Public health and military health.

This paper summarizes the role of Public Health specialists within the UK Defence Medical Services (DMS). The armed forces have a need for expert advice on health improvement, health protection and healthcare public health. The first professor of military hygiene, Dr Edmund Parkes, was a leading pioneer in the public health movement of the late 19th century. Since then, the armed forces have evolved the term 'hygiene', though 'health', to 'well-being'. Military doctors with an interest in medical administration and the health of populations have longstanding links with their civilian peers, through the Society of Medical Officers of Health and its successor the Faculty of Public Health. The specialty of Public Health in the armed forces is multidisciplinary, following the same educational pathway as civilian peers. The speciality has made important contributions during global health emergencies including the Ebola outbreak in 2014 and the recent COVID-19 pandemic. Although a small cadre, within the DMS and in the UK Public Health workforce, they have an important role in keeping our armed forces ready for operations. We celebrate the 50th anniversary of the Faculty of Public Health and expect that the DMS will contribute to the further development of the specialty.

Formulating diets for intestinal unavailable nitrogen using blood meal in high-producing dairy cattle.

The high cost of protein feeds and growing concern for the environment have motivated dairy producers and nutritionists to focus their attention on reducing nitrogen (N) losses on dairy farms. It is well recognized that reducing the N content of cattle diets is the single most important factor to increase the efficiency of N use. However, effectively lowering the N content of diets requires the nutritionist to know the availability of N in feeds so as to not negatively affect milk production or overfeed N. To provide reliable data for nutritionists, a new assay to estimate unavailable N in the intestine (uN) was developed. To determine whether uN could be used as a replacement for acid detergent insoluble nitrogen (ADIN) in diet formulation, we conducted a replicated pen study to evaluate the effect of total-tract uN on the performance of high-producing dairy cattle. One hundred twenty-eight cattle that were 97 to 147 d in milk at the beginning of the experiment were allocated into 8 pens of 16 cows, and pens were randomly allocated to 2 dietary treatments. Cattle were fed 1 of 2 isonitrogenous and isocaloric diets that were also equal in neutral detergent fiber, deviating only in the inclusion of 2 different blood meals (BM) used in each diet. The uN contents of the 2 BM were 9% (low uN) and 34% (high uN) total N content as predicted by the assay, whereas when measured as ADIN, no difference in indigestibility was observed. The inclusion of BM was on an isonitrogenous basis, and the predicted difference in uN was 39 g/d or 5.8% of N intake, representing the formulated difference in available N between the 2 treatments. There was no effect of uN on dry matter or N intake, which averaged 27.3 kg/d and 668 g/d for both treatments, respectively. Milk yield and energy-corrected milk were 1.6 and 1.9 kg/d greater for cows fed the low uN diet compared with those fed the high uN diet. The lower uN diet was also associated with greater milk protein yield, greater milk fat yield, and greater milk urea N. The Cornell Net Carbohydrate and Protein System (version 6.5) was used to evaluate the application of the uN measurement by replacing ADIN in BM with the uN value in the inputs for the BM. All other cow and feed chemistry data were inputted as measured in the experiment. The predictions of metabolizable protein-allowable milk demonstrated that using the uN values in place of ADIN increased the accuracy of the prediction and enabled the model to predict the first-limiting nutrient provided all other feed, cattle, and management characteristics were also defined.

Analysis of the Hindriks and van Putten model for propofol anesthesia: Limitations and extensions.

We present a detailed analysis of the Hindriks and van Putten thalamocortical mean-field model for propofol anesthesia [NeuroImage 60(23), 2012]. The Hindriks and van Putten (HvP) model predicts increases in delta and alpha power for moderate (up to 130%) prolongation of GABAA inhibitory response, corresponding to light anesthetic sedation. Our analysis reveals that, for deeper anesthetic effect, the model exhibits an unexpected abrupt jump in cortical activity from a low-firing state to an extremely high-firing stable state (∼250 spikes/s), and remains locked there even at GABAA prolongations as high as 300% which would be expected to induce full comatose suppression of all firing activity. We demonstrate that this unphysiological behavior can be completely suppressed with appropriate tuning of the parameters controlling the sigmoidal functions that map soma voltage to firing rate for the excitatory and inhibitory neural populations, coupled with elimination of the putative population-dependent anesthetic efficacies introduced in the HvP model. The modifications reported here constrain the anesthetized brain activity into a biologically plausible range in which the cortex now has access to a moderate-firing state ("awake") and a low-firing ("anesthetized") state such that the brain can transition from "awake" to "anesthetized" states at a critical level of drug concentration. The modified HvP model predicts a drug-effect hysteresis in which the drug concentration required for induction is larger than that at emergence. In addition, the revised model shows a decrease in the intensity and frequency of alpha-band fluctuations, transitioning to delta-band dominance, with deepening anesthesia. These predicted drug concentration-dependent changes in EEG dynamics are consistent with clinical reports.

