Navigating Increasing Levels of Relational Complexity: Perceptual, Analogical, and System Mappings.
Relational thinking involves comparing abstract relationships between mental representations that vary in complexity; however, this complexity is rarely made explicit during everyday comparisons. This study explored how people naturally navigate relational complexity and interference using a novel relational match-to-sample (RMTS) task with both minimal and relationally directed instruction to observe changes in performance across three levels of relational complexity: perceptual, analogy, and system mappings. Individual working memory and relational abilities were examined to understand RMTS performance and susceptibility to interfering relational structures. Trials were presented without practice across four blocks, and participants received feedback after each attempt to guide learning. Experiment 1 instructed participants to select the target that best matched the sample, whereas Experiment 2 additionally directed participants' attention to same and different relations. Participants in Experiment 2 demonstrated improved performance when solving analogical mappings, suggesting that directing attention to relational characteristics affected behavior. Higher performing participants-those with above-chance performance on the final block of system mappings-solved more analogical RMTS problems and had greater visuospatial working memory, abstraction, verbal analogy, and scene analogy scores compared to lower performers. Lower performers were less dynamic in their performance across blocks and demonstrated negative relationships between analogy and system mapping accuracy, suggesting increased interference between these relational structures. Participant performance on RMTS problems did not change monotonically with relational complexity, suggesting that increases in relational complexity places nonlinear demands on working memory. We argue that competing relational information causes additional interference, especially in individuals with lower executive function abilities.


[Morphology of the species Hyphessobrycon, heterorhabdus group (Characiformes: Characidae) in Colombia].
Hyphessobrycon is the most numerous and morphologically complex genus of Characidae, and includes 18 species reported for Colombia, from which thirteen belong to the heterorhabdus-group different methods have been proposed for species identification within this genus. This study used these species to undertake a morphogeometric analysis by the Box Truss and Thin Plate Splin (TPS) methods; 13 homologous landmarks type I and three type II were used. The result of cluster analysis indicated that these species are represented by two big groups: robust and thin. The uniform and non uniform components, and the principal warps (WP) and partial warps (Wparc), described the shape changes related to body depth, involving relative displacements of the appendicular skeleton and the cephalic region. All species were characterized by allometric growth with the exception of Hyphessobrycon mavro, who presented an isometry between the landmarks 6-7. Two new measures are proposed for species discrimination in the group (snout-supraoccipital spine distance and supraoccipital spine-pelvic fin).


Learning from EEG error-related potentials in noninvasive brain-computer interfaces.
We describe error-related potentials generated while a human user monitors the performance of an external agent and discuss their use for a new type of brain-computer interaction. In this approach, single trial detection of error-related electroencephalography (EEG) potentials is used to infer the optimal agent behavior by decreasing the probability of agent decisions that elicited such potentials. Contrasting with traditional approaches, the user acts as a critic of an external autonomous system instead of continuously generating control commands. This sets a cognitive monitoring loop where the human directly provides information about the overall system performance that, in turn, can be used for its improvement. We show that it is possible to recognize erroneous and correct agent decisions from EEG (average recognition rates of 75.8% and 63.2%, respectively), and that the elicited signals are stable over long periods of time (from 50 to > 600 days). Moreover, these performances allow to infer the optimal behavior of a simple agent in a brain-computer interaction paradigm after a few trials.


Mercury Contamination in Diamondback Terrapins in New Jersey.
Mercury contamination in consumed foods poses a significant threat to human health globally. The consumption of mercury-contaminated turtle meat is of special concern due to mercury's capability to bioaccumulate and biomagnify in organisms. Turtles are long-lived predators, allowing for a high degree of bioaccumulation and biomagnification of contaminants. In the U.S., diamondback terrapins (Malaclemys terrapin) are legally harvested in several states throughout their range. Harvested turtles are usually sold to both local and global markets mainly for human consumption, which results in a human consumption threat. The objective of this study was to analyze mercury concentrations to determine if the consumption of terrapins poses a threat to human health. Diamondback terrapins were collected from two study sites: Cape May and Hackensack Meadowlands, New Jersey, relatively pristine and contaminated estuaries, respectively. Turtle carapace, blood, and muscle samples were analyzed for total mercury concentrations. Results showed significant difference between study sites and females' and males' blood mercury concentrations. Similarly, results showed blood mercury correlated with carapace length. Results also showed that 50% of Cape May muscle samples and 72.7% Meadowlands muscles samples surpassed the New Jersey sensitive threshold of 0.18 ppm. Furthermore, 27.3% of Cape May muscle samples and 45.5% of Meadowlands muscles samples surpassed the U.S. Environmental Protection Agency's mercury threshold of 0.3 ppm for seafood consumption for the general public. Overall, the harvest of terrapins could pose a threat to consumers, and terrapins should be monitored closely or possibly banned for human consumption, especially in areas with known contamination history.


Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder.
Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response.


Free-time and fixed end-point optimal control theory in quantum mechanics: application to entanglement generation.
We have constructed free-time and fixed end-point optimal control theory for quantum systems and applied it to entanglement generation between rotational modes of two polar molecules coupled by dipole-dipole interaction. The motivation of the present work is to solve optimal control problems more flexibly by extending the popular fixed time and fixed end-point optimal control theory for quantum systems to free-time and fixed end-point optimal control theory. As a demonstration, the theory that we have constructed in this paper will be applied to entanglement generation in rotational modes of NaCl-NaBr polar molecular systems that are sensitive to the strength of entangling interactions. Our method will significantly be useful for the quantum control of nonlocal interaction such as entangling interaction, which depends crucially on the strength of the interaction or the distance between the two molecules, and other general quantum dynamics, chemical reactions, and so on.


Medication chart intervention improves inpatient thromboembolism prophylaxis.
Inpatient VTE prophylaxis is underused. This study evaluated the effectiveness of the low-cost, multifaceted Australian National Inpatient Medication Chart (NIMC) intervention on improving the quality of VTE prophylaxis and reducing disease. The NIMC intervention incorporated (1) a VTE risk stratification and appropriate prophylaxis guidance tool, (2) a prophylaxis contraindication screening instrument, and (3) a prophylaxis prescription prompt. Retrospective analysis of 2,371 consecutive medical and surgical admissions was performed at a regional referral hospital over 1 year both before and after the intervention. Outcomes measured included the frequency of prophylaxis use, timing of prophylaxis initiation, adherence of the prescribed prophylaxis regimen to guidelines, incidence of VTE disease, and prophylaxis-related complications. Following NIMC intervention, prophylaxis use increased from 52.7% to 66.5% in medical patients and from 77.5% to 89.1% in surgical patients (P < .001). This increase was still evident 12 months postintervention. After intervention, prophylaxis initiated on admission increased from 65.0% to 83.6% in medical patients and from 60.7% to 78.0% in surgical patients (P < .01); adherence rates to recommended guidelines increased from 55.6% to 71.0% in medical patients and from 53.6% to 75.6% in surgical patients (P < .01). More VTE risk factors independently triggered prophylaxis usage postintervention. The improved quality of prophylaxis did not significantly reduce VTE incidence (risk ratio, 0.88; 95% CI, 0.48-1.62). The rate of prophylaxis-related complications remained similar before and after intervention. The multifaceted NIMC intervention resulted in a sustained increase in appropriate and timely VTE prophylaxis in medical and surgical inpatients.


Changing behavioral risk for pregnancy among high school students in the United States, 1991-2007.
After dramatic declines in teen births and pregnancies from 1991 to 2005, teen birth rates in the United States increased in 2006 and 2007. We examined behavioral determinants of these trends and the likely direction of future trends. Pregnancy risk was estimated based on recent sexual activity, method of contraception used, and method-specific contraceptive efficacy, using data from young women on the national Youth Risk Behavior Survey (N approximately 125,000). Weighted logistic and linear regression were used to test for linear and quadratic (curved) trends over time. Between 1991 and 2007, behavioral risk for pregnancy declined, with all of the decline occurring between 1991 and 2003. Improvements in contraceptive use from 1991 to 2003 were found in condom use, nonuse, and use of withdrawal. Recent sexual activity (past 3 months) was unchanged over the entire period, except among black students. Quadratic changes were found in pregnancy risk for black teens and in condom use among all teens and black teens, suggesting that trends had reversed or flattened out. Although no change was found for any behavior between 2003 and 2007, pregnancy risk among sexually active teens demonstrated a borderline increase (p=.06) and small nonsignificant declines were seen for specific contraceptive methods. Pregnancy risk estimated from behavioral data correlated well with actual changes in teen pregnancy rates (1991-2004) and birth rates (1991-2006). After improvement in the 1990s and early 2000s, trends in behavioral risk for pregnancy appear to have stalled or even reversed among certain groups since 2003. These behavioral trends are consistent with the 2006 and 2007 increases in the teen birth rate. They may well portend further increases in 2008.


Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55).
A coxsackievirus B3 (CB3) isolate adapted to growth in RD cells shows an alteration in cell tropism as a result of its capacity to bind a 70-kDa cell surface molecule expressed on these cells. We now show that this molecule is the complement regulatory protein, decay-accelerating factor (DAF) (CD55). Anti-DAF antibodies prevented CB3 attachment to the cell surface. Radiolabeled CB3 adapted to growth in RD cells bound to CHO cells transfected with human DAF, whereas CB3 (strain Nancy), the parental strain, did not bind to DAF transfectants. These results indicate that growth of CB3 in RD cells selected for a virus strain that uses DAF for cell surface attachment.


Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1.
Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1-BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination.


Expression and inducibility of aryl hydrocarbon receptor pathway genes in wild-caught killifish (Fundulus heteroclitus) with different contaminant-exposure histories.
Wildcaught killifish from a contaminated site on the Elizabeth River (VA, USA) are refractory to induction of cytochrome P4501A (CYP1A, measured as catalytic activity and immunodetectable CYP1A protein) after exposure to typical aryl hydrocarbon receptor (AHR) agonists, as has been reported for fish from other sites highly contaminated with these compounds. In an attempt to understand the molecular basis for the lack of inducibility of CYP1A protein expression and activity in Elizabeth River killifish, we analyzed the expression of CYP1A and four other members of the AHR signal transduction pathway: AHR1, AHR2, AHR repressor (AHRR), and AHR nuclear translocator (ARNT). Gene expression was measured by cycle-optimized reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of messenger ribonucleic acid (mRNA) extracted from livers of killifish from the Elizabeth River and King's Creek (VA, USA) (reference site), 36 h after injection with beta-naphthoflavone (BNF, an AHR agonist) or corn oil (carrier control). Hepatic CYP1A mRNA was inducible in King's Creek killifish. However, in Elizabeth River killifish, no induction of CYP1A mRNA was observed, confirming and extending previous results showing no induction of CYP1A protein or catalytic activity in this population. Similarly, AHRR and AHR2 mRNA levels were induced by BNF in King's Creek but not Elizabeth River killifish. No population or treatment-related differences were observed in expression of AHR1 or ARNT mRNAs. The results reveal in Elizabeth River killifish a consistent lack of inducibility of genes that are normally inducible by AHR agonists (CYP1A, AHRR, AHR2). However, the expression of AHR1, AHR2, and AHRR in vehicle-treated fish did not differ between Elizabeth River and King's Creek killifish, suggesting that altered constitutive expression of AHRs or AHRR does not underlie the refractory CYP1A phenotype in Elizabeth River killifish.


The effect of tooth preparation height and diameter on the resistance of complete crowns to fatigue loading.
This study investigated the relationship between tooth preparation height and diameter and the resistance of cemented crowns to dynamic loading. Crown and abutment analogs were cemented using zinc oxide-eugenol, zinc phosphate, glass-ionomer, and resin composite luting agents. Abutment height varied from 1 to 7 mm in increments of 1 mm. Diameters of 3, 4, 5, 6, 7, and 8 mm were tested. A testing apparatus designed to apply dynamic stresses was used. The cemented crowns were loaded until the cement bond failed or the components reached 1 million stress cycles. The staircase technique was applied for data analysis. The results showed that: (1) the relationship between abutment height (or diameter) and resistance to dynamic lateral loading is approximately linear; and (2) crowns luted using resin composite cement were more resistant than those placed using glass-ionomer cement, which in turn were more resistant than crowns cemented with zinc phosphate or zinc oxide-eugenol cements.


Epidemiology of work-related injuries among insured construction workers in Iran.
Work-related injuries are among the most important health problems in developing countries, such as Iran. The purpose of this study was to determine the epidemiology of work-related injuries among construction workers who had been insured by the Iranian Social Security Organization (ISSO). This is a cross-sectional study. The population included all construction workers who had a work- related accident during 2012 in Iran, which were recorded in the ISSO database after inspection. The effects of independent variables on injuries were estimated by logistic regression. SPSS software version 18 was used for analyzing the data. Overall, 5352 work-related injuries were investigated. The incidence rate of fatal and nonfatal injuries was 0.07 in 1000 and 11.18 in 1000 workers, respectively. More than half of these accidents were due to careless activities. A younger age at the time of the accident (OR=0.98, CI: 0.97-0.99, p=0.001), being married (OR=1.37, CI: 1.04-1.79, p=0.02), place of accident (OR=1.86, CI: 1.18-2.92, p=0.007), lack of information (OR=5.28, CI: 1.57-17.75, p=0.007), disrespect of safety regulations (OR=3.11, CI: 1.87-5.17, p=0.001), non-use of protective equipment (OR=2.98, CI: 1.62-5.50, p=0.001), and defective equipment (OR=2.22, CI: 1.18-4.20, p=0.01) had a significant effect on the incidence of work-related injury. The pattern of work-related injury in Iran was almost similar in regard to age, gender, cause and type of the accident, with other parts of the world.


Difficult intravenous access tool in patients receiving peripheral chemotherapy: A pilot-validation study.
to develop a tool for measuring the difficulty of intravenous line insertion in cancer patients (DIVA-CP) receiving peripheral chemotherapy. a pilot-validation study divided into two phases was performed in a north-eastern Italian outpatient chemotherapy centre. In the first phase, a review of the literature and brainstorming sessions/direct discussions among expert oncology nurses were used to develop items on the DIVA-CP tool, and a panel of expert oncology nurses assessed the tool face and content validity. In the second phase, 260 adult patients undergoing single chemotherapy cycles were consecutively enrolled. Data was analysed for construct validity (explorative factor analysis) and inter-rater reliability (Cohen's Kappa). a 10-item tool was developed with four factors that were identified through factor analysis, explaining a total variance of 61.578%: accessibility to first choice veins (23.057%), venous fragility (15.197%), probable difficulties during the procedure (12.642%), and repeated exposure (10.691%). The tool demonstrated excellent inter-rater reliability (κ > 0.61 for 7 out of 10 items). the DIVA-CP tool is still a pilot instrument that needs to be improved through future studies. The tool has great potential and may perform an important role in oncological settings, allowing for easier venous assessment of patients receiving peripheral chemotherapy who are at risk of difficult intravenous access insertion. In addition, this instrument may help nurses to identify patients that may benefit from a central catheter promptly.


Changing perceptions of hunger on a high nutrient density diet.
People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet. This was a descriptive study conducted with 768 participants primarily living in the United States who had changed their dietary habits from a low micronutrient to a high micronutrient diet. Participants completed a survey rating various dimensions of hunger (physical symptoms, emotional symptoms, and location) when on their previous usual diet versus the high micronutrient density diet. Statistical analysis was conducted using non-parametric tests. Highly significant differences were found between the two diets in relation to all physical and emotional symptoms as well as the location of hunger. Hunger was not an unpleasant experience while on the high nutrient density diet, was well tolerated and occurred with less frequency even when meals were skipped. Nearly 80% of respondents reported that their experience of hunger had changed since starting the high nutrient density diet, with 51% reporting a dramatic or complete change in their experience of hunger. A high micronutrient density diet mitigates the unpleasant aspects of the experience of hunger even though it is lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. A high nutrient density diet provides benefits for long-term health as well as weight loss. Because our findings have important implications in the global effort to control rates of obesity and related chronic diseases, further studies are needed to confirm these preliminary results.


