pollinators, but this requirement is partially de-coupled in dioecious species, where female trees only develop seeds, not pollinator offspring. This allows female trees to concentrate seed production at more favorable times of the year. Ficus squamosa is a riparian species whose dispersal is mainly by water, rather than animals. Seeds can float and travel in long distances. We recorded the leaf and reproductive phenology of 174 individuals for three years in Chiang Mai, Northern Thailand. New leaves were produced throughout the year. Fig production occurred year-round, but with large seasonal variations that correlated with temperature and rainfall. Female and male trees initiated maximal fig crops at different times, with production in female trees confined mainly to the rainy season and male figs concentrating fig production in the preceding months, but also often bearing figs continually. Ficus squamosa concentrates seed production by female plants at times when water levels are high, favouring dispersal by water, and asynchronous flowering within male trees allow fig wasps to cycle there, providing them with potential benefits by maintaining pollinators for times when female figs become available to pollinate.


Point prevalence of tuberculosis among central Americans sheltered in Houston.
A study to determine the point prevalence of tuberculosis, as defined by a positive tuberculin skin test, was conducted among the inhabitants of a Central American shelter. The point prevalence was found to be 50% (17/34). This high point prevalence demonstrates the need to test Hispanics who have recently arrived in the United States for tuberculosis. The difficulty in completing evaluations of those with positive skin tests makes tuberculin skin testing ineffective in controlling tuberculosis in this population and setting. To improve control, local, state, and federal health agencies will need to coordinate their efforts and increase the accessibility of health care to populations at high risk.


Global disease burden of pathogens in animal source foods, 2010.
Animal source foods (ASF) such as dairy, eggs, fish and meat are an important source of high-quality nutrients. Lack of ASF in diets can result in developmental disorders including stunting, anemia, poor cognitive and motor development. ASF are more effective in preventing stunting than other foods and promoting ASF consumption in low- and middle-income countries could help improve health, particularly among pregnant women and young children. Production and consumption of ASF are, however, also associated with potential food safety risks. Strengthening of food control systems, informed by quantitative assessments of the disease burden associated with ASF is necessary to meet global nutrition goals. We present the human disease burden associated with 13 pathogens (bacteria and parasites) in ASF, based on an analysis of global burden of foodborne disease (FBD) estimates of the WHO Foodborne Disease Burden Epidemiology Reference Group (FERG). The FBD burden of these pathogens was combined with estimates of the proportion of disease transmitted by eight main groups of ASF. Uncertainty in all estimates was accounted for by Monte Carlo simulation. In 2010, the global burden of ASF was 168 (95% uncertainty interval (UI 137-219) Disability Adjusted Life Years (DALYs) per 100,000 population, which is approximately 35% of the estimated total burden of FBD. Main pathogens contributing to this burden included non-typhoidal Salmonella enterica, Taenia solium, and Campylobacter spp. The proportion of FBD burden associated with ASF varied considerably between subregions and between countries within subregions. Likewise, the contribution of different pathogens and ASF groups varied strongly between subregions. Pathogens with a localized distribution included T. solium and fishborne trematodes. Pathogens with a global distribution included non-typhoidal S. enterica, Campylobacter spp., Toxoplasma gondii, and Mycobacterium bovis. Control methods exist for many hazards associated with ASF, and their implementation is linked to economic development and effective food safety systems.


Somatostatin-receptor-targeted alpha-emitting 213Bi is therapeutically more effective than beta(-)-emitting 177Lu in human pancreatic adenocarcinoma cells.
Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA(0)-Tyr(3)]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) beta(-)-emitters have shown overall response rates in the range of 15-33%. In order to improve outcomes, we sought to compare the therapeutic effectiveness of sstr-targeted high-LET alpha-emitting (213)Bi to that of low-LET beta(-)-emitting (177)Lu by determining relative biological effectiveness (RBE) using the external gamma-beam of (137)Cs as reference radiation. Sstr-expressing human pancreatic adenocarcinoma Capan-2 cells and A549 control cells were used for this study. The effects of different radiation doses of (213)Bi and (177)Lu labeled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and sstr-targeted DOTATOC were investigated with a clonogenic cell survival assay. Apoptosis was measured using the Cell Death Detection ELISA(PLUS) 10x kit. Using equimolar DOTATOC treatment with concurrent irradiation with a (137)Cs source as reference radiation, the calculated RBE of [(213)Bi]DOTATOC was 3.4, as compared to 1.0 for [(177)Lu]DOTATOC. As measured in terms of absorbance units, [(213)Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [(177)Lu]DOTATOC at the final treatment time of 96 h (P<.001) in sstr-expressing Capan-2 cells. In conclusion, at the same absorbed dose, [(213)Bi]DOTATOC is therapeutically more effective in decreasing survival than is [(177)Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE.


Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in young conventional calves.
Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe. Commercial vaccines against this virus needs improvement of efficacy, especially in calves with BRSV-specific maternally derived antibodies (MDA). We previously reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine, induced strong clinical and virological protection in calves with MDA, immunized at 7-15 weeks of age. The aim of the present study was to characterize the immune responses, as well as to investigate the efficacy and safety in younger animals, representing the target population for vaccination. Four groups of five 3-8 week old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii) BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection. The cellular and humoral responses were monitored as well as the clinical signs, the viral excretion and the pathology following challenge. Despite presence of MDA at the time of the immunization, only a minimum of clinical signs were observed in the BRSV-ISCOM group after challenge. In contrast, in all control groups, clinical signs of disease were observed in most of the animals (respiratory rates up to 76min(-1) and rectal temperatures up to 41°C). The clinical protection was associated to a highly significant reduction of virus replication in the upper and lower respiratory tract of calves, rapid systemic and local antibody responses and T helper cell responses dominated by IFNγ production. Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. The protective immunological responses to BRSV proteins and the ability to overcome the inhibiting effect of MDA were dependent on ISCOM borne antigen presentation.


Effect of Efalizumab on neutrophil and monocyte functions in patients with psoriasis.
We evaluated the effect of efalizumab on neutrophil and monocyte functions. The in vitro pre-incubation with efalizumab concentrations similar to those reached during in vivo therapy almost completely saturated CD11a binding sites without affecting the membrane expression of CD11b, CD128a or CD128b. There was a significant reduction in the chemotactic activity of the pre-treated cells toward three different chemo-attractants, whereas their phagocytic capacity and production of oxygen radicals remained unchanged. One month after the administration of efalizumab to five patients with psoriasis (T1) circulating neutrophil counts increased by 34% from pre-therapy (T0) with no change in the number of monocytes. In the same patients the CD11a binding sites on phagocytes were >90% saturated, and there was also a significant down-modulation on neutrophils (44% of T0) and monocytes (63% of T0). In line with in vitro results, efalizumab treatment caused a significant deficiency in the chemotactic properties of neutrophils and monocytes, but no changes in phagocytosis, oxidative burst, production of pro-inflammatory cytokines or the membrane expression of CD11b, CD128a and CD128b. Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis.