Comparison of milk production, intake, and total-tract nutrient digestion in lactating dairy cattle fed diets containing either wheat middlings and urea, commercial fermentation by-product, or rumen-protected soybean meal.

The objective of this study was to evaluate the effects of a commercially available fermentation by-product in a diet containing adequate rumen-degradable protein (RDP) on milk performance, intake, and total-tract nutrient digestion in lactating dairy cattle. Primiparous (n = 48) and multiparous (n = 144) lactating dairy cattle were stratified by milk production and randomly allocated into 12 pens containing 4 primiparous and 12 multiparous animals each. Cattle averaged 118 d in milk and 712 kg of body weight at trial start. Treatment diets, on a dry matter (DM) basis, consisted of 42% corn silage, 13% alfalfa hay and silage, 20% grain corn, and 25% protein premix containing either soybean meal, wheat middlings, and urea (SBM+U), soybean meal and fermentation by-product (SBM+F), or soybean meal and rumen-protected soybean meal (RP-SBM). All 3 diets provided a similar level (DM basis) of neutral detergent fiber analyzed using α-amylase and sodium sulfite and corrected for ash content (31%), crude protein (CP, 14.9%), starch (26%), and metabolizable energy (2.7 Mcal/kg), and differed in sources of RDP. The trial consisted of a 2-wk adaptation and covariate period during which all cows were fed the RP-SBM diet and covariate measurements were taken. Pens were then randomly allocated to treatments, and weekly measurements of milk production, intake, body weight, and condition score were taken for 10 wk. All data were analyzed using the Proc Mixed procedure in SAS (SAS Institute Inc., Cary, NC). Increased DM intake was observed for cows fed SBM+F compared with cows fed SBM+U and RP-SBM (28.3 vs. 26.9 and 26.7 kg/d, respectively). Cows fed SBM+F produced more energy-corrected milk (45.3 kg/d) compared with cows fed SBM+U and RP-SBM (43.6 and 43.7 kg/d, respectively). Milk protein yield was also increased in cows fed SBM+F. No differences were observed with body weight or condition score gain throughout the trial. Apparent total-tract digestibility of fiber was decreased in cows fed SBM+F, likely as a result of increased intake. Responses are consistent with previous research in our laboratory that demonstrated a decrease in ruminal CP degradation, leading to an increase in metabolizable protein supply in the small intestine. The fermentation by-product might be useful in diets containing adequate amounts of RDP from soybean meal or alfalfa. The results from this experiment demonstrate beneficial milk performance responses to fermentation by-product when fed with a source of RDP.

Effects of a commercial fermentation byproduct or urea on milk production, rumen metabolism, and omasal flow of nutrients in lactating dairy cattle.

The objective of this study was to evaluate the effects of a fermentation byproduct on rumen fermentation and microbial yield in high producing lactating dairy cattle. Eight ruminally cannulated multiparous Holstein cows averaging (mean ± standard deviation) 60 ± 10 d in milk and 637 ± 38 kg of body weight were assigned to 1 of 2 treatment sequences in a switchback design. Treatment diets contained (dry matter basis) 44% corn silage, 13% alfalfa silage, 12% ground corn, and 31% premix containing either a control mix of urea and wheat middlings (CON) or a commercial fermentation byproduct meal (Fermenten, Arm and Hammer Animal Nutrition, Princeton, NJ) at 3% diet inclusion rate (EXP). Diets were formulated to be isonitrogenous and isocaloric, with similar levels of neutral detergent fiber and starch. The trial consisted of three 28-d experimental periods, where each period consisted of 21 d of diet adaptation and 7 d of data and sample collection. Omasal nutrient flows were determined using a triple-marker technique and double-labeled 15N15N-urea. The EXP diet provided 18 g/d more nonammonia N versus the CON diet, representing 3.0% of total N intake. Energy-corrected milk yield (41.7 and 43.1 kg/d for CON and EXP, respectively), milk fat, and protein yield and content did not differ between treatments. Total dry matter intake was similar between treatments (25.5 and 26.4 kg/d for CON and EXP, respectively). Ammonia N concentration and pool size in the rumen was greater in cows fed the EXP diet. No differences were observed in rumen or total-tract dry matter, organic matter, or neutral detergent fiber digestibility. Ruminal degradation of feed N was 15% lower in cows fed EXP diets, resulting in differences in omasal N flows. Results demonstrated the fermentation byproduct meal had a sparing effect on degradable feed protein, but did not increase microbial N flow from the rumen.