Hormone therapy for preventing cardiovascular disease in post-menopausal women.
Evidence from systematic reviews of observational studies suggests that hormone therapy may have beneficial effects in reducing the incidence of cardiovascular disease events in post-menopausal women, however the results of randomised controlled trials (RCTs) have had mixed results. This is an updated version of a Cochrane review published in 2013. To assess the effects of hormone therapy for the prevention of cardiovascular disease in post-menopausal women, and whether there are differential effects between use in primary or secondary prevention. Secondary aims were to undertake exploratory analyses to (i) assess the impact of time since menopause that treatment was commenced (≥ 10 years versus < 10 years), and where these data were not available, use age of trial participants at baseline as a proxy (≥ 60 years of age versus < 60 years of age); and (ii) assess the effects of length of time on treatment. We searched the following databases on 25 February 2014: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and LILACS. We also searched research and trials registers, and conducted reference checking of relevant studies and related systematic reviews to identify additional studies. RCTs of women comparing orally administered hormone therapy with placebo or a no treatment control, with a minimum of six months follow-up. Two authors independently assessed study quality and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for each outcome. We combined results using random effects meta-analyses, and undertook further analyses to assess the effects of treatment as primary or secondary prevention, and whether treatment was commenced more than or less than 10 years after menopause. We identified six new trials through this update. Therefore the review includes 19 trials with a total of 40,410 post-menopausal women. On the whole, study quality was good and generally at low risk of bias; the findings are dominated by the three largest trials. We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularisation. However, there was an increased risk of stroke in those in the hormone therapy arm for combined primary and secondary prevention (RR 1.24, 95% CI 1.10 to 1.41). Venous thromboembolic events were increased (RR 1.92, 95% CI 1.36 to 2.69), as were pulmonary emboli (RR 1.81, 95% CI 1.32 to 2.48) on hormone therapy relative to placebo.The absolute risk increase for stroke was 6 per 1000 women (number needed to treat for an additional harmful outcome (NNTH) = 165; mean length of follow-up: 4.21 years (range: 2.0 to 7.1)); for venous thromboembolism 8 per 1000 women (NNTH = 118; mean length of follow-up: 5.95 years (range: 1.0 to 7.1)); and for pulmonary embolism 4 per 1000 (NNTH = 242; mean length of follow-up: 3.13 years (range: 1.0 to 7.1)).We performed subgroup analyses according to when treatment was started in relation to the menopause. Those who started hormone therapy less than 10 years after the menopause had lower mortality (RR 0.70, 95% CI 0.52 to 0.95, moderate quality evidence) and coronary heart disease (composite of death from cardiovascular causes and non-fatal myocardial infarction) (RR 0.52, 95% CI 0.29 to 0.96; moderate quality evidence), though they were still at increased risk of venous thromboembolism (RR 1.74, 95% CI 1.11 to 2.73, high quality evidence) compared to placebo or no treatment. There was no strong evidence of effect on risk of stroke in this group. In those who started treatment more than 10 years after the menopause there was high quality evidence that it had little effect on death or coronary heart disease between groups but there was an increased risk of stroke (RR 1.21, 95% CI 1.06 to 1.38, high quality evidence) and venous thromboembolism (RR 1.96, 95% CI 1.37 to 2.80, high quality evidence). Our review findings provide strong evidence that treatment with hormone therapy in post-menopausal women overall, for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events.


Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review.
To determine the accuracy of magnetic resonance imaging criteria for the early diagnosis of multiple sclerosis in patients with suspected disease. Systematic review. 12 electronic databases, citation searches, and reference lists of included studies. Review methods Studies on accuracy of diagnosis that compared magnetic resonance imaging, or diagnostic criteria incorporating such imaging, to a reference standard for the diagnosis of multiple sclerosis. 29 studies (18 cohort studies, 11 other designs) were included. On average, studies of other designs (mainly diagnostic case-control studies) produced higher estimated diagnostic odds ratios than did cohort studies. Among 15 studies of higher methodological quality (cohort design, clinical follow-up as reference standard), those with longer follow-up produced higher estimates of specificity and lower estimates of sensitivity. Only two such studies followed patients for more than 10 years. Even in the presence of many lesions (> 10 or > 8), magnetic resonance imaging could not accurately rule multiple sclerosis in (likelihood ratio of a positive test result 3.0 and 2.0, respectively). Similarly, the absence of lesions was of limited utility in ruling out a diagnosis of multiple sclerosis (likelihood ratio of a negative test result 0.1 and 0.5). Many evaluations of the accuracy of magnetic resonance imaging for the early detection of multiple sclerosis have produced inflated estimates of test performance owing to methodological weaknesses. Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack of neurological dysfunction may lead to over-diagnosis and over-treatment.


Disentangling the intersection of inequities with health and malaria exposure: key lessons from rural communities in Northern Borneo.
The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members' perspectives regarding inequities to health relating to P. knowlesi malaria exposure. From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control.


Biochemical and biomechanical gradients for directed bone marrow stromal cell differentiation toward tendon and bone.
Substrates with mechanical property gradients and various extracellular matrix ligand loadings were evaluated for their ability to direct bone marrow stromal cell differentiation along osteogenic and tenogenic lineages. After verifying reproducible mechanical compliance characteristics of commercial hydrogel gradient substrates, substrates were functionalized with whole length fibronectin or collagen, both of which are found in skeletal structures and are relevant to cell-matrix signalling. Bone marrow stromal cells were seeded onto the substrates in growth media and cultured first to examine cell attachment and morphology, indicating higher levels of attachment on collagen substrates after 1h, and increased spreading and organization trends after 24h. Differentiation studies showed an increase in osteoblast differentiation on fibronectin substrates while collagen substrates lacked osteogenic differentiation. Osteogenic differentiation decreased on substrates of lower stiffness and lower ligand density. Molecular investigations revealed an increase in relevant signalling molecules for osteoblasts that were consistent with differentiation studies, but detected the presence of tenoblast markers on collagen substrates within a narrow range of stiffness. Our results indicate that mechanovariant substrates do hold promise as a culture platform for directed differentiation to tendon and bone by altering gene level expression of relevant signalling molecules. This study aids in understanding the molecular mechanisms that drive differentiation from substrate based cues, and could aid the design of therapeutic biomaterials at the transition from tendon to bone.


Frequent microbiological profile changes are seen in subsequent-revision hip and knee arthroplasty for prosthetic joint infection.
A proportion of patients with hip and knee prosthetic joint infection (PJI) undergo multiple revisions with the aim of eradicating infection and improving quality of life. The aim of this study was to describe the microbiology cultured from multiply revised hip and knee replacement procedures to guide antimicrobial therapy at the time of surgery. Patients and methods: Consecutive patients were retrospectively identified from databases at two specialist orthopaedic centres in the United Kingdom between 2011 and 2019. Patient were included who had undergone repeat-revision total knee replacement (TKR) or total hip replacement (THR) for infection, following an initial failed revision for infection. Results: A total of 106 patients were identified. Of these patients, 74 underwent revision TKR and 32 underwent revision THR. The mean age at first revision was 67 years (SD 10). The Charlson comorbidity index was ≤ 2 for 31 patients, 3-4 for 57 patients, and ≥ 5 for 18 patients. All patients underwent at least two revisions, 73 patients received three, 47 patients received four, 31 patients received five, and 21 patients received at least six. After six revisions, 90 % of patients had different organisms cultured compared with the initial revision, and 53 % of organisms were multidrug resistant. The most frequent organisms at each revision were coagulase-negative Staphylococcus (36 %) and Staphylococcus aureus (19 %). Fungus was cultured from 3 % of revisions, and 21 % of infections were polymicrobial. Conclusion: Patients undergoing multiple revisions for PJI are highly likely to experience a change in organism, with 90 % of patients having a different organism cultured by their sixth revision. It is therefore important to administer empirical antibiotics at each subsequent revision, taking into account known drug resistance from previous cultures. Our results do not support the routine use of empirical antifungals.


Saccadometry: a new tool for evaluating presymptomatic Huntington patients.
Saccadic reaction time or latency reflects the operation of the largely cortical mechanisms that decide where to look. An unusual feature of latency is that it varies randomly from trial to trial. In the past, this variation has been regarded as a nuisance, but analysis of its statistical properties has turned out to provide much insight into the underlying cerebral decision mechanisms. Thanks to recent technological improvements, large number of data can be gathered quickly and noninvasively using miniature, portable devices, offering the possibility of using saccadometry as a biomarker to enhance the diagnosis and monitoring of neurological conditions. Here we show that this technique can robustly distinguish genetically identified presymptomatic and symptomatic Huntington's disease patients from age-matched controls, largely through an increase in the number of unusually early responses, which might reflect an impairment of the tonic suppression of the colliculus normally mediated by pathways through the basal ganglia.


A 3-gene panel improves the prediction of left ventricular dysfunction after acute myocardial infarction.
Identification of patients at risk of poor outcome after acute myocardial infarction (MI) would allow tailoring healthcare to each individual. However, lack of prognostication tools renders this task challenging. Previous investigations suggested that blood transcriptome analysis may inform about prognosis after MI. We aim to independently confirm the value of gene expression profiles in the blood to predict left ventricular (LV) dysfunction after MI. Five genes (LMNB1, MMP9, TGFBR1, LTBP4 and TNXB) selected from previous studies were measured in peripheral blood samples obtained at reperfusion in 449 MI patients. 79 patients had LV dysfunction as attested by an ejection fraction (EF) ≤40% at 4-month follow-up and 370 patients had a preserved LV function (EF>40%). LMNB1, MMP9 and TGFBR1 were up-regulated in patients with LV dysfunction and LTBP4 was down-regulated, as compared with patients with preserved LV function. The 5 genes were significant univariate predictors of LV dysfunction. In multivariable analyses adjusted with traditional risk factors and corrected for model overfitting, a panel of 3 genes - TNXB, TGFBR1 and LTBP4 - improved the prediction of a clinical model (p=0.00008) and provided a net reclassification index of 0.45 [0.23-0.69], p=0.0002 and an integrated discrimination improvement of 0.05 [0.02-0.09], p=0.001. Bootstrap internal validation confirmed the incremental predictive value of the 3-gene panel. A 3-gene panel can aid to predict LV dysfunction after MI. Further independent validation is required before considering these findings for molecular diagnostic assay development.