Comparison of chewing cycles in 2-, 3-, 4-, and 5-year-old normal children.
Chewing movements of normal 2-, 3-, and 4-year-old children were measured. Chewing movements of 2- and 3-year-olds were compared with those of 4- and 5-year-olds. Measures were taken on 56 children: 17 were 2 years old (8 female, 9 male); 19 were 3 years old (10 female, 9 male); and 20 were 4 years old (10 female and 10 male). Data of twenty 5-year-olds (10 males, 10 females) were taken from a previous study (9). Chewing movements were measured by time (seconds), number of cycles, and a time/cycle ratio. A chewing cycle was defined as an upward and downward movement of the chin. Total time from the moment food was placed in the mouth until the final swallow occurred was divided by the number of cycles counted for the same period. The type of food eaten affected time, cycles, and the time/cycle ratio, but age and sex did not. A comparison of younger (2- and 3-year-olds) and older children (4- and 5-year-olds) showed significant time differences. During maturation, time was shortened. It was shown earlier that under pathologic conditions (Down's syndrome) time was prolonged. Thus, the time/cycle ratio is an excellent indicator of the developmental status of a child.


The PRISMA Symposium 2: lessons from beyond Europe. reflections on the evolution of palliative care research and policy in Canada.
In Canada, the aging population with a rising incidence of chronic diseases-and thus more complex care needs-is putting significant pressure on the health care system, long-term care system, and family caregivers. Ten years ago, the Government of Canada appointed Canada's first Minister with Special Responsibility for Palliative Care. During that time, the federal government developed significant public policy goals for palliative care, including the Canadian Strategy on Palliative and End-of-Life Care. This strategy led to many policy improvements, particularly in the areas of research and data collection, education for health care professionals, and support for caregivers. In 2007, the Secretariat within the federal government supporting the Canadian strategy was defunded and disbanded. Four years later, progress in improving palliative care for Canadians has slowed. This article reviews some of the successes of palliative care policy and research in Canada and outlines several lessons to be learned for other jurisdictions developing public policy for palliative care.


High-pulse-energy, linear optical parametric oscillator with narrow and symmetrical far field.
A new method to obtain a narrow and symmetrical far field from a high-pulse-energy optical parametric oscillator (OPO) with a linear resonator has been tested. The OPO employs two identical nonlinear crystals that are cut for type II phase matching, rotated such that their walk-off planes are orthogonal, and separated by a broadband half-wave plate. The OPO has a simple geometry, can be double-pass pumped, is wavelength tunable and operates stably with high conversion efficiency. The method has been demonstrated in a KTP-based OPO pumped at 1064 nm and a BBO-based OPO pumped at 532 nm, with output pulse energies up to 60 mJ and 75 mJ, respectively.


Low-Intensity Nanosecond Pulsed Electric Field Accelerates Osteogenic Transformation of Human Dermal Fibroblasts by Enhancing Cell Pluripotency.
Autologous human fibroblasts have the potential to differentiate into the osteogenic lineage under specific conditions and can be utilized for bone regeneration. However, their efficiency is currently unsatisfactory. Recently, low-intensity nanosecond pulsed electric field (nsPEF) stimulation has been demonstrated to enhance cell pluripotency by activating epigenetic regulatory pathways. In this study, human dermal fibroblasts were exposed to different intensities of nsPEF to assess whether these exposures resulted in changes in proliferation rate, calcium salt deposition, and expression of differentiation-related markers in different experimental groups. The results showed a significant increase in cell proliferation, pluripotency, bone marker expression, and osteogenic differentiation efficiency when stimulating cells with 5 kV/cm of nsPEF. However, cell proliferation and differentiation significantly decreased at 25 kV/cm. Additionally, the proliferation and efficiency of osteogenic differentiation were reduced when the nsPEF intensity was increased to 50 kV/cm. Treatment with a 5 kV/cm of nsPEF led to increased and concentrated expression of Yes-Associated Protein (YAP) in the nucleus. These observations suggest that human dermal fibroblasts possess a heightened potential to differentiate into osteogenic cells when activated with nsPEF at 5 kV/cm. Consequently, the nsPEF strengthening strategy shows promise for fibroblast-based tissue-engineered bone repair research.


Polarity transition records and the geomagnetic dynamo.
The Parker-Levy approach to reversals of the geomagnetic field predicts meridional transitional paths of the virtual geomagnetic pole (VGP) which pass either through the site of observation or through its antipode, depending upon the site location and the sense of the polarity transition. Comparison with the most detailed transitional VGP path records presently available gives some indication of the above behavior as predicted by the Parker-Levy model. Discrepancies may be due to complexities in the distribution of cyclonic convection cells in the core not considered in the formal mathematical treatment. The predicted variation in transitional field intensity experienced at any given site also is compatible with several reported transition records.


[Value of the assay of bone aluminum by pulse polarography].
Pulse polarography has been applied to the determination of aluminium in bone. The sensitivity, selectivity and reproducibility of the method are described. The results of bone aluminium concentrations in controls and in haemodialysed patients treated with aluminium compounds are discussed. Pulse polarography permits very precise measurements of aluminium impregnating bone.


Efficacy and safety of biodegradable polymer biolimus A9-eluting stent versus durable polymer everolimus-eluting stent in diabetic patients: a prospective non-randomized single-centre long-term comparison.
Biodegradable polymer drug-eluting stents may improve biocompatibility and reduce the risk of very late stent thrombosis (ST) but outcomes are nevertheless unknown in diabetic patients. The purpose of this study was to assess the long-term efficacy and safety of the biodegradable polymer biolimus A9-eluting stent (BP-BES) in comparison with the current reference durable polymer everolimus-eluting stent (DP-EES) in diabetic patients. 119 BP-BES and 178 DP-EES were implanted respectively in 105 and 146 diabetic patients presenting similar clinical and peri-procedural characteristics. The median follow-up time was 20.8 months. No statistically significant difference was observed between the BP-BES and DP-EES groups in terms of occurrence of the composite primary end point of cardiac death, spontaneous myocardial infarction and clinically indicated target lesion revascularization (8 patients [8%] in the BP-BES group versus 24 patients [17%] in the DP-EES group; HR 1.36, 95% CI 0.59-3.15, P = 0.47) and of the rate of ST (5 patients [5%] in the BP-BES group versus 11 patients [8%] in the DP-EES group; HR 0.73, 95% CI 0.22-2.37, P = 0.60). In spite of a trend in favour of the BP-BES, long-term efficacy and safety were similar for both the BP-BES and the DP-EES in this specific population of diabetic patients. Considering the low incidence of the studied clinical events, other studies with larger population sizes are needed to confirm this observation.