Rumen digestion kinetics, microbial yield, and omasal flows of nonmicrobial, bacterial, and protozoal amino acids in lactating dairy cattle fed fermentation by-products or urea as a soluble nitrogen source.

The objective of this study was to evaluate the effect of a fermentation by-product on rumen function, microbial yield, and composition and flows of nutrients from the rumen in high-producing lactating dairy cattle. Eight ruminally cannulated multiparous Holstein cows averaging (mean ± standard deviation) 60 ± 10 d in milk and 637 ± 38 kg of body weight were randomly assigned to 1 of 2 treatment sequences in a switchback design. Treatment diets contained (dry matter basis) 44% corn silage, 13% alfalfa silage, 12% ground corn, and 31% protein premix, containing either a control mix of urea and wheat middlings (CON) or a commercial fermentation by-product meal (Fermenten, Arm and Hammer Animal Nutrition, Princeton, NJ) at 3% diet inclusion rate (EXP). The trial consisted of three 28-d experimental periods, where each period consisted of 21 d of diet adaptation and 7 d of data and sample collection. A triple-marker technique and double-labeled 15N15N-urea were used to were used to measure protozoal, bacterial, and nonmicrobial omasal flow of AA. Rumen pool sizes and omasal flows were used to determine digestion parameters, including fractional rates of carbohydrate digestion, microbial growth, and yield of microbial biomass per gram of degraded substrate. Fermentation by-product inclusion in EXP diets increased microbial N and amino acid N content in microbes relative to microbes from CON cows fed the urea control. Microbial AA profile did not differ between diets. Daily omasal flows of AA were increased in EXP cows as a result of decreased degradation of feed protein. The inclusion of the fermentation by-product increased nonmicrobial AA flow in cows fed EXP versus CON. Average protozoal contribution to microbial N flow was 16.8%, yet protozoa accounted for 21% of the microbial AA flow, with a range of 8 to 46% for individual AA. Cows in this study maintained an average rumen pool size of 320 g of microbial N, and bacterial and protozoal pools were estimated at 4 different theoretical levels of selective protozoa retention. Fractional growth rate of all microbes was estimated to be 0.069 h-1, with a yield of 0.44 g of microbial biomass per gram of carbohydrate degraded. Results indicated that fermentation by-product can increase omasal flow of AA while maintaining adequate rumen N available for microbial growth and protein synthesis. Simulations from a developmental version of the Cornell Net Carbohydrate and Protein System indicated strong agreement between predicted and observed values, with some areas key for improvement in AA flow and bacterial versus protozoal N partitioning.

Development of an in vitro method to determine rumen undigested aNDFom for use in feed evaluation.

A portion of the forage cell wall, defined as neutral detergent fiber (NDF), is indigestible to anaerobic microbial digestion in ruminants. This fraction has been characterized by surface area relationships between acid detergent lignin, but recently, data have been published describing the dynamic nature of this relationship. In situ approaches have been described to estimate indigestible NDF, recovering the undigested NDF after long-term fermentations (uNDF). To be applicable to nutritionists and diet formulation, determining uNDF needs to be conducted in a commercial laboratory similar to other routine analyses of forage chemistry. A series of studies were conducted to evaluate an in vitro approach, to describe uNDF, which is repeatable and adaptable for routine feed evaluation. One hundred and two forages of several species were analyzed for NDF, acid detergent lignin, and uNDF. The uNDF was estimated by several approaches involving long-term fermentations and filtration steps to evaluate the length of time necessary to exhaust the digestible NDF and a filtration method necessary to maintain sample integrity by ensuring low sample loss and uniform recovery with residues from long-term in vitro fermentation. To determine uNDF, in vitro fermentations were conducted on 0.50 or 0.75 g of dry matter samples, in triplicate, at multiple time points up to 504 h and initially used Gooch crucibles with Celite (Thermo Fisher Scientific, Waltham, MA) as a filtering aid. The final method utilized a 1.5-µm pore size glass microfiber filter, which allowed for increased repeatability and improved sample recovery (lowest standard deviation). In this study, in vitro fermentations of 240 h were adequate to characterize and identify uNDF, which was repeatable among conventional forages provided the samples, after NDF analyses, were filtered through the same glass fiber filter. This approach could be adapted by commercial laboratories and would provide opportunities to develop near-infrared reflectance spectroscopy equations and calibrations.