Hydrogen adsorption on functionalized nanoporous activated carbons.
There is considerable interest in hydrogen adsorption on carbon nanotubes and porous carbons as a method of storage for transport and related energy applications. This investigation has involved a systematic investigation of the role of functional groups and porous structure characteristics in determining the hydrogen adsorption characteristics of porous carbons. Suites of carbons were prepared with a wide range of nitrogen and oxygen contents and types of functional groups to investigate their effect on hydrogen adsorption. The porous structures of the carbons were characterized by nitrogen (77 K) and carbon dioxide (273 K) adsorption methods. Hydrogen adsorption isotherms were studied at 77 K and pressure up to 100 kPa. All the isotherms were Type I in the IUPAC classification scheme. Hydrogen isobars indicated that the adsorption of hydrogen is very temperature dependent with little or no hydrogen adsorption above 195 K. The isosteric enthalpies of adsorption at zero surface coverage were obtained using a virial equation, while the values at various surface coverages were obtained from the van't Hoff isochore. The values were in the range 3.9-5.2 kJ mol(-1) for the carbons studied. The thermodynamics of the adsorption process are discussed in relation to temperature limitations for hydrogen storage applications. The maximum amounts of hydrogen adsorbed correlated with the micropore volume obtained from extrapolation of the Dubinin-Radushkevich equation for carbon dioxide adsorption. Functional groups have a small detrimental effect on hydrogen adsorption, and this is related to decreased adsorbate-adsorbent and increased adsorbate-adsorbate interactions.


The diagnostic utility of behavioral checklists in identifying children with ADHD and children with working memory deficits.
The present study investigated whether children with ADHD and those with working memory impairments have a common behavioral profile in the classroom. Three teacher checklists were used: the Conners' teacher rating scale (CTRS), the behavior rating inventory of executive function (BRIEF), and the working memory rating scale. The Conners' continuous performance test (CPT) was also included to determine whether there is a correspondence between performance on this widely used cognitive measure of attention deficits and teacher ratings of classroom behavior. All three behavior scales, but not the CPT, were able to successfully discriminate children with ADHD and those with working memory deficits from typically-developing children. Both the CTRS and the BRIEF discriminated a significant proportion of the children with ADHD from those with working memory deficits, indicating that while both groups exhibit behavioral problems in the classroom, they are characterized by differential attention profiles. The children with ADHD were identified on the basis of oppositional and hyperactive behavior, while those with working memory deficits were more inattentive.


Structure of human peptidyl-prolyl cis-trans isomerase FKBP22 containing two EF-hand motifs.
The FK506-binding protein (FKBP) family consists of proteins with a variety of protein-protein interaction domains and versatile cellular functions. It is assumed that all members are peptidyl-prolyl cis-trans isomerases with the enzymatic function attributed to the FKBP domain. Six members of this family localize to the mammalian endoplasmic reticulum (ER). Four of them, FKBP22 (encoded by the FKBP14 gene), FKBP23 (FKBP7), FKBP60 (FKBP9), and FKBP65 (FKBP10), are unique among all FKBPs as they contain the EF-hand motifs. Little is known about the biological roles of these proteins, but emerging genetics studies are attracting great interest to the ER resident FKBPs, as mutations in genes encoding FKBP10 and FKBP14 were shown to cause a variety of matrix disorders. Although the structural organization of the FKBP-type domain as well as of the EF-hand motif has been known for a while, it is difficult to conclude how these structures are combined and how it affects the protein functionality. We have determined a unique 1.9 Å resolution crystal structure for human FKBP22, which can serve as a prototype for other EF hand-containing FKBPs. The EF-hand motifs of two FKBP22 molecules form a dimeric complex with an elongated and predominantly hydrophobic cavity that can potentially be occupied by an aliphatic ligand. The FKBP-type domains are separated by a cleft and their putative active sites can catalyze isomerazation of two bonds within a polypeptide chain in extended conformation. These structural results are of prime interest for understanding biological functions of ER resident FKBPs containing EF-hand motifs.


[Thoracic and cardiovascular surgery in Jehovah's Witness].
A Jehovah's Witness who requires thoracic and cardiovascular surgery represents a challenge to both the surgeon and the patient because of the patient's refusal to accept blood transfusion. We reported 15 cases of Jehovah's Witness patients from 43 to 80 years of age who underwent cardiac operations or thoracic vascular operations. There was 1 emergency operation case and 2 re-do operation cases. Erythropoietin and serum albumin injections were allowed to be used in some cases. The mean pre-operative haemoglobin level in these patients was 12.3 g/dl. The mean postoperative lowest haemoglobin level was 9.2 g/dl. The mean haemoglobin level at the point of leaving hospital was 11.4 g/dl. There were no postoperative complications and no operative deaths. We successfully performed the thoracic and cardiovascular operations on Jehovah's Witnesses, including emergency cases, safely without blood transfusion. The most important thing is a careful and safe operative technique which reduces perioperative bleeding as much as possible.


Copper-modified covalent triazine frameworks as non-noble-metal electrocatalysts for oxygen reduction.
The electrochemical oxygen reduction reaction (ORR) is an important cathode reaction of various types of fuel cells. The development of electrocatalysts composed only of abundant elements is a key goal because currently only platinum is a suitable catalyst for ORR. Herein, we synthesized copper-modified covalent triazine frameworks (CTF) hybridized with carbon nanoparticles (Cu-CTF/CPs) as efficient electrocatalysts for the ORR in neutral solutions. The ORR onset potential of the synthesized Cu-CTF/CP was 810 mV versus the reversible hydrogen electrode (RHE; pH 7), the highest reported value at neutral pH for synthetic Cu-based electrocatalysts. Cu-CTF/CP also displayed higher stability than a Cu-based molecular complex at neutral pH during the ORR, a property that was likely as a result of the covalently cross-linked structure of CTF. This work may provide a new platform for the synthesis of durable non-noble-metal electrocatalysts for various target reactions.


Improved light output from InGaN LEDs by laser-induced dumbbell-like air-voids.
We report inducing an array of dumbbell-like air-voids inside the sapphire substrate in InGaN-based light-emitting diodes (LEDs) to improve the light extraction from LED device by a picosecond (Ps) pulse laser. At an injection current of 100 mA, the light output power (LOP) of packaged LEDs with laser-induced air-voids can be improved by 24.7% compared with conventional LEDs. Far-field radiation pattern has verified that this great improvement in LOP is due to the light scattering occurred at the interface of sapphire/air-voids. Current-Voltage curves show that the laser processing of air-voids will not degrade the LED electrical properties. Furthermore, leakage current at a level of ~5 nA at -10V has demonstrated an enhancement in the LED electrical performance with laser-induced air-voids. Second focusing mechanism, which is originated in the local heating effect around the laser focus, has been proposed to explain the formation of dumbbell-like air-voids.


A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone and mycophenolate mofetil in primary adult liver transplantation: a single center report.
Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently approved immunosuppressants for prevention of rejection in liver transplantation (LTx). They have different modes of action and toxicity profiles, but the efficacy and safety of MMF in primary liver transplantation with TAC has not been determined. An Institutional Review Board-approved, open-label, single-center, prospective randomized trial was initiated to study the efficacy and toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of patients were started on the same doses of TAC and steroids. Patients randomized to T also received 1 gm MMF twice a day. Between August 1995 and May 1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T groups. All patients were followed until May 1998, with a mean follow-up of 33.8+/-9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4-year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and 87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival was 70% for D and 72.1% for T. Although the rate of acute rejection in the first 3 months was significantly lower for T than for D (28% for triple vs. 38.9% for double, P=0.03), the overall rate of rejection for T at the end of 1 year was not significantly lower than for the D (38.9% triple vs. 45.2% double). The median time to the first episode of rejection was 14 days for D versus 24 days for T (P=0.008). During the study period, 38 of 175 patients in D received MMF to control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the other hand, 103 patients in the T discontinued MMF for infection, myelosuppression, and/or gastrointestinal disturbances. The need for corticosteroids was less after 6 months for T and the perioperative need for dialysis was lower with use of MMF. This final report confirms similar patient survival and graft survival up to 4 years with a trend towards fewer episodes of rejection, lower need for steroids, and better perioperative renal function. However, the complex nature of LTx patients and their posttransplantation course prevents the routine application of MMF.