The newly designed univalved artificial heart.
A univalved artificial heart (AH) powered electromagnetically in the frequency range of 1-30 Hz was developed to obtain a totally implantable AH. This small sized AH consisted of a vibrating tube, coils, magnets, and a jellyfish valve as an outlet AH valve. The fluid mechanical, hemodynamic, and hematologic properties were evaluated in a mock circulation and 10 animal experiments using adult goats. This vibrating electromagnetic AH could generate more than 10 L/min as an output volume, with 10 Hz vibration using 20 volts supplied voltage. It could also provide two kinds of flow and pressure patterns, in constant-peak and periodic-peak patterns. The values of free hemoglobin remained within acceptable limits. The authors concluded that this new type of pump was useful as a totally implantable AH, ventricular assist, or organ assist system.


The relationship between different facets of empathy, pain perception and compassion fatigue among physicians.
Medical practitioners such as physicians are continuously exposed to the suffering and the distress of patients. Understanding the way pain perception relates to empathetic dispositions and professional quality of life can contribute to the development of strategies aimed at protecting health professionals from burnout and compassion fatigue. In the present study we investigate the way individual dispositions relate to behavioral measures of pain sensitivity, empathy, and professional quality of life. A secure Web-based series of self-report measures and a behavioral task were administered to 1,199 board-certified physicians. Additionally, surveys were used to obtain measures of demographic and professional background; dispositional empathy (empathic concern, personal distress, and perspective taking); positive (compassion satisfaction) and negative (burnout and secondary traumatic stress) aspects of their professional life. In the behavioral task, participants were asked to watch a series of video clips of patients experiencing different levels of pain and provide ratings of pain intensity and induced personal distress. Perceived pain intensity was significantly lower among more experienced physicians but similar across specialty fields with varying demands of emotional stress. Watching videos of patients in pain, however, elicited more personal distress among physicians in highly demanding medical fields, despite comparable empathy dispositions with other fields. The pain of male patients was perceived as less intense than the pain of female patients, and this effect was more marked for female physicians. The effect of dispositional empathy on pain perception and induced personal distress was different for each sub-component, with perspective taking and empathic concern (EC) being predictive of the behavioral outcomes. Physicians who experience both compassion satisfaction and fatigue perceive more pain and suffer more personal distress from it than those who only suffer the negative aspects of professional quality of life. Professional experience seems to desensitize physicians to the pain of others without necessarily helping them down-regulate their own personal distress. Pain perception is also related with specific aspects of empathy and varies depending on context, as is the case with the gender of their patients. Minimum levels of empathy appear necessary to benefit from the positive aspects of professional quality of life in medicine.


Polysaccharides and Phenolic Compounds Recovered from Red Bell Pepper, Tomato and Basil By-Products Using a Green Extraction by Extractor Timatic®.
Fruits and vegetables processing produces significant amounts of by-products rich in valuable bioactive compounds such as polyphenols and dietary fiber. Food by-product re-use promotes the eco-sustainability of several crops. This study aimed to apply green extractions of bioactive compounds from by-products of basil, tomato, and red bell pepper production. Tests were performed by applying extraction procedures both at laboratory scale and using the Timatic® extractor. Water and ethanol 10% and 20% were used for extraction of red bell pepper and tomato, testing different temperatures (30, 50, and 90 °C; water at 90 °C and ethanol 20% were applied for basil. The obtained phenolic extracts were analyzed by HPLC-DAD-MS. Polysaccharides of tomato and red bell pepper were extracted at laboratory scale and chemically characterized using 1H-NMR to define the methylation and acylation degree, and DLS to estimate the hydrodynamic volume. Laboratory extraction tests allowed efficient scaling-up of the process on the Timatic® extractor. Phenolic content in the dried extracts (DE) ranged 8.0-11.2 mg/g for tomato and red bell pepper and reached 240 mg/g for basil extracts. Polysaccharide yields (w/w on DM) reached 6.0 and 10.4% for dried tomato and red bell pepper, respectively. Dry extracts obtained using the Timatic® extractor and water can be useful sources of bioactive phenols. The study provided new data on tomato and red bell pepper polysaccharides that may be useful for future applications.


Vision guides the adjustment of auditory localization in young barn owls.
Barn owls raised with one ear plugged make systematic errors in auditory localization when the earplug is removed. Young owls correct their localization errors within a few weeks. However, such animals did not correct their auditory localization errors when deprived of vision. Moreover, when prisms were mounted in front of their eyes, they adjusted their auditory localization to match the visual error induced by the prisms, as long as the visual and auditory errors were within the same quadrant of directions. The results demonstrate that, during development, the visual system provides the spatial reference for fine-tuning auditory localization.


[Applying the nursing process to patient care in the operating room].
The article proposes to approach the application of the nursing process to patient care in the operating room, it gives a theorical basis and examples from the clinical pratices.


Get Yourself Tested 2011-2012: findings and prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae at an urban public health system.
During April 2011 and April 2012 the Get Yourself Tested campaign was launched throughout the Cook County Health and Hospitals System to promote testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) among 15-25-year-olds in a high-prevalence urban community. Retrospective data were collected and analysed. Demographic differences by CT and GC positivity were evaluated along with factors associated with CT and GC status. A total of 2853 tests were conducted among individuals aged 15-25 years. A total of 2060 (72%) females and 793 (28%) males were tested. Of those tested, 488 (17%) individuals tested positive for either CT or GC or both; 400 (14%) were positive for CT, 139 (5%) were positive for GC. The prevalence for GC was 8.8% (n = 70) in males compared to 3.3% (n = 69) in females (p < 0.001) and the prevalence of CT was 16% (n = 127) for males compared to 13.3% (n = 273) for females (p = 0.057). Women in a high-risk population are more likely to get tested for sexually transmitted infections; however, men are more likely to test positive for CT and GC. Get Yourself Tested is an important campaign to encourage wider spread testing among populations at risk in Cook County.


Phase singularity diffusion.
We follow the trajectories of phase singularities at nulls of intensity in the speckle pattern of waves transmitted through random media as the frequency of the incident radiation is scanned in microwave experiments and numerical simulations. Phase singularities are observed to diffuse with a linear increase of the square displacement 〈R2〉 with frequency shift. The product of the diffusion coefficient of phase singularities in the transmitted speckle pattern and the photon diffusion coefficient through the random medium is proportional to the square of the effective sample length. This provides the photon diffusion coefficient and a method for characterizing the motion of dynamic material systems.


Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound.
Ultrasound insonation of microbubbles can form transient pores in cell membranes that enable the delivery of non-permeable extracellular molecules to the cells. Reducing the size of microbubble contrast agents to the nanometer range could facilitate cancer sonoporation. This size reduction can enhance the extravasation of nanobubbles into tumors after an intravenous injection, thus providing a noninvasive sonoporation platform. However, drug delivery efficacy depends on the oscillations of the bubbles, the ultrasound parameters and the size of the target compared to the membrane pores. The formation of large pores is advantageous for the delivery of large molecules, however the small size of the nanobubbles limit the bioeffects when operating near the nanobubble resonance frequency at the MHz range. Here, we show that by coupling nanobubbles with 250 kHz low frequency ultrasound, high amplitude oscillations can be achieved, which facilitate low energy sonoporation of cancer cells. This is beneficial both for increasing the uptake of a specific molecule and to improve large molecule delivery. The method was optimized for the delivery of four fluorescent molecules ranging in size from 1.2 to 70 kDa to breast cancer cells, while comparing the results to targeted microbubbles. Depending on the fluorescent molecule size, the optimal ultrasound peak negative pressure was found to range between 300 and 500 kPa. Increasing the pressure to 800 kPa reduced the fraction of fluorescent cells for all molecules sizes. The optimal uptake for the smaller molecule size of 4 kDa resulted in a fraction of 19.9 ± 1.8% of fluorescent cells, whereas delivery of 20 kDa and 70 kDa molecules yielded 14 ± 0.8% and 4.1 ± 1.1%, respectively. These values were similar to targeted microbubble-mediated sonoporation, suggesting that nanobubbles can serve as noninvasive sonoporation agents with a similar potency, and at a reduced bubble size. The nanobubbles effectively reduced cell viability and may thus potentially reduce the tumor burden, which is crucial for the success of cancer treatment. This method provides a non-invasive and low-energy tumor sonoporation theranostic platform, which can be combined with other therapies to maximize the therapeutic benefits of cancer treatment or be harnessed in gene therapy applications.


[The effect of the administration of different estrogens on the content of estrogen receptors in the cytosol and nuclear subfractions of liver cells and on the level of angiotensinogen in the blood plasma of rats].
The level of estrogen receptors (ER) in the cytosol and nuclear subfractions of female rat hepatocytes was studied 1 h and plasma angiotensinogen (AG) concentration 24 h after single and multiple administration of different doses of estradiol (E2) and synthetic estrogens. Synthetic weakly metabolized estrogens, used at doses corresponding to physiological concentrations of the natural female sex steroid, were shown to be much more effective than E2 in relation to ER redistribution between the cytosol and nuclear fractions of hepatocytes as well as in relation to the stimulation of AG production by the liver. Differences in the ER level in hepatocytic nuclei 1 h after single or multiple administration of the same estrogen were undetectable. An increase in a plasma AG level after a single injection of estrogens was noted after achieving a certain threshold (more than 3-fold as compared to the normal level) level of ER accumulation in hepatocytic nuclei. The sensitivity of AG production by the liver to a stimulating effect of low doses of estrogens was on the increase as a result of their repeated effect in prolonged administration and combined administration of E2 and glucocorticoids.


Calpain 10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabetic-related conditions.
The association of the gene encoding calpain 10 with type 2 diabetes mellitus (T2DM) has been reported. In this study we aimed to evaluate the association of SNP-19,-44, and -63 polymorphisms of calpain 10 with type 2 diabetes and diabetic-related conditions, such as diabetic retinopathy, nephropathy, and neuropathy in a Turkish population. The study group included 202 patients (133 female and 69 male) with T2DM, while the control group included 80 nondiabetic people (44 female and 36 male). Genotyping was done by the polymerase chain reaction and restriction fragment length polymorphism method. Calpain 10 SNP-44 TC genotype was found to be significantly frequent in type 2 diabetic patients with respect to the control group (p < 0.01). Body mass index (BMI) was found to be significantly high in TC genotype with type 2 diabetic patients (p < 0.05). SNP-44 T allele frequency was found to be lower in type 2 diabetic patients compared with the controls (p < 0.01). We conclude that the calpain 10 SNP-44 gene polymorphism may be accepted as a risk factor in the development of T2DM and elevated BMI in type 2 diabetic patients in a Turkish population.


Distribution of photoperiod-insensitive allele Ppd-A1a and its effect on heading time in Japanese wheat cultivars.
The Ppd-A1 genotype of 240 Japanese wheat cultivars and 40 foreign cultivars was determined using a PCR-based method. Among Japanese cultivars, only 12 cultivars, all of which were Hokkaido winter wheat, carried the Ppd-A1a allele, while this allele was not found in Hokkaido spring wheat cultivars or Tohoku-Kyushu cultivars. Cultivars with a photoperiod-insensitive allele headed 6.9-9.8 days earlier in Kanto and 2.5 days earlier in Hokkaido than photoperiod-sensitive cultivars. The lower effect of photoperiod-insensitive alleles observed in Hokkaido could be due to the longer day-length at the spike formation stage compared with that in Kanto. Pedigree analysis showed that 'Purple Straw' and 'Tohoku 118' were donors of Ppd-A1a and Ppd-D1a in Hokkaido wheat cultivars, respectively. Wheat cultivars recently developed in Hokkaido carry photoperiod-insensitive alleles at a high frequency. For efficient utilization of Ppd-1 alleles in the Hokkaido wheat-breeding program, the effect of Ppd-1 on growth pattern and grain yield should be investigated. Ppd-A1a may be useful as a unique gene source for fine tuning the heading time in the Tohoku-Kyushu region since the effect of Ppd-A1a on photoperiod insensitivity appears to differ from the effect of Ppd-B1a and Ppd-D1a.


Fractal image denoising.
Over the past decade, there has been significant interest in fractal coding for the purpose of image compression. However, applications of fractal-based coding to other aspects of image processing have received little attention. We propose a fractal-based method to enhance and restore a noisy image. If the noisy image is simply fractally coded, a significant amount of the noise is suppressed. However, one can go a step further and estimate the fractal code of the original noise-free image from that of the noisy image, based upon a knowledge (or estimate) of the variance of the noise, assumed to be zero-mean, stationary and Gaussian. The resulting fractal code yields a significantly enhanced and restored representation of the original noisy image. The enhancement is consistent with the human visual system where extra smoothing is performed in flat and low activity regions and a lower degree of smoothing is performed near high frequency components, e.g., edges, of the image. We find that, for significant noise variance (sigma > or = 20), the fractal-based scheme yields results that are generally better than those obtained by the Lee filter which uses a localized first order filtering process similar to fractal schemes. We also show that the Lee filter and the fractal method are closely related.