Ruminal bacteria and protozoa composition, digestibility, and amino acid profile determined by multiple hydrolysis times.

Microbial samples from 4 independent experiments in lactating dairy cattle were obtained and analyzed for nutrient composition, AA digestibility, and AA profile after multiple hydrolysis times ranging from 2 to 168 h. Similar bacterial and protozoal isolation techniques were used for all isolations. Omasal bacteria and protozoa samples were analyzed for AA digestibility using a new in vitro technique. Multiple time point hydrolysis and least squares nonlinear regression were used to determine the AA content of omasal bacteria and protozoa, and equivalency comparisons were made against single time point hydrolysis. Formalin was used in 1 experiment, which negatively affected AA digestibility and likely limited the complete release of AA during acid hydrolysis. The mean AA digestibility was 87.8 and 81.6% for non-formalin-treated bacteria and protozoa, respectively. Preservation of microbe samples in formalin likely decreased recovery of several individual AA. Results from the multiple time point hydrolysis indicated that Ile, Val, and Met hydrolyzed at a slower rate compared with other essential AA. Singe time point hydrolysis was found to be nonequivalent to multiple time point hydrolysis when considering biologically important changes in estimated microbial AA profiles. Several AA, including Met, Ile, and Val, were underpredicted using AA determination after a single 24-h hydrolysis. Models for predicting postruminal supply of AA might need to consider potential bias present in postruminal AA flow literature when AA determinations are performed after single time point hydrolysis and when using formalin as a preservative for microbial samples.

Factors influencing completion of multi-dose vaccine schedules in adolescents: a systematic review.

BACKGROUND: Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi-dose vaccine schedules by adolescents. METHODS: Ten online databases and four websites were searched (February 2014). Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9-19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. RESULTS: Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27% to over 90%. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. CONCLUSIONS: Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will be invaluable to future new vaccine introductions and the further development of an adolescent health platform. PROSPERO reg# CRD42014006765.

Updating the Cornell Net Carbohydrate and Protein System feed library and analyzing model sensitivity to feed inputs.

The Cornell Net Carbohydrate and Protein System (CNCPS) is a nutritional model that evaluates the environmental and nutritional resources available in an animal production system and enables the formulation of diets that closely match the predicted animal requirements. The model includes a library of approximately 800 different ingredients that provide the platform for describing the chemical composition of the diet to be formulated. Each feed in the feed library was evaluated against data from 2 commercial laboratories and updated when required to enable more precise predictions of dietary energy and protein supply. A multistep approach was developed to predict uncertain values using linear regression, matrix regression, and optimization. The approach provided an efficient and repeatable way of evaluating and refining the composition of a large number of different feeds against commercially generated data similar to that used by CNCPS users on a daily basis. The protein A fraction in the CNCPS, formerly classified as nonprotein nitrogen, was reclassified to ammonia for ease and availability of analysis and to provide a better prediction of the contribution of metabolizable protein from free AA and small peptides. Amino acid profiles were updated using contemporary data sets and now represent the profile of AA in the whole feed rather than the insoluble residue. Model sensitivity to variation in feed library inputs was investigated using Monte Carlo simulation. Results showed the prediction of metabolizable energy was most sensitive to variation in feed chemistry and fractionation, whereas predictions of metabolizable protein were most sensitive to variation in digestion rates. Regular laboratory analysis of samples taken on-farm remains the recommended approach to characterizing the chemical components of feeds in a ration. However, updates to the CNCPS feed library provide a database of ingredients that are consistent with current feed chemistry information and laboratory methods and can be used as a platform to formulate rations and improve the description of biology within the model.

The Cornell Net Carbohydrate and Protein System: Updates to the model and evaluation of version 6.5.