Feasibility of optical coherence tomography imaging to characterize renal neoplasms: limitations in resolution and depth of penetration.
What's known on the subject? and What does the study add? Optical coherence tomography has been used for the diagnosis of retinal disease and has been used experimentally for imaging of vascular plaques, gastrointestinal pathology, bladder cancer, prostate cancer, and recently to examine benign kidney microanatomy. It has not been previously used to image kidney cancer. This study presents the first data on the utility of OCT in the imaging for renal neoplasms. It found that OCT was most successful in distinguishing AML and TCC from normal parenchyma. OCT had more limited success at differentiating oncocytoma. Clear cell tumors and other renal cancer subtypes had a more heterogenous appearance, precluding reliable identification using OCT. The study shows that higher resolution versions of OCT, such as OCM, will be needed to allow optical coherence imaging to reach clinical utility in the assessment of renal neoplasms. • To determine the appearance of normal and neoplastic renal tissue when imaged with optical coherence tomography (OCT). • To preliminarily assess the feasibility of using OCT to differentiate normal and neoplastic renal tissue. • After radical or partial nephrectomy in 20 subjects, normal renal parenchyma and neoplastic tissue samples were obtained. • The tissue was evaluated with light microscopy and using a bench-top laboratory OCT system with a lateral resolution of 10 µm. • OCT images were compared with histological slides to evaluate the ability of OCT to differentiate renal neoplasms. • Pathological subtypes included eight clear-cell, three papillary and two chromophobe renal carcinomas; two oncocytomas; one angiomyolipoma (AML); two transitional cell carcinomas (TCCs); and one haematoma. • Using OCT, benign renal parenchyma showed recognizable glomeruli and tubules. • TCC had a distinctive appearance on OCT whereas AML showed a unique identifiable signature because of its fat content. Oncocytomas had a lobulated appearance, which appeared subtly different from renal carcinoma. • Renal carcinoma lacked recognizable anatomical elements and had a heterogeneous appearance making differentiation from normal parenchyma at times difficult. • Subtypes of renal cancer appeared to vary on OCT imaging although discrimination was unreliable. • OCT imaging for renal neoplasms was most successful in distinguishing AML and TCC from normal parenchyma and malignant tumours. Oncocytoma differed subtly from renal carcinoma, making distinction more challenging. • Clear-cell tumours and other renal carcinoma subtypes had a heterogeneous appearance on OCT, which precluded reliable differentiation from normal parenchyma and between renal carcinoma subtypes. • Higher resolution versions of optical coherence imaging, such as optical coherence microscopy, will be necessary to achieve clinical utility.


Evaluation of a stool antigen test using a mAb for native catalase for diagnosis of Helicobacter pylori infection in children and adults.
Non-invasive diagnosis of Helicobacter pylori infection is important not only for screening of infection but also for epidemiological studies. Stool antigen tests are non-invasive and are convenient to identify H. pylori infection, particularly in children. We evaluated the stool antigen test, which uses a mAb for native catalase of H. pylori developed in Japan. A total of 151 stool samples were collected from participants (52 children and 99 adults) of the Sasayama Cohort Study and stored between -30 and -80 °C. The stool antigen test used was Testmate pylori antigen (TPAg), and was performed according to the manufacturer's instructions. Furthermore, we conducted a quantitative real-time PCR test and compared the PCR results with those of the TPAg test. When compared with the results in real-time PCR, the sensitivity of TPAg was 89.5 % overall, 82.7 % for children and 92.4 % for adults, and the specificity was 100 %. The accuracy was 93.4 % overall, 90.4 % for children and 94.9 % for adults, and there was no significant difference in the accuracy of TPAg between children and adults. Five of 28 children (18 %) and five of 38 adults (13 %) were PCR positive with negative TPAg results. Four of five children with positive PCR and negative TPAg results were given a (13)C-urea breath test and all four children tested negative. No significant correlation was observed between the TPAg results and DNA numbers of H. pylori in faeces among children or adults. A stool antigen test (TPAg) using a mAb for native catalase is useful for diagnosis of H. pylori in children and adults. Additionally, this test has particularly high specificity.


Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs.
The objective of this study was to provide preliminary data describing the safety and effect of cannabidiol (CBD) for symptom relief of canine osteoarthritis-associated pain in a clinical setting using objective outcome measures. Twenty-three client-owned dogs with naturally occurring osteoarthritis of appendicular joints completed this prospective, double-blinded, crossover, placebo-controlled study. Baseline data were acquired for 4 wk, followed by random allocation to either placebo or CBD treatment for 6 wk, followed by 6 wk with the opposite treatment. Outcome measures included objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. There were no differences noted between groups at any time point for any of the recorded outcome measures. Adverse events associated with CBD administration included elevation in liver enzymes (n = 14) and vomiting (n = 2).


Requirements for superoxide-dependent tyrosine hydroperoxide formation in peptides.
Superoxide reacts rapidly with other radicals, but these reactions have received little attention in the context of oxidative stress. For tyrosyl radicals, reaction with superoxide is 3-fold faster than dimerization, and forms the addition product tyrosine hydroperoxide. We have explored structural requirements for hydroperoxide formation using tyrosine analogues and di- and tri-peptides. Superoxide and phenoxyl radicals were generated using xanthine oxidase, peroxidase and the respective tyrosine derivative, or by gamma-radiation. Peroxides were measured using FeSO4/Xylenol Orange. Tyrosine and tyramine formed stable hydroperoxides, but N-acetyltyrosine and p-hydroxyphenylacetic acid did not, demonstrating a requirement for a free amino group. Using [14C]tyrosine, the hydroperoxide and dityrosine were formed at a molar ratio of 1.8:1. Studies with pre-formed hydroperoxides, and measurements of substrate losses, indicated that, in the absence of a free amino group, reaction with superoxide resulted primarily in restitution of the parent compound. With dipeptides, hydroperoxides were formed only on N-terminal tyrosines. However, adjacent lysines promoted hydroperoxide formation, as did addition of free lysine or ethanolamine. Results are compatible with a mechanism [d'Alessandro, Bianchi, Fang, Jin, Schuchmann and von Sonntag (2000) J. Chem. Soc. Perkin Trans. II, 1862-1867] in which the phenoxyl radicals react initially with superoxide by addition, and the intermediate formed either releases oxygen to regenerate the parent compound or is converted into a hydroperoxide. Amino groups favour hydroperoxide formation through Michael addition to the tyrosyl ring. These studies indicate that tyrosyl hydroperoxides should be formed in proteins where there is a basic molecular environment. The contribution of these radical reactions to oxidative stress warrants further investigation.


Busy yet socially engaged: volunteering, work-life balance, and health in the working population.
To understand the relationship between volunteering and health in the overlooked yet highly engaged working population, adopting a contextualizing balance approach. We hypothesize that volunteering may function as a psychosocial resource, contributing to work-life balance and, ultimately, health. A total of 746 Swiss workers participated in an online survey; 35% (N = 264) were additionally volunteers in a nonprofit organization. We assessed volunteering, work-life balance perceptions, paid job demands, and resources and health outcomes. After controlling for job characteristics, volunteering was associated with less work-life conflict, burnout and stress, and better positive mental health. Results further revealed that balance perceptions partly explained the relationship between volunteering and health. Volunteering, albeit energy and time-consuming, may contribute to a greater sense of balance for people in the workforce, which might, in turn, positively influence health.


X-ray structures of human bile-salt activated lipase conjugated to nerve agents surrogates.
The efficiency of human butyrylcholinesterase (BChE) as a stoichiometric bioscavenger of nerve agents is well established. However, wide use is currently limited by production and purification costs. Aiming at identifying an alternative human protein bioscavenger, we looked for an original scaffold candidate by virtual screening of the Protein Data Bank for functional similarity using the "Surfing the Molecules" software (sumo-pbil.ibcp.fr) and a search model based on the BChE active site topology. Besides the expected acetylcholinesterase and butyrylcholinesterase, we identified a set of bile salt activated lipases structures, among which the human pancreatic lipase (hBAL) that shares 34% identity with BChE. We produced the recombinant enzyme in mammalian cells, purified it, and measured the inhibition constants for paraoxon and surrogates of VX, sarin and tabun. We solved the X-ray structure of apo hBAL and conjugates with paraoxon and the surrogates at resolutions in the 2-Å range. These structures allow the assessment of hBAL for scavenging nerve agents. They revealed that hBAL has inverted stereoselectivity for the surrogates of nerve agent compared to human cholinesterases. We observed a remarkable flip of the catalytic histidine driven by the chelation of Zn2+. Dealkylation of the conjugate, aka aging, was solely observed for paraoxon.


The 2016 World Health Organization Classification of tumours of the Central Nervous System: what the paediatric neuroradiologist needs to know.
The recently published 2016 World Health Organization (WHO) classification of tumours of the Central Nervous System (CNS) introduces a number of significant changes from the previous edition. Based on an improved understanding of the genetic and molecular basis of tumorigenesis there has been a shift towards defining tumours by means of these characteristics in addition to their histological features, thus providing an integrated diagnosis. In this article, we will provide a concise overview of the salient changes in the 2016 WHO classification of tumours of the CNS that are of relevance to the paediatric neuroradiologist when it comes to day-to-day reporting.