Effect of the Nordmøre grid bar spacing on size selectivity, catch efficiency and bycatch of the Barents Sea Northern shrimp fishery.
The introduction of the Nordmøre grid in shrimp trawls has reduced the bycatch of non-target species. In the Norwegian Northern shrimp (Pandalus borealis) fishery, the mandatory selective gear consists of a Nordmøre grid with 19 mm bar spacing combined with a 35 mm mesh size diamond mesh codend. However, fish bycatch in shrimp trawls remains a challenge and further modifications of the gear that can improve selectivity are still sought. Therefore, this study estimated and compared the size selectivity of Nordmøre grids with bar spacings of 17 and 21 mm. Further, the effect of applying these two grids on trawl size selectivity was predicted and compared to the legislated gear configuration. Experimental fishing trials were conducted in the Barents Sea where the bottom trawl fleet targets Northern shrimp. Results were obtained for the target species and two by-catch species: cod (Gadus morhua) and American plaice (Hippoglossoides platessoides). This study demonstrated that reducing bar spacing can significantly reduce fish bycatch while only marginally affecting catch efficiency of Northern shrimp. This is a potentially important finding from a management perspective that could be applicable to other shrimp fisheries where flexibility in the use of different grid bar spacings may be beneficial to maximize the reduction of unwanted bycatch while minimizing the loss of target species.


trans Activation of the simian virus 40 enhancer.
We describe experiments which demonstrated that the simian virus 40 (SV40) enhancer affects certain transcriptional units differently. We also found that a specific enhancer-transcriptional unit interaction can be regulated by trans-acting factors. Using transient assays, we examined the effects of the SV40 enhancer on herpesvirus thymidine kinase (tk) RNA levels when transcription was initiated either by the herpesvirus tk promoter or by an SV40 early promoter-tk fusion. We were unable to detect any effect of the enhancer on transcription from the tk promoter in CV-1 or HeLa cells. However, we found that the addition of T-antigen in trans allowed the enhancer to stimulate expression from the tk promoter. This induction by T-antigen did not require T-antigen-binding sites in cis and appeared to be an indirect effect. In contrast, tk expression from the SV40 early promoter fusion was greatly stimulated by the enhancer in CV-1 cells. Furthermore, in 293 cells the SV40 enhancer had only a marginal effect on the SV40 promoter-tk fusion, whereas it strongly stimulated tk expression from the tk promoter. Our results raise the possibility that the enhancer function may not show cell specificity per se; rather, the interaction between the enhancer and a specific gene may be responsible for cell specificity. We discuss these observations in terms of the SV40 early gene-to-late gene switch that occurs during SV40 lytic growth.


Pulmonary vascular complications in narcotic addicts.
Perfusion deficits on lung scanning in narcotic addicts are frequently demonstrable. To determine the angiographic and hemodynamic correlates of these deficits, right heart catheterization with selective pulmonary angiography was carried out in 7 addicts with abnormal lung scans, and one with normal scan. Four had angiographic abnormalities corresponding to the regions of perfusion defects on lung scan. These consisted of large vessel cut-offs, intraluminal filling defects and/or considerably reduced vascularity. Three subjects had normal angiograms in the presence of abnormal perfusion scans. One subject had normal angiogram and scan. All eight patients had normal pulmonary artery pressures and calculated pulmonary vascular resistances. This study demonstrates that (1) angiographic abnormalities in larger pulmonary arteries may be found in narcotic addicts with perfusion defects on lung scanning, and (2) these findings may be present without significant hemodynamic alterations.


The long-term social and economic impact of HIV on the spouses of infected individuals in northern Malawi.
To assess the social and economic impact of HIV-related illness and death on the spouses of HIV-infected individuals. From population-based surveys in the 1980s in Karonga district, northern Malawi, 197 'index individuals' were identified as HIV-positive. A total of 396 HIV-negative 'index individuals' were selected as a comparison group. These individuals, and their spouses and children, were followed up in 1998-2000, in a retrospective cohort study. All analyses compared spouses of HIV-positive indexes with those of HIV-negative indexes. By 1998-2000, most marriages involving an HIV-positive index individual had ended in widowhood. Twenty-Six percent of the wives of HIV-positive index men experienced household dissolution precipitated by widowhood, compared with 5% of the wives of HIV-negative index men. Corresponding percentages for husbands of index women were 14% and 1%. Widow inheritance was uncommon. The remarriage rate among separated or widowed wives of HIV-positive index men was half that of such wives of HIV-negative index men. About 30% of surviving wives of HIV-positive index men were household heads at the time of follow-up, compared with 5% of such wives of HIV-negative index men. Almost all these women were widows who lost their husband when >35 years old, and they had relatively few household assets. The social and economic impact of HIV on the spouses of HIV-infected individuals in rural northern Malawi is substantial. Interventions that strengthen society's ability to absorb and support widows and widowers, and their dependents, without necessarily involving the traditional coping mechanism of remarriage, are essential.


Exposure to a mnemonic interferes with recall of suicide warning signs in a community-based suicide prevention program.
The incremental impact of adding a mnemonic to remember suicide warning signs to the Air Force Suicide Prevention Program (AFSPP) community awareness briefing was investigated with a sample of young, junior-enlisted airmen. Participants in the standard briefing significantly increased their ability to list suicide warning signs and improved consistency with an expert consensus list, whereas participants in the standard briefing plus mnemonic demonstrated no learning. Both groups demonstrated positive changes in beliefs about suicide. Results suggest that inclusion of the mnemonic in the AFSPP briefing interfered with participants' ability to learn suicide warning signs, and that increased confidence in the perceived ability to recognize suicide risk is not related to actual ability to accurately recall warning signs.


A fatality due to the use of cantharides from Mylabris phalerata as an abortifacient.
A fatal case of attempting to procure abortion by the ingestion of the crude extract of cantharides from over 200 dried Mylabris phalerata is presented. The quantification of catharidin in blood, urine and liver by gas chromatography using trichloroacetic acid in the extraction process and butobarbitone as the internal standard is described. Ante- and post-mortem blood levels were found to be 0.27 and 0.11 micrograms/ml respectively. To conclude, the lack of legislative control in Hong Kong over Chinese herbal medicines is highlighted.


Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury.
Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa-/- and Itgam-/- mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.