New laboratory and animal sampling methods and data have been generated over the last 10 yr that had the potential to improve the predictions for energy, protein, and AA supply and requirements in the Cornell Net Carbohydrate and Protein System (CNCPS). The objectives of this study were to describe updates to the CNCPS and evaluate model performance against both literature and on-farm data. The changes to the feed library were significant and are reported in a separate manuscript. Degradation rates of protein and carbohydrate fractions were adjusted according to new fractionation schemes, and corresponding changes to equations used to calculate rumen outflows and postrumen digestion were presented. In response to the feed-library changes and an increased supply of essential AA because of updated contents of AA, a combined efficiency of use was adopted in place of separate calculations for maintenance and lactation to better represent the biology of the cow. Four different data sets were developed to evaluate Lys and Met requirements, rumen N balance, and milk yield predictions. In total 99 peer-reviewed studies with 389 treatments and 15 regional farms with 50 different diets were included. The broken-line model with plateau was used to identify the concentration of Lys and Met that maximizes milk protein yield and content. Results suggested concentrations of 7.00 and 2.60% of metabolizable protein (MP) for Lys and Met, respectively, for maximal protein yield and 6.77 and 2.85% of MP for Lys and Met, respectively, for maximal protein content. Updated AA concentrations were numerically higher for Lys and 11 to 18% higher for Met compared with CNCPS v6.0, and this is attributed to the increased content of Met and Lys in feeds that were previously incorrectly analyzed and described. The prediction of postruminal flows of N and milk yield were evaluated using the correlation coefficient from the BLUP (R(2)BLUP) procedure or model predictions (R(2)MDP) and the concordance correlation coefficient. The accuracy and precision of rumen-degradable N and undegradable N and bacterial N flows were improved with reduced bias. The CNCPS v6.5 predicted accurate and precise milk yield according to the first-limiting nutrient (MP or metabolizable energy) with a R(2)BLUP=0.97, R(2)MDP=0.78, and concordance correlation coefficient=0.83. Furthermore, MP-allowable milk was predicted with greater precision than metabolizable energy-allowable milk (R(2)MDP=0.82 and 0.76, respectively, for MP and metabolizable energy). Results suggest a significant improvement of the model, especially under conditions of MP limitation.

Sexual risk behavior, alcohol use, and social media use among secondary school students in informal settlements in Cape Town and Port Elizabeth, South Africa.

South Africa's HIV prevalence among young people remains among the highest in the world. A cross-sectional study was carried out in 2012 to estimate prevalences of sexual risk behavior and hazardous alcohol use (HAU) (via the Alcohol Use Disorder Identification Test) as well as to investigate potential associations between these outcomes and social media use. In all, 4485 students (mean age 15.66 years, SD 1.39) at 46 secondary schools in informal settlements in Cape Town and Port Elizabeth completed mobile-phone-assisted, self-administered baseline questionnaires within a cluster-randomized trial. In all, 312 females (12.5 %) and 468 males (23.5 %) screened positive for HAU (AOR = 1.98, 95 % CI 1.69-2.34). 730 males (39.9 %) and 268 females (11.8 %) reported having had two or more partners in the last year (AOR = 3.46, 95 % CI 2.87-4.16). Among females, having a Facebook account was associated with reported multiple partnerships in the last year (AOR = 1.81, 95 % CI 1.19-2.74), age-disparate sex in the last year (AOR = 1.96, 95 % CI 1.16-3.32) and HAU (AOR = 1.97, 95 % CI 1.41-2.74). Using Mxit-a popular mobile instant messaging application-was associated with higher odds of reported multiple partnerships in the last year among both males (AOR = 1.70, 95 % CI 1.35-2.14) and females (AOR = 1.45, 95 % CI 1.07-1.96) and with HAU among both males (AOR = 1.47, 95 % CI 1.14-1.90) and females (AOR = 1.50, 95 % CI 1.18-1.90). Further longitudinal and qualitative research should explore in more depth the observed links between social media and risk behavior.

Urea-N recycling in lactating dairy cows fed diets with 2 different levels of dietary crude protein and starch with or without monensin.