WINPEPI updated: computer programs for epidemiologists, and their teaching potential.
The WINPEPI computer programs for epidemiologists are designed for use in practice and research in the health field and as learning or teaching aids. The programs are free, and can be downloaded from the Internet. Numerous additions have been made in recent years. There are now seven WINPEPI programs: DESCRIBE, for use in descriptive epidemiology; COMPARE2, for use in comparisons of two independent groups or samples; PAIRSetc, for use in comparisons of paired and other matched observations; LOGISTIC, for logistic regression analysis; POISSON, for Poisson regression analysis; WHATIS, a "ready reckoner" utility program; and ETCETERA, for miscellaneous other procedures. The programs now contain 122 modules, each of which provides a number, sometimes a large number, of statistical procedures. The programs are accompanied by a Finder that indicates which modules are appropriate for different purposes. The manuals explain the uses, limitations and applicability of the procedures, and furnish formulae and references. WINPEPI is a handy resource for a wide variety of statistical routines used by epidemiologists. Because of its ready availability, portability, ease of use, and versatility, WINPEPI has a considerable potential as a learning and teaching aid, both with respect to practical procedures in the planning and analysis of epidemiological studies, and with respect to important epidemiological concepts. It can also be used as an aid in the teaching of general basic statistics.


Endocannabinoid-Mediated Neuromodulation in the Olfactory Bulb: Functional and Therapeutic Significance.
Endocannabinoid synthesis in the human body is naturally occurring and on-demand. It occurs in response to physiological and environmental stimuli, such as stress, anxiety, hunger, other factors negatively disrupting homeostasis, as well as the therapeutic use of the phytocannabinoid cannabidiol and recreational use of exogenous cannabis, which can lead to cannabis use disorder. Together with their specific receptors CB1R and CB2R, endocannabinoids are major components of endocannabinoid-mediated neuromodulation in a rapid and sustained manner. Extensive research on endocannabinoid function and expression includes studies in limbic system structures such as the hippocampus and amygdala. The wide distribution of endocannabinoids, their on-demand synthesis at widely different sites, their co-existence in specific regions of the body, their quantitative differences in tissue type, and different pathological conditions indicate their diverse biological functions that utilize specific and overlapping pathways in multiple organ systems. Here, we review emerging evidence of these pathways with a special emphasis on the role of endocannabinoids in decelerating neurodegenerative pathology through neural networks initiated by cells in the main olfactory bulb.


Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues.
We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions. In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation. A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.


Relationship between white blood cell count and components of metabolic syndrome among young adolescents.
Components of metabolic syndrome (MetS) have been associated with several inflammatory factors, including white blood cell count (WBCC). In the present study, the relationships between WBCC and aspects of MetS in young adolescents were investigated. We enrolled 596 participants (328 males and 268 females) from 10 to 13 years of age and with normal WBCC in this study. They were divided into four quartiles according to WBCC (WBCC1-4, from lowest to highest WBCC). The mean values of MetS components for each group were compared in males and females separately. Multivariate linear regression analysis between the WBCC and the components of MetS after adjusted for age and body mass index (BMI) were also evaluated. In the male group, the BMI of WBCC1 and WBCC2 was significantly lower than WBCC4. The total cholesterol and low-density lipoprotein-cholesterol (LDL-C) of WBCC2 were significantly higher than WBCC1 and WBCC4. Triglyceride (TG) levels of WBCC1 were significantly lower than WBCC3 and WBCC4, and TG levels of WBCC2 were significantly lower than WBCC4. Alternatively, the BMI of WBCC1 and WBCC2 were significantly lower than WBCC3 in the female group. Finally, the TG and fasting plasma glucose (FPG) levels of WBCC1 were significantly lower than WBCC3 or WBCC4, respectively. After multivariate linear regression, WBCC was positively correlated to BMI and TG, but negatively correlated to FPG in males whereas in young adolescent females, WBCC was positively correlated to BMI and FPG. In conclusion BMI was positively correlated with WBCC in young adolescent females and males. Thus, BMI is the most important component of MetS in this age group. In addition, TG levels in males and FPG in females were significantly related to WBCC. These findings could be regarded an early indication for the future development of full-blown MetS or cardiovascular diseases.


Estimating co-occurring behavioral trajectories within a neighborhood context: a case study of multivariate transition models for clustered data.
Comorbidity is well-documented in psychiatric and risk behavior epidemiology. The authors present a novel application of clustered multivariate transition models to study comorbidity within a clustered context. The authors used data from the Project on Human Development in Chicago Neighborhoods (1995-2002) to assess trajectories in substance use, problems with police, and antisocial behavior among 1,517 participants in 80 neighborhoods followed from ages 12-15 years through ages 18-21 years. The authors used pairwise odds ratios to quantify behavior comorbidity at the individual and neighborhood levels. Risk behaviors co-occurred within individuals at specific points in time: antisocial behavior and substance use were 3.37 times more likely to co-occur within an individual at wave 1, as compared with the co-occurrence of any 2 behaviors from different individuals, while substance use and police problems were 2.94 times more likely to co-occur than substance use and antisocial behavior at wave 2. The authors also evaluated sequential comorbidity. Antisocial behavior was sequentially comorbid with substance use and police problems: 31% of youths who had reported antisocial behavior at baseline reported police problems or drug use at wave 2. These models can prove instrumental in answering the persistent questions about possible sequential relations among problem behaviors.


Disaster preparedness for earthquakes in hemodialysis units in Gyeongju and Pohang, South Korea.
In 2016 and 2017, there were earthquakes greater than 5.0 in magnitude on the Korean Peninsula, which has previously been considered an earthquake-free zone. Patients with chronic kidney disease are particularly vulnerable to earthquakes, as the term "renal disaster" suggests. In the event of a major earthquake, patients on hemodialysis face the risk of losing maintenance dialysis due to infrastructure disruption. In this review, we share the experience of an earthquake in Pohang that posed a serious risk to patients on hemodialysis. We review the disaster response system in Japan and propose a disaster preparedness plan with respect to hemodialysis. Korean nephrologists and staff in dialysis facilities should be trained in emergency response to mitigate risk from natural disasters. Dialysis staff should be familiar with the action plan for natural disaster events that disrupt hemodialysis, such as outages and water treatment system failures caused by earthquakes. Patients on hemodialysis also need to be educated about disaster preparedness. In the event of a disaster situation that results in dialysis failure, patients need to know what to do. At the local and national government level, long-term preparations should be made to handle renal disaster and patient safety logistics. Moreover, Korean nephrologists should also be prepared to manage cardiovascular disease and diabetes in disaster situations. Further evaluation and management of social and national disaster preparedness of hemodialysis units to earthquakes in Korea are needed.


Darwin's Originality.
Charles Darwin's theory of natural selection has been hailed as one of the most innovative contributions to modern science. When first proposed in 1859, however, it was widely rejected by his contemporaries, even by those who accepted the general idea of evolution. This article identifies those aspects of Darwin's work that led him to develop this revolutionary theory, including his studies of biogeography and animal breeding, and his recognition of the role played by the struggle for existence.


The effect of late pregnancy consumption of date fruit on labour and delivery.
We set out to investigate the effect of date fruit (Phoenix dactylifera) consumption on labour parameters and delivery outcomes. Between 1 February 2007 and 31 January 2008 at Jordan University of Science and Technology, a prospective study was carried out on 69 women who consumed six date fruits per day for 4 weeks prior to their estimated date of delivery, compared with 45 women who consumed none. There was no significant difference in gestational age, age and parity between the two groups. The women who consumed date fruit had significantly higher mean cervical dilatation upon admission compared with the non-date fruit consumers (3.52 cm vs 2.02 cm, p < 0.0005), and a significantly higher proportion of intact membranes (83% vs 60%, p = 0.007). Spontaneous labour occurred in 96% of those who consumed dates, compared with 79% women in the non-date fruit consumers (p = 0.024). Use of prostin/oxytocin was significantly lower in women who consumed dates (28%), compared with the non-date fruit consumers (47%) (p = 0.036). The mean latent phase of the first stage of labour was shorter in women who consumed date fruit compared with the non-date fruit consumers (510 min vs 906 min, p = 0.044). It is concluded that the consumption of date fruit in the last 4 weeks before labour significantly reduced the need for induction and augmentation of labour, and produced a more favourable, but non-significant, delivery outcome. The results warrant a randomised controlled trial.


Use of diatom assemblages as biomonitor of the impact of treated uranium mining effluent discharge on a stream: case study of the Ritord watershed (Center-West France).
The rehabilitation of French former uranium mining sites has not prevented the contamination of the surrounding aquatic ecosystems with metal elements. This study assesses the impact of the discharge of treated uranium mining effluents on periphytic diatom communities to evaluate their potential of bioindication. A 7-month survey was conducted on the Ritord watercourse to measure the environmental conditions of microalgae, the non-taxonomic attributes of periphyton (photosynthesis and biomass) and to determine the specific composition of diatom assemblages grown on artificial substrates. The environmental conditions were altered by the mine waters, that contaminate the watercourse with uranium and with chemicals used in the pit-water treatment plants (BaCl2 and Al2(SO4)3). The biomass and photosynthetic activity of periphyton seemed not to respond to the stress induced by the treated mining effluents whereas the altered environmental conditions clearly impacted the composition of diatom communities. Downstream the discharges, the communities tended to be characterized by indicator species belonging to the genera Fragilaria, Eunotia and Brachysira and were highly similar to assemblages at acid mine drainage sites. The species Eunotia pectinalis var. undulata, Psammothidium rechtensis, Gomphonema lagenula and Pinnularia major were found to be sensitive to uranium effluents whereas Neidium alpinum and several species of Gomphonema tolerated this contamination. The relevance of diatoms as ecological indicator was illustrated through the changes in structure of communities induced by the discharge of uranium mining effluents and creates prospects for development of a bioindicator tool for this kind of impairment of water quality.