Alcohol, affect, and the disinhibition of verbal behavior.
A study was conducted to investigate the effects of acute alcohol administration on affective states and verbal behavior during the ascending and descending limbs of the blood alcohol curve. Sixteen male social drinkers were given alcohol (1.0 g/kg) or placebo in a double-blind crossover research design. Subjects tested while blood alcohol levels (BAL) were ascending close to peak concentration (0.11 g%) described themselves as more elated, friendly, and vigorous than when tested under placebo conditions. As BAL declined, subjects described themselves as more angry, depressed, and fatigued. Cognitive confusion, hostile verbal interaction, and aggressive thematic content were also greater during alcohol intoxication, but these measures were unrelated to direction of change in the BAL curve. It was concluded that (1) the effects of alcohol on affect are biphasic and are closely related to direction of change in the BAL curve, (2) the disinhibition of certain types of verbal behavior is related neither to affective state or to direction of the BAL curve, and (3) the perception of cognitive disorientation may mediate the effects of alcohol on those behaviors normally suppressed by various controlling influences.


Utilizing Deep Learning to Identify an Ultrasound-guided Nerve Block Target Zone.
Ultrasound guided nerve blocks are increasingly being used in perioperative care as a means of safely delivering analgesia. Unfortunately, identifying nerves in ultrasound images presents a challenging task for novice anesthesiologists. Drawing from online resources, here we attempted to address this issue by developing a deep learning algorithm capable of automatically identifying the transversus abdominis plane region in ultrasound images. Training of our dataset was done using the U-Net architecture and artificial augmentation was done to optimize our training dataset. The Dice score coefficient was used to evaluate our model, with further evaluation against a test set composed of manually drawn labels from a pool of (n=10) expert anesthesiologists.Across all labelers the model achieved a global Dice score of 73.31% over the entire test set. These preliminary results highlight the potential effectiveness of this model as a future ultrasound decision support system in the field of anesthesia.


Bell's palsy: aetiology, clinical features and multidisciplinary care.
Bell's palsy is a common cranial neuropathy causing acute unilateral lower motor neuron facial paralysis. Immune, infective and ischaemic mechanisms are all potential contributors to the development of Bell's palsy, but the precise cause remains unclear. Advancements in the understanding of intra-axonal signal molecules and the molecular mechanisms underpinning Wallerian degeneration may further delineate its pathogenesis along with in vitro studies of virus-axon interactions. Recently published guidelines for the acute treatment of Bell's palsy advocate for steroid monotherapy, although controversy exists over whether combined corticosteroids and antivirals may possibly have a beneficial role in select cases of severe Bell's palsy. For those with longstanding sequaelae from incomplete recovery, aesthetic, functional (nasal patency, eye closure, speech and swallowing) and psychological considerations need to be addressed by the treating team. Increasingly, multidisciplinary collaboration between interested clinicians from a wide variety of subspecialties has proven effective. A patient centred approach utilising physiotherapy, targeted botulinum toxin injection and selective surgical intervention has reduced the burden of long-term disability in facial palsy.


Regional circulatory contributions to increased systemic vascular conductance of pregnancy.
In pregnancy, maternal systemic vascular conductance increases, a new vascular circuit grows, and the maternal systemic circulation develops a diminished pressor response to angiotensin II (ANG II). However, the quantitative contributions of the latter two circulatory changes to the increased systemic vascular conductance of pregnancy have not been explored. In this experiment, we examined regional circulatory contributions to the increased systemic vascular conductance in conscious, late-gestation guinea pigs. Systemic arterial pressure, cardiac output (dye dilution), and regional blood flows (radiolabeled microspheres) were measured during baseline conditions and progressive ANG II infusion. Systemic and regional conductances were calculated from arterial pressure and cardiac output or regional blood flows. In pregnancy, maternal systemic vascular conductance increased from 3.2 to 5.0 ml.min-1.mmHg-1 (P less than 0.001); increased nonuteroplacental conductance contributed 71% to the increase in whole body conductance. Pregnancy tended to decrease the nonuteroplacental conductance response (P = 0.072), but did not change the uteroplacental conductance response (P greater than or equal to 0.29), to ANG II. The increased uteroplacental blood flow of pregnancy was preserved during ANG II-induced vasoconstriction. We conclude that maternal systemic vascular conductance increased primarily because nonuteroplacental vascular conductance increased.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors.
Alterations in the expression of mucin family members play an important role as well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and progression of pancreatic cancer. We analyzed the expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic tumors. MUC1 expression was observed in almost all samples, whereas MUC2 expression was not. MUC5AC expression was observed in 73.9% of the cancerous regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in 37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression of these mucins was not observed in the hyperplastic regions and normal pancreatic duct and was observed in only two dysplastic regions. The survival of pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than that of other patients (P=0.04). In conclusion, the localization of mucin expression, especially stromal expression of MUC1 or SIMA, might be a prognostic factor for patients with pancreatic cancer.


Life-threatening neonatal epidural hematoma caused by precipitous vaginal delivery.
Neonatal in-hospital falls occur relatively frequently, although they are likely underreported. Significant intracranial head trauma from a fall or birth injury is not common in the immediate newborn period. Furthermore, intracranial bleeding requiring surgical intervention is exceedingly rare. We present an unusual case of an in-hospital fall in the delivery room requiring neurosurgical intervention. A term infant, appropriate for gestational age, delivered precipitously from a maternal standing position. The vertex neonate struck the linoleum floor after an approximate 80-cm fall, landing headfirst. The physical and neurological exams were initially normal, and skull films did not demonstrate an obvious fracture. The baby was closely observed, undergoing continuous cardiorespiratory monitoring. After the patient had an episode of apnea, a scalp hematoma was noted. A computed tomography (CT) scan revealed a left parietal fracture with an acute epidural hematoma, which required emergent craniotomy. The infant had an unremarkable post-operative course and had a normal neurodevelopmental assessment at 15 months of age. Close, continuous observation is recommended for infants following an in-hospital fall or after significant birth trauma. A high degree of suspicion for intracranial hemorrhage must be maintained. Fall prevention strategies should focus on careful baby handling by the convalescing mother.


Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer.
Hypoxia has long been recognized as detrimental to the successful treatment of malignant tumors with ionizing radiation. Because hypoxia-inducible factor (HIF)-1alpha plays an essential role in oxygen homeostasis in vitro, we explored the predictive potential of this factor in a cohort of 98 patients with squamous cell cancer of the oropharynx, who were treated by curative radiation therapy. Ninety-four % of the primary tumors showed overexpression of HIF-1alpha, relative to the surrounding tissue, as determined by immunohistochemistry. The degree of HIF-1alpha immunoreactivity correlated inversely with both the rate of complete remission of the primary tumor (odds ratio, 0.33; P = 0.03) and lymph node metastases (odds ratio, 0.34; P = 0.02) as well as with local failure-free survival (risk ratio, 2.15; P = 0.006), disease-free survival (risk ratio, 2.01; P = 0.008), and overall survival (risk ratio, 2.17; P = 0.002). The multivariate analysis revealed the predictive power of HIF-1alpha to be independent of other covariables. We conclude that HIF-1alpha is overexpressed in the vast majority of patients with squamous cell cancer of the oropharynx and that the degree of expression has predictive and prognostic significance in individuals undergoing curative radiation therapy.


From Leningrad to London: the saga of Kulchitsky and the legacy of the enterochromaffin cell.
By the end of the 19th century, the subject of internal secretion and the consequences of its perturbations had been explored in considerable depth but with little clear understanding. Despite the anatomic delineation of the majority of the glands and tissues that comprised the gross endocrine system, the cellular basis and the interactions between the 'internal glands' and the nervous system had not been clearly delineated. Prominent early investigators in the field included Rudolf Peter Heidenhain (1834-1897), who described a novel class of clear cells (1868), Paul Langerhans (1847-1888), who identified pancreatic islets in 1869, and M.C. Ciacco (1877-1956), who coined the term 'enterochromaffin' (1906). Their contributions facilitated the description of the diffuse neuroendocrine system (DNES) by F. Feyrter (1938) which allowed for the understanding of a syncytial regulatory system that consisted of both endocrine and neural components. This rich developmental history often reveals the name of Kulchitsky, but little recognition has been given to his seminal contributions. Indeed the Russian, Nikolai Konstantinovich Kulchitsky (1856-1925), both due to his modest and unassuming nature and the tragic events of his life, was little recognized and has been relegated to a mere eponymous attribution. In reality, his life bears legacy to rich scientific contributions spanning a great teaching and scientific career at Kharkov University, to responsibilities as the Imperial Minister of Education for all of Russia. He identified the Kulchitsky cell, trained and mentored numerous professors of histopathology, was incarcerated by the Bolsheviks and worked in a soap factory to save his life. He and his family finally fled on a British battleship with the remnants of the Russian Royal family to England where he secured a position with Bayliss and Starling at University College, London (UCL). His mysterious demise in a lift-shaft accident on his 69th birthday tragically terminated a life of great service to science and teaching. He excelled as a histopathologist and was responsible for the early description of tonsillar and gut epithelial leucocytes as well as defining components of the Ascaris life cycle. At UCL, his contributions to the anatomic delineation of muscle nerve endings were highly regarded and widely admired. It is, however, his identification of the enterochromaffin cell in 1897 for which he is most remembered since this observation formed the basis for the subsequent delineation of the DNES and provided the cellular framework on which the discipline of gut neuroendocrinology would be established.


INDI: a computational framework for inferring drug interactions and their associated recommendations.
Inferring drug-drug interactions (DDIs) is an essential step in drug development and drug administration. Most computational inference methods focus on modeling drug pharmacokinetics, aiming at interactions that result from a common metabolizing enzyme (CYP). Here, we introduce a novel prediction method, INDI (INferring Drug Interactions), allowing the inference of both pharmacokinetic, CYP-related DDIs (along with their associated CYPs) and pharmacodynamic, non-CYP associated ones. On cross validation, it obtains high specificity and sensitivity levels (AUC (area under the receiver-operating characteristic curve) ≥0.93). In application to the FDA adverse event reporting system, 53% of the drug events could potentially be connected to known (41%) or predicted (12%) DDIs. Additionally, INDI predicts the severity level of each DDI upon co-administration of the involved drugs, suggesting that severe interactions are abundant in the clinical practice. Examining regularly taken medications by hospitalized patients, 18% of the patients receive known or predicted severely interacting drugs and are hospitalized more frequently. Access to INDI and its predictions is provided via a web tool at http://www.cs.tau.ac.il/~bnet/software/INDI, facilitating the inference and exploration of drug interactions and providing important leads for physicians and pharmaceutical companies alike.


The purchase sources of and price paid for cigarettes in six European countries: Findings from the EUREST-PLUS ITC Europe Surveys.
Tobacco tax policies have been proven to be effective in reducing tobacco consumption, but their impact can be mitigated through price-minimizing behaviours among smokers. This study explored the purchase sources of tobacco products and the price paid for tobacco products in six EU member states. Data from Wave 1 of the EUREST-PLUS ITC Europe Survey collected from nationally representative samples of adult smokers in Germany, Greece, Hungary, Poland, Romania and Spain (ITC 6E Survey) were used. The ITC 6E Survey sample, conducted in 2016, randomly sampled 6011 adult cigarette smokers aged 18 years or older. Information on purchase sources of tobacco was examined by country. The difference in reported purchase price by purchase location (store vs non-store/other) was analysed using linear regression for each country. Tobacco purchasing patterns and sources varied widely between countries. Non-store/other purchases were very rare in Hungary (0.1%) while these types of purchases were more common in Germany (5.1%) and Poland (8.6%). Reported prices of one standard pack of 20 cigarettes were highest in Germany (4.80€) and lowest in Hungary (2.45€). While non-store purchases were only made by a minority of smokers (>10% in all countries), the price differential was considerable between store and non-store/other sources, up to 2€ per pack in Greece and in Germany. The results suggest a huge variation of purchasing sources and price differentials between store and non-store purchasing sources across the six EU member states examined. While the cross-sectional data precludes any causal inference, supply chain control through licensing as introduced in Hungary and the lack of such measures in the other countries might nevertheless be a plausible explanation for the large differences in the frequency of non-store purchases observed in this study.


Differences in the control of virus mRNA splicing during permissive or abortive infection with influenza A (fowl plague) virus.
Spliced transcripts of influenza A (fowl plague) virus (FPV) RNA (vRNA) segments 7 and 8 accumulate to a much greater extent during non-productive infection of mouse L cells, than they do during productive infection in primary chick embryo fibroblasts (CEF). Virus-specific protein synthesis, or a consequent event in virus replication appears necessary to promote splicing of vRNA segment 8-encoded mRNAs in both cell types, and of vRNA segment 7-encoded mRNAs in CEF. In L cells, however, splicing of the segment 7-encoded mRNAs seems to be independent of such virus-specific control. This observation is discussed in relation to the defect in expression of vRNA 7 which has been observed previously in FPV-infected L cells, and which is thought to account for the failure of virus replication.


