SIMILARITIES AND DIFFERENCES IN WOMEN'S SEXUAL ASSAULT EXPERIENCES BASED ON TACTICS USED BY THE PERPETRATOR.
Only a few studies have examined the characteristics of sexual assault based on the tactics used by the perpetrator. In this study we compared the experiences of women who were forced to engage in vaginal, anal, or oral intercourse due to verbal coercion, physical force, or intoxication. Random-digit dialing was used to obtain a sample of 272 single African American and Caucasian women between the ages of 18 and 49 from the Detroit metropolitan area. Participants completed a computer-assisted self-interview that asked detailed questions about a past sexual assault and their reactions to it. Among the 139 women who were forced to engage in vaginal, anal, or oral intercourse, sexual assaults that involved physical force produced the most severe negative outcomes. Situations that involved the woman being too intoxicated to resist differed from others primarily in terms of how much alcohol the man and woman consumed. Although all types of sexual assault were perceived as being at least moderately serious, verbally coerced assaults were on average perceived as being least serious. These findings suggest that the perpetrators' tactics affect women's responses to sexual assault.


Weighted averaging in spectroscopic studies improves statistical power.
In vivo MRS is often characterized by a spectral signal-to-noise ratio (SNR) that varies highly between experiments. A common design for spectroscopic studies is to compare the ratio of two spectral peak amplitudes between groups, e.g. individual PCr/γ-ATP ratios in 31 P-MRS. The uncertainty on this ratio is often neglected. We wished to explore this assumption. The canonical theory for the propagation of uncertainty on the ratio of two spectral peaks and its incorporation in the Frequentist hypothesis testing framework by weighted averaging is presented. Two retrospective re-analyses of studies comparing spectral peak ratios and one prospective simulation were performed using both the weighted and unweighted methods. It was found that propagating uncertainty correctly improved statistical power in all cases considered, which could be used to reduce the number of subjects required to perform an MR study. The variability of in vivo spectroscopy data is often accounted for by requiring it to meet an SNR threshold. A theoretically sound propagation of the variable uncertainty caused by quantifying spectra of differing SNR is therefore likely to improve the power of in vivo spectroscopy studies. Magn Reson Med 78:2082-2094, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.


Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem.
Because of their agricultural value, there is a great body of research dedicated to understanding the microorganisms responsible for rumen carbon degradation. However, we lack a holistic view of the microbial food web responsible for carbon processing in this ecosystem. Here, we sampled rumen-fistulated moose, allowing access to rumen microbial communities actively degrading woody plant biomass in real time. We resolved 1,193 viral contigs and 77 unique, near-complete microbial metagenome-assembled genomes, many of which lacked previous metabolic insights. Plant-derived metabolites were measured with NMR and carbohydrate microarrays to quantify the carbon nutrient landscape. Network analyses directly linked measured metabolites to expressed proteins from these unique metagenome-assembled genomes, revealing a genome-resolved three-tiered carbohydrate-fuelled trophic system. This provided a glimpse into microbial specialization into functional guilds defined by specific metabolites. To validate our proteomic inferences, the catalytic activity of a polysaccharide utilization locus from a highly connected metabolic hub genome was confirmed using heterologous gene expression. Viral detected proteins and linkages to microbial hosts demonstrated that phage are active controllers of rumen ecosystem function. Our findings elucidate the microbial and viral members, as well as their metabolic interdependencies, that support in situ carbon degradation in the rumen ecosystem.


Gene loops juxtapose promoters and terminators in yeast.
Mechanistic analysis of transcriptional initiation and termination by RNA polymerase II (PolII) indicates that some factors are common to both processes. Here we show that two long genes of Saccharomyces cerevisiae, FMP27 and SEN1, exist in a looped conformation, effectively bringing together their promoter and terminator regions. We also show that PolII is located at both ends of FMP27 when this gene is transcribed from a GAL1 promoter under induced and noninduced conditions. Under these conditions, the C-terminal domain of the large subunit of PolII is phosphorylated at Ser5. Notably, inactivation of Kin28p causes a loss of both Ser5 phosphorylation and the loop conformation. These data suggest that gene loops are involved in the early stages of transcriptional activation. They also predict a previously unknown structural dimension to gene regulation, in which both ends of the transcription unit are defined before and during the transcription cycle.