Transcriptional Regulation of the Astrocytic Excitatory Amino Acid Transporter 1 (EAAT1) via NF-κB and Yin Yang 1 (YY1).
Astrocytic glutamate transporter excitatory amino acid transporter (EAAT) 1, also known as glutamate aspartate transporter (GLAST) in rodents, is one of two glial glutamate transporters that are responsible for removing excess glutamate from synaptic clefts to prevent excitotoxic neuronal death. Despite its important role in neurophysiological functions, the molecular mechanisms of EAAT1 regulation at the transcriptional level remain to be established. Here, we report that NF-κB is a main positive transcription factor for EAAT1, supported by the following: 1) EAAT1 contains two consensus sites for NF-κB, 2) mutation of NF-κB binding sites decreased EAAT1 promoter activity, and 3) activation of NF-κB increased, whereas inhibition of NF-κB decreased EAAT1 promoter activity and mRNA/protein levels. EGF increased EAAT1 mRNA/protein levels and glutamate uptake via NF-κB. The transcription factor yin yang 1 (YY1) plays a role as a critical negative regulator of EAAT1, supported by the following: 1) the EAAT1 promoter contains multiple consensus sites for YY1, 2) overexpression of YY1 decreased EAAT1 promoter activity and mRNA/protein levels, and 3) knockdown of YY1 increased EAAT1 promoter activity and mRNA/protein levels. Manganese decreased EAAT1 expression via YY1. Epigenetic modifiers histone deacetylases (HDACs) served as co-repressors of YY1 to further decrease EAAT1 promoter activity, whereas inhibition of HDACs reversed manganese-induced decrease of EAAT1 expression. Taken together, our findings suggest that NF-κB is a critical positive regulator of EAAT1, mediating the stimulatory effects of EGF, whereas YY1 is a negative regulator of EAAT1 with HDACs as co-repressors, mediating the inhibitory effects of manganese on EAAT1 regulation.


Yeast community structures and dynamics in healthy and Botrytis-affected grape must fermentations.
Indigenous yeast population dynamics during the fermentation of healthy and Botrytis-affected grape juice samples from two regions in Greece, Attica and Arcadia, were surveyed. Species diversity was evaluated by using restriction fragment length polymorphism and sequence analyses of the 5.8S internal transcribed spacer and the D1/D2 ribosomal DNA (rDNA) regions of cultivable yeasts. Community-level profiles were also obtained by direct analysis of fermenting samples through denaturing gradient gel electrophoresis of 26S rDNA amplicons. Both approaches revealed structural divergences in yeast communities between samples of different sanitary states or geographical origins. In all cases, Botrytis infection severely perturbed the bioprocess of fermentation by dramatically altering species heterogeneity and succession during the time course. At the beginning and middle of fermentations, Botrytis-affected samples possessed higher levels of biodiversity than their healthy counterparts, being enriched with fermentative and/or spoilage species, such as Zygosaccharomyces bailii and Issatchenkia spp. or Kluyveromyces dobzhanskii and Kazachstania sp. populations that have not been reported before for wine fermentations. Importantly, Botrytis-affected samples exposed discrete final species dominance. Selection was not species specific, and two different populations, i.e., Saccharomyces cerevisiae in samples from Arcadia and Z. bailii in samples from Attica, could be recovered at the end of Botrytis-affected fermentations. The governing of wine fermentations by Z. bailii is reported for the first time and could elucidate the origins and role of this particular spoilage microbe for the wine industry. This is the first survey to compare healthy and Botrytis-affected spontaneous fermentations by using both culture-based and -independent molecular methods in an attempt to further illuminate the complex yeast ecology of grape must fermentations.


Role of the private sector in the provision of immunization services in low- and middle-income countries.
The authors conducted a literature review on the role of the private sector in low- and middle-income countries. The review indicated that relatively few studies have researched the role of the private sector in immunization service delivery in these countries. The studies suggest that the private sector is playing different roles and functions according to economic development levels, the governance structure and the general presence of the private sector in the health sector. In some countries, generally low-income countries, the private for-profit sector is contributing to immunization service delivery and helping to improve access to traditional EPI vaccines. In other countries, particularly middle-income countries, the private for-profit sector often acts to facilitate early adoption of new vaccines and technologies before introduction and generalization by the public sector. The not-for-profit sector plays an important role in extending access to traditional EPI vaccines, particularly in low-income countries. Not-for-profit facilities are situated in rural as well as urban areas and are more likely to be coordinated with public services than the private for-profit sector. Although numerous studies on non-governmental organizations (NGOs) suggest that the extent of NGO provision of immunization services in low- and middle-income countries is substantial, the contribution of this sector is poorly documented, leading to a lack of recognition of its role at national and global levels. Studies on quality of immunization service provision at private health facilities suggest that it is sometimes inadequate and needs to be monitored. Although some articles on public-private collaboration exist, little was found on the extent to which governments are effectively interacting with and regulating the private sector. The review revealed many geographical and thematic gaps in the literature on the role and regulation of the private sector in the delivery of immunization services in low- and middle-income countries.


Clinical utility of rapid prescreening magnetic resonance angiography of peripheral vascular disease prior to cardiac catheterization.
The presence of peripheral vascular disease, in particular iliofemoral disease, is responsible in part for vascular complications from femoral artery cannulation. We investigated whether prescreening for vascular obstructions with magnetic resonance angiography (MRA) in high-risk patients with peripheral vascular disease (PVD) would provide useful information to angiographers seeking to improve the safety and efficiency of femoral artery access at cardiac catheterization. Twelve consecutive patients with known or suspected PVD underwent contrast-enhanced, aorto-iliofemoral MRA using a real-time BolusTrak technique. Contrast-to-noise ratios for each patient were calculated. The cardiac angiographer reviewed the MRA prior to catheterization and selected an access site. The patients' subsequent clinical course was evaluated, and a postprocedure questionnaire was completed by the angiographer to define the value of the prescreening MRA. No significant vascular complications occurred in these patients as defined by failure of initially chosen access site, arterial dissection, limb ischemia, pseudoaneurysm formation, hemorrhage (including retroperitoneal hematoma), or need for blood transfusion or emergency vascular surgical repair. Statistical frequency analysis of the responses in the postprocedure questionnaire demonstrated that the MR data were clinically valuable in (1) influencing the initial choice of access site; (2) influencing technical alterations to the standard access; and, (3) enhancing confidence in the selection of access site. MRA prescreening in patients with PVD is an effective, novel adjunct to cardiac catheterization in selected patients that improves physician confidence and influences technical choices during coronary angiography from the femoral artery approach.


NMR measurements of scalar-coupling distributions in disordered solids.
The measurement of scalar (J) couplings by solid-state NMR is a field of great interest, since this interaction is a rich source of local structural information, complementary to dipolar and chemical shift interactions. Here, we first demonstrate that J-coupling distributions exist and can be observed in disordered solids, as illustrated with the observation of a pair-specific distribution of (2)J((31)P-N-(31)P) couplings in a bis-phosphino amine, and we investigate the potential effects of such distributions on the measurement of average J-coupling constants. Second, we show that the measurement of two-dimensional (2D) distributions of J-couplings provides a much richer probe of local structural disorder than one-dimensional distributions, and we introduce new methods that provide different (selective or non-selective) ways of measuring 2D J distributions in a wide range of disordered systems. These methods are finally applied to a slightly disordered polymorphic sample of fully (13)C-enriched cellulose, and then to the bis-phosphino amine sample, from which 2D (2)J(PP)-coupling distributions are clearly identified and interpreted.