Phenolics removal from transgenic Lemna minor extracts expressing mAb and impact on mAb production cost.
Transgenic Lemna minor has been used successfully to produce several biotherapeutic proteins. For plant-produced mAbs specifically, the cost of protein A capture step is critical as the economic benefits of plant production systems could be erased if the downstream processing ends up being expensive. To avoid potential modification of mAb or fouling of expensive protein A resins, a rapid and efficient removal of phenolics from plant extracts is desirable. We identified major phenolics in Lemna extracts and evaluated their removal by adsorption to PVPP, XAD-4, IRA-402, and Q-Sepharose. Forms of apigenin, ferulic acid, and vitexin comprised ∼ 75% of the total phenolics. Screening of the resins with pure ferulic acid and vitexin indicated that PVPP would not be efficient for phenolics removal. Analysis of the breakthrough fractions of phenolics adsorption to XAD-4, IRA-402, and Q-Sepharose showed differences in adsorption with pH and in the type of phenolics adsorbed. Superior dynamic binding capacities (DBC) were observed at pH 4.5 than at 7.5. To evaluate the cost impact of a phenolics removal step before protein A chromatography, a mAb purification process was simulated using SuperPro Designer 7.0. The economic analysis indicated that addition of a phenolics adsorption step would increase mAb production cost only 20% by using IRA-402 compared to 35% for XAD-4 resin. The cost of the adsorption step is offset by increasing the lifespan of protein A resin and a reduction of overall mAb production cost could be achieved by using a phenolics removal step.


DNA sequence analysis of an immediate-early gene region of the herpes simplex virus type 1 genome (map coordinates 0.950 to 0.978).
The nucleotide sequence of 4 kilobases of DNA from within the short region of the genome of herpes simplex virus type 1 has been determined. This portion of DNA contains the junctions of the terminal and inverted repeat sequence components with the unique sequence component and the 5'-regions of the genes which encode the Vmw 12, Vmw 68 and Vmw 175 immediate-early polypeptides. The transcription and translation initiation sites of all three genes and the 5' and 3' boundaries of the Vmw 12 and Vmw 68 gene introns have been localized on the DNA sequence and shown to be flanked by sequences which resemble those found in similar positions in other eukaryotic genes. For the Vmw 12 and Vmw 68 genes the promoters, the 5'-non-coding regions of the mRNAs, and the introns lie within the terminal and internal inverted repeats respectively while the polypeptide-coding regions lie in the short unique component. The introns consist largely of tandemly reiterated copies of a 22-nucleotide sequence: the Vmw 12 gene intron contains seven of these and the Vmw 68 gene intron five. The Vmw 175 gene is located entirely within the short repeats, of which those regions sequenced here have the extremely high G + C content of 78%, in marked contrast to the value of 66% obtained for the adjacent region of the unique sequence component. Prediction of the complete amino acid sequence of the Vmw 12 polypeptide, accounting for a mol. wt. of 9830, and of the first 523 amino-terminal amino acids of the Vmw 175 polypeptide has been made from the DNA sequence. The polypeptide-coding region of the Vmw 175 gene has an average G + C content of 80% but nevertheless specifies a wide range of amino acid types because of the maximal assignment of G and C residues to colon third base positions.


Adopting wearables to customize health insurance contributions: a ranking-type Delphi.
Wearables, as small portable computer systems worn on the body, can track user fitness and health data, which can be used to customize health insurance contributions individually. In particular, insured individuals with a healthy lifestyle can receive a reduction of their contributions to be paid. However, this potential is hardly used in practice. This study aims to identify which barrier factors impede the usage of wearables for assessing individual risk scores for health insurances, despite its technological feasibility, and to rank these barriers according to their relevance. To reach these goals, we conduct a ranking-type Delphi study with the following three stages. First, we collected possible barrier factors from a panel of 16 experts and consolidated them to a list of 11 barrier categories. Second, the panel was asked to rank them regarding their relevance. Third, to enhance the panel consensus, the ranking was revealed to the experts, who were then asked to re-rank the barriers. The results suggest that regulation is the most important barrier. Other relevant barriers are false or inaccurate measurements and application errors caused by the users. Additionally, insurers could lack the required technological competence to use the wearable data appropriately. A wider use of wearables and health apps could be achieved through regulatory modifications, especially regarding privacy issues. Even after assuring stricter regulations, users' privacy concerns could partly remain, if the data exchange between wearables manufacturers, health app providers, and health insurers does not become more transparent.


Monoclonal antibodies reactive with swine lymphocytes. II. Detection of an antigen on resting T cells down-regulated after activation.
The expression of an antigen on porcine T lymphocytes detected by murine monoclonal antibody (mAb) 8/1 was investigated by functional studies and dual-parameter immunofluorescence. mAb 8/1 reacts with greater than 95% of thymocytes and in peripheral blood with all T lymphocytes and with cells of the monocyte/macrophage lineage, but not with B cells, erythrocytes, and platelets. Pretreatment of peripheral blood lymphocytes with mAb 8/1 plus complement abrogated the proliferative response in vitro to mitogen, soluble antigen, and MHC determinants. Dual-parameter immunofluorescence revealed that resting porcine T8+ as well as T4+ lymphocytes express the 8/1 antigen, whereas after in vitro activation, cell surface expression of the antigen was low or absent in both T cell subsets. Thus, the 8/1 antigen represents a marker that discriminates between resting and activated T lymphocytes. Distribution and functional criteria indicate that 8/1 represents a novel marker not described before for any other mammalian species.


Retrospective study of the treatment of urethral cancer.
Urethral cancer is rare, encompassing less than 1% of all malignancies. Optimal management, at present, often relies on the limited experience gained from the study of retrospective cases. Therefore, it is imperative to share all available information regarding urethral cancer treatment via reportage of pertinent cases, thus enabling more complete comprehension and decision-making options by both clinicians and researchers. A retrospective review of 18 consecutive patients with primary urethral cancer was performed. An analysis was performed of clinical stage, treatment modality, and outcome. Overall patient survival rate for this retrospective was 44%, with a mean follow-up of 63.5 months. Seven of 10 patients with low-stage diagnosis remained disease free. Comparatively, only one of eight patients with high-stage cancer had no apparent disease. Patients with advanced cancer treated with surgery alone had a shorter disease-free survival (23.3 months) versus those treated with combination chemo/radiation therapy (45.2 months). The major characteristic with prognostic impact was statistically found to be low (T1-2, N0, M0) versus high (T3-4, N1, M1) stage, as assessed by Mann-Whitney U test (z = 2.83, p = 0.0023). Clinical staging afforded the strongest prognostic indication of survival. Patients with low-stage disease exhibited increased survival with single-modality therapy. However, patients with advanced cancer benefited from combined treatment using chemotherapy and radiation therapy.