Rumensin (monensin; Elanco Animal Health, Greenfield, IN) has been shown to reduce ammonia production and microbial populations in vitro; thus, it would be assumed to reduce ruminal ammonia production and subsequent urea production and consequently affect urea recycling. The objective of this experiment was to determine the effects of 2 levels of dietary crude protein (CP) and 2 levels of starch, with and without Rumensin on urea-N recycling in lactating dairy cattle. Twelve lactating Holstein dairy cows (107 ± 21 d in milk, 647 kg ± 37 kg of body weight) were fed diets characterized as having high (16.7%) or low (15.3%) CP with or without Rumensin, while dietary starch levels (23 vs. 29%) were varied between 2 feeding periods with at least 7d of adaptation between measurements. Cows assigned to high or low protein and to Rumensin or no Rumensin remained on those treatments to avoid carryover effects. The diets consisted of approximately 40% corn silage, 20% alfalfa hay, and 40% concentrate mix specific to the treatment diets, with 0.5 kg of wheat straw added to the high starch diets to enhance effective fiber intake. The diets were formulated using Cornell Net Carbohydrate and Protein System (version 6.1), and the low-protein diets were formulated to be deficient for rumen ammonia to create conditions that should enhance the demand for urea recycling. The high-protein diets were formulated to be positive for both rumen ammonia and metabolizable protein. Rumen fluid, urine, feces, and milk samples were collected before and after a 72-h continuous jugular infusion of (15)N(15)N-urea. Total urine and feces were collected during the urea infusions for N balance measurements. Milk yield and dry matter intake were improved in cows fed the higher level of dietary CP and by Rumensin. Ruminal ammonia and milk and plasma urea nitrogen concentrations corresponded to dietary CP concentration. As has been shown in vitro, Rumensin reduced rumen ammonia concentration by approximately 23% but did not affect urea entry rate or gastrointestinal entry rate. Urea entry rate averaged approximately 57% of total N intake for cattle with and without Rumensin, and gastrointestinal rate was similar at 43 and 42% of N intake for cattle fed and not fed Rumensin, respectively. The cattle fed the high-protein diet had a 25% increase in urea entry rate and no effect of starch level was observed for any recycling parameters. Contrary to our hypothesis, Rumensin did not alter urea production and recycling.

Did the Olympics need more drugs? a doctor's reflection on providing medical care during Op OLYMPICS.

This paper examines some of the medical problems arising from the successful deployment of Defence Medical Services personnel to Op OLYMPICS (mid-June 2012-September 2012). It does not aim to be all encompassing in its scope, but focuses on the most pressing issues affecting a junior military doctor's ability to work effectively under field conditions. This will entail a discussion about whether in a deployment such as Op OLYMPICS medical care should be based upon offering solely primary healthcare in medical centres or using Role 1 medical treatment facilities, which include primary healthcare and pre-hospital emergency care. The main recommendations arising from the deployment are: clinicians should deploy with a minimum of basic emergency drugs and equipment; a medical facility treating a large population at risk for a prolonged period should have a broad stock of medications available on site; and medical risk assessments must be performed on all Reservists during mobilisation.

Complementarity of spike- and rate-based dynamics of neural systems.

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other.

Effectiveness of sport-based HIV prevention interventions: a systematic review of the evidence.

Interest in sport as a tool for behavioral HIV prevention has grown substantially in the past decade. With dozens of organisations now using sport-based HIV prevention (SBHP) approaches and upcoming randomized controlled trials in South Africa and Zimbabwe, there is a pressing need to synthesize previous evaluation findings and identify gaps in existing research. A systematic review on the effectiveness of SBHP interventions was carried out, identifying both published and unpublished studies on SBHP interventions that measured effectiveness quantitatively. Study quality was scored using an adapted Newcastle-Ottawa Scale. Random-effects meta-analyses were carried out across studies for effects on six categories of HIV-related outcomes. The review identified 952 publications, 21 of which met inclusion criteria. No randomised controlled trials on SBHP interventions and no studies assessing biological outcomes were identified. Mean study quality score was 5.1 (SD 3.1) out of 20 points. Overall strong evidence was observed for positive effects on HIV-related knowledge (RR = 1.26, 95 % CI = 1.15-1.37), stigma (RR = 1.13, 95 % CI = 1.02-1.24), self-efficacy (RR = 1.22, 95 % CI = 1.02-1.41), reported communication (RR = 1.24, 95 % CI = 1.06-1.41), and reported recent condom use (RR = 1.29, 95 % CI = 1.00-1.59). Generally, the review found encouraging evidence for some short-term effects but relied predominantly on low-quality studies. More rigorous research on SBHP is needed to objectively assess effectiveness. Randomised controlled trials could play an important role in guiding policies, strategies, and funding related to SBHP.