Evaluation of new Cu(II) complexes as a novel class of inhibitors against plant carbonic anhydrase, glutathione reductase, and photosynthetic activity in photosystem II.
Increasing inefficiency of production of important agricultural plants raises one of the biggest problems in the modern world. Herbicide application is still the best method of weed management. Traditional herbicides blocking only one of the plant metabolic pathways is ineffective due to the rapid growth of herbicide-resistant weeds. The synthesis of novel compounds effectively suppressing several metabolic processes, and therefore achieving the synergism effect would serve as the alternative approach to weed problem. For this reason, recently, we synthesized a series of nine novel Cu(II) complexes and four ligands, characterized them with different analyses techniques, and carried out their primary evaluation as inhibitors of photosynthetic electron transfer in spinach thylakoids (design, synthesis, and evaluation of a series of Cu(II) based metal-organic complexes as possible inhibitors of photosynthesis, J Photochem Photobiol B, submitted). Here, we evaluated in vitro inhibitory potency of these agents against: photochemistry and carbonic anhydrase activity of photosystem II (PSII); α-carbonic anhydrase from bovine erythrocytes; as well as glutathione reductase from chloroplast and baker's yeast. Our results show that all Cu(II) complexes excellently inhibit glutathione reductase and PSII carbonic anhydrase activity. Some of them also decently inhibit PSII photosynthetic activity.


Syntaxin of plant proteins SYP123 and SYP132 mediate root hair tip growth in Arabidopsis thaliana.
Root hairs are fast-growing tubular protrusions on root epidermal cells that play important roles in water and nutrient uptake in plants. The tip-focused polarized growth of root hairs is accomplished by the secretion of newly synthesized materials to the tip via the polarized membrane trafficking mechanism. Here, we report the function of two different types of plasma membrane (PM) Qa-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), SYP123 and SYP132, in the growth of root hair in Arabidopsis. We found that SYP123, but not SYP132, localizes in the tip region of root hairs by recycling between the brefeldin A (BFA)-sensitive endosomes and the PM of the expanding tip in an F-actin-dependent manner. The vesicle-associated membrane proteins VAMP721/722/724 also exhibited tip-focused localization in root hairs and formed ternary SNARE complexes with both SYP123 and SYP132. These results demonstrate that SYP123 and SYP132 act in a coordinated fashion to mediate tip-focused membrane trafficking for root hair tip growth.


Prenatal exposure, maternal sensitization, and sensitization in utero to indoor allergens in an inner-city cohort.
Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 upregulation.


Integrated phytochemical analysis based on UHPLC-LTQ-Orbitrap and network pharmacology approaches to explore the potential mechanism of Lycium ruthenicum Murr. for ameliorating Alzheimer's disease.
Based on compelling experimental and clinical evidence, the fruit of Lycium ruthenicum Murr. (LRM), a unique traditional Tibetan medicine, exerts beneficial effects on ameliorating learning and memory deficits of Alzheimer's disease (AD) and other neurodegenerative disorders. However, the potential active constituents and biological mechanism of LRM are still unknown. In this study, the major chemical constituents of LRM were first analyzed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap). A total of 35 constituents were confirmed or tentatively identified. Furthermore, the network-based pharmacological strategy was applied to clarify the molecular mechanism of LRM on AD based on the identified components. Totally, 143 major targets were screened and supposed to be effective players in alleviating AD. Then, the LRM chemicals-major LRM putative targets-major pathways network was constructed, implying potential biological function of LRM on AD. More importantly, 12 core genes which can be modulated by LRM were identified, and they may play a pivotal role in alleviating some major symptoms of AD. This study provided a scientific basis for further investigation and application of LRM, which demonstrated that the network pharmacology approach could be a powerful way for the mechanistic studies of folk medicines.


The influence of space and time on the establishment of B cell identity.
During embryonic development multiple waves of hematopoietic progenitors with distinct lineage potential are differentially regulated in time and space. Consistent with this view, some specialized lymphocytes emerge during a limited time-window in embryogenesis and migrate to the tissues where they contribute to organogenesis and to tissue homeostasis. These cells are not constantly produced by bone marrow derived hematopoietic stem cells but are maintained in tissues and self-renew throughout life. These particular cell subsets are produced from lymphoid restricted progenitors only found in the first days of fetal liver hematopoietic activity. Growing evidence of the heterogeneity and layered organization of the hematopoietic system is leading to a common view that some lymphocyte subsets are functionally different because they follow distinct developmental programs and emerge from distinct waves of lymphoid progenitors. However, understanding the influence of developmental origin and the relative contribution of local microenvironment on the development of these specialized lymphocyte subsets needs further analysis. In this review, we discuss how different pathways followed by developing B cells during ontogeny may contribute to the diverse functions.


A mixed integer programming model to locate traumatic brain injury treatment units in the Department of Veterans Affairs: a case study.
For the Department of Veterans Affairs (VA), traumatic brain injury (TBI) is a significant problem facing active duty military personnel, veterans, their families, and caregivers. The VA has designated TBI treatment as one of its physical medicine and rehabilitation special emphasis programs, thereby providing a comprehensive array of treatment services to those military personnel and veterans with TBI. Timely treatment of TBI is critical in achieving maximal recovery, and being in geographical proximity to a medical center with specialized TBI treatment services is a major determinant of whether such treatment is utilized. We present a mixed integer programming model for locating TBI treatment units in the VA. This model was developed for the VA Rehabilitation Strategic Healthcare Group to assist in locating new TBI treatment units. The optimization model assigns TBI treatment units to existing VA medical centers while minimizing the sum of patient treatment costs, patient lodging and travel costs, and the penalty costs associated with foregone treatment revenue and excess capacity utilization. We demonstrate our model with VA TBI admission data from one of the VA's integrated service networks, and discuss the expected service and cost implications for a range of TBI treatment unit location options.


Late Pleistocene human skull from Hofmeyr, South Africa, and modern human origins.
The lack of Late Pleistocene human fossils from sub-Saharan Africa has limited paleontological testing of competing models of recent human evolution. We have dated a skull from Hofmeyr, South Africa, to 36.2 +/- 3.3 thousand years ago through a combination of optically stimulated luminescence and uranium-series dating methods. The skull is morphologically modern overall but displays some archaic features. Its strongest morphometric affinities are with Upper Paleolithic (UP) Eurasians rather than recent, geographically proximate people. The Hofmeyr cranium is consistent with the hypothesis that UP Eurasians descended from a population that emigrated from sub-Saharan Africa in the Late Pleistocene.


The river Rhine as a source of micropollutants in the canal sediments of the city of Delft (The Netherlands).
This paper presents a statistical analysis of the pollution levels for heavy metals and organic micropollutants at 182 sediment stations in the city canals of Delft. High pollution levels were especially observed in the inner city canal sediments, probably related to the import of polluted river Rhine water. In contrast, the more-or-less isolated outer city sites were generally much less polluted. Regression analysis on the database generally showed highly significant correlations between individual heavy metal contents. The heavy metal contents were usually significantly correlated with polycyclic aromatic hydrocarbons (PAHs) as well. This points to one or more common sources for these micropollutants. Factor analysis and the K-means cluster analysis technique were applied on the above database; it showed a large cluster of stations, nearly all located in the outer city of Delft, characterized by relatively low heavy metal and organic micropollutants' contents. Another cluster of 18 stations, mostly located in the inner city of Delft, possessed intermediate pollution levels, directly related with the supply of river Rhine water. Finally, the stations of a third cluster, situated in the inner city as well, were highly polluted, especially by local pollution sources. The above hypotheses were further supported by a more detailed statistical analysis for a number of inner city stations, together with 10-year river Rhine pollution data.


Lateral resolution and transfer characteristics of vertical scanning white-light interferometers.
White-light interferometers are widely used for high-accuracy topography measurement in industrial and scientific applications. A common way to characterize a white-light interferometer is to assume small surface amplitudes resulting in linear transfer characteristics described by the instrument transfer function (ITF). However, the well-known batwing effect gives rise to systematic errors, causing extra nonlinearity to the ITF. In this paper a model to simulate an interference pattern in the image plane as it is obtained by a vertical scanning white-light interferometer is introduced in order to overcome the limitation of small surface amplitudes. Repeating the simulation procedure for different height positions of the object results in an image stack that can be analyzed by the same algorithms as real measurement data. The simulation results agree with experimental observations: the batwing effect occurs in certain situations and the correct amplitude of a rectangular grating structure can be obtained as long as the structure is optically resolved. Both simulation, as well as experimental results, provide transfer characteristics of broader bandwidth than predicted by theoretical approaches based on linear system behavior.


Mutations in EFHC1 cause juvenile myoclonic epilepsy.
Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.


Putting occupation into practice: occupation as ends, occupation as means.
This article addresses a difficulty that many occupational therapists experience: maintaining occupation as the core of their therapeutic intervention. This difficulty not only results from but also contributes to occupational therapy's struggle with professional identity. Current manifestations of the problem are described as component-driven practice and the narrowing of occupation to basic activities of daily living. The concepts of occupation as ends and occupation as means are proposed as a practical solution to guide treatment planning and merge remediation and adaptation within a single occupational session. Each concept is investigated in terms of its history within the profession and its usefulness for analyzing and solving therapeutic problems. These concepts are discussed as useful guidelines to help occupational therapists not only in their clinical decision making but also in their understanding and expression of the field's unique expertise. A case example, applying occupation as ends and occupation as means to evaluation and treatment, is presented.