A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) has been a associated with a deletion of 1.5 megabases of chromosome 17p. One of four biopsy proven HNPP families that we have studied did not possess this deletion. As the deleted DNA region includes the coding region for a peripheral myelin gene (PMP22), we used single strand conformation analysis to examine this gene for mutations in the non-deleted HNPP family. An abnormal fragment in exon 1 was identified, and sequencing revealed a two base pair deletion in all affected family members. The deletion results in a frame shift, providing strong evidence that this gene has an important role in the pathogenesis of the disease.

The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a DNA duplication at chromosome 17p11.2. In view of the point mutation in the gene for peripheral myelin protein pmp-22/gas-3 in Trembler mice, a murine model for CMT1A, we have analysed whether this gene is altered in CMT1A. Here we show that the human homologue of the murine pmp-22 gene is located within the CMT1A DNA duplication, which is a direct repeat and does not interrupt the coding region of PMP-22. Expression of PMP-22 in CMT1A fibroblasts is similar to expression in control fibroblasts. Increased gene dosage or altered PMP-22 expression in the peripheral nervous system are therefore possible mechanisms by which PMP-22 is involved in CMT1A.

Acute hepatitis A virus infections in British Gurkha soldiers.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections are endemic in most developing countries, including Nepal and Afghanistan, and may cause outbreaks in military personnel. Previously, more than 99% of new British Gurkha recruits were already immune to HAV because of prior infection, but this may be declining due to improved living conditions in their countries of origin. Acute HAV infections have occurred in Gurkha soldiers serving in Afghanistan, which made them unfit for duty for 2-3 months. In one case, early serological diagnosis was impeded by IgM results against both HAV and HEV that were caused by cross-reactivity or persistence from a previous infection. These cases have led to a policy change whereby all Gurkha recruits are now tested for previous HAV infection and if negative they are offered vaccination. Meanwhile, HEV infection remains a significant threat in Nepal and Afghanistan with low levels of background immunity and no commercially available vaccine.

Evidence for a short-lived resonance state in enzyme catalysis via rate-equation convolution.

At the cellular level, all biological function relies on enzymes to provide catalytic acceleration of essential biochemical processes driving cellular metabolism. The enzyme is presumed to lower the activation energy barrier separating reactants from products, but the precise mechanism remains unresolved. Here we examine the temperature dependence of the enzyme-catalyzed dissociation of p-nitrophenyl-α-D-glucopyranoside (pNPG), a chromogenic analog for maltose, isomaltose, and sucrose disaccharide sugars, into p-nitrophenol (pNP) and glucose (monosaccharide). The enzymes of interest are the wild type and mutant forms of glucosidase MalL produced by the probiotic bacterium Bacillus subtilis. The per-enzyme production rates k(T) for the pNPG→ glucose reaction all show a characteristic temperature profile with an Arrhenius-like (approximately exponential) slow acceleration at low temperatures, rising through a point of inflexion to reach a maximum, then turning over to decline steeply towards zero production at high temperatures. This asymmetric profile is found to be well fitted by convolving an exponential growth function f(T) with a Gaussian temperature distribution g(T) to produce an exponentially modified Gaussian function h(T). To give a physical interpretation of the convolution components, we make the temperature mapping Θ≡T_{ref}-T where T_{ref} marks the temperature at which a given mutant becomes fully denatured (unfolded) and therefore inactive, then convert the convolution components to probability density functions which obey the convolution theorem of statistics. Working in Θ space, we identify f(Θ) as the density function for an Arrhenius-like transition from ground-state A to metastable-state B, and g(Θ) as the Gaussian distribution of offset-temperature fluctuations for the metastable state. By mapping the standard thermodynamic relations for temperature and energy fluctuations to the enzyme frame of reference, we are able to derive an expression for the lifetime for the metastable B state. For the 15 enzyme experiments, we obtain a mean value 〈Δt〉≳(29.0±1.3)×10^{-15}s, in remarkably good agreement with the ∼30-fs estimate for the period of glycosidic bond oscillations extracted from published infrared spectroscopy. We suggest that the metastable B state provides a low-energy target that has the effect of lowering the activation energy barrier by presenting an alternative axis for the reaction coordinate.