Diverging trends in incidence and mortality, and improved survival of non-Hodgkin's lymphoma, in the Netherlands, 1989-2007.
We studied progress in the fight against non-Hodgkin's lymphoma (NHL) in the Netherlands by describing the changes in incidence, treatment, relative survival, and mortality during 1989-2007. We included all adult patients with NHL [i.e. all mature B-, T-, and natural killer (NK) cell neoplasms, with the exception of plasma cell neoplasms], newly diagnosed in the period 1989-2007 and recorded in the Netherlands Cancer Registry (n=55 069). Regular mortality data were derived from Statistics Netherlands. Follow-up was completed up to 1 January 2009. Annual percentages of change in incidence, mortality, and relative survival were calculated. The incidence of indolent B-cell and T- and NK-cell neoplasms rose significantly (estimated annual percentage change=1.2% and 1.3%, respectively); incidence of aggressive B-cell neoplasms remained stable. Mortality due to NHL remained stable between 1989 and 2003, and has decreased since 2003. Five-year relative survival rates rose from 67% to 75%, and from 43% to 52%, respectively, for indolent and aggressive mature B-cell neoplasms, but 5-year survival remained stable at 48% for T- and NK-cell neoplasms. In the Netherlands, incidence of indolent mature B-cell and mature T- and NK-cell neoplasms has increased since 1989 but remained stable for aggressive neoplasms. Survival increased for all mature B-cell neoplasms, preceding a declining mortality and increased prevalence of NHL (17 597 on 1 January 2008).


Anti-bacterial and anti-inflammatory effects of ethanol extract from Houttuynia cordata poultice.
Houttuynia cordata (HC) has been commonly used as many traditional remedies in local areas of Japan. Although many pharmacological activities of HC have been reported, the mechanism underlying the effect of HC remains unknown. We conducted the interview survey in Japan to verify how HC was actually used. The interview survey revealed that HC poultice (HCP) prepared from smothering fresh leaves of HC was most frequently used for the treatment of purulent skin diseases including furuncle and carbuncle with high effectiveness. Ethanol extract of HCP (eHCP) showed anti-bacterial effects against methicillin-resistant Staphylococcus aureus (MRSA), and showed an anti-biofilm activity against MRSA. eHCP showed dose-dependent inhibition of S. aureus lipoteichoic acid (LTA)-induced interleukin-8 and CCL20 production in human keratinocyte without any cytotoxicity. These results suggest that HCP is effective for skin abscess and its underlying mechanism might be the complicated multiple activities for both bacteria and host cells.


Ozonation of iodide-containing waters: selective oxidation of iodide to iodate with simultaneous minimization of bromate and I-THMs.
The presence of iodinated disinfection by-products (I-DBPs) in drinking water poses a potential health concern since it has been shown that I-DBPs are generally more genotoxic and cytotoxic than their chlorinated and brominated analogs. I-DBPs are formed during oxidation/disinfection of iodide-containing waters by reaction of the transient hypoiodous acid (HOI) with natural organic matter (NOM). In this study, we demonstrate that ozone pre-treatment selectively oxidizes iodide to iodate and avoids the formation of I-DBPs. Iodate is non-toxic and is therefore a desired sink of iodine in drinking water. Complete conversion of iodide to iodate while minimizing the bromate formation to below the guideline value of 10 μg L⁻¹ was achieved for a wide range of ozone doses in five raw waters with DOC and bromide concentrations of 1.1-20 mg L⁻¹ and 170-940 μg L⁻¹, respectively. Lowering the pH effectively further reduced bromate formation but had no impact on the extent of iodate and bromoform formation (the main trihalomethane (THM) formed during ozonation). Experiments carried out with pre-chlorinated/post-clarified samples already containing I-DBPs, showed that ozonation effectively oxidized I-THMs. Therefore, in iodide-containing waters, in which I-DBPs can be produced upon chlorination or especially chloramination, a pre-ozonation step to oxidize iodide to iodate is an efficient process to mitigate I-DBP formation.


Genetic evidence for the convergent evolution of light skin in Europeans and East Asians.
Human skin pigmentation shows a strong positive correlation with ultraviolet radiation intensity, suggesting that variation in skin color is, at least partially, due to adaptation via natural selection. We investigated the evolution of pigmentation variation by testing for the presence of positive directional selection in 6 pigmentation genes using an empirical F(ST) approach, through an examination of global diversity patterns of these genes in the Centre d'Etude du Polymorphisme Humain (CEPH)-Diversity Panel, and by exploring signatures of selection in data from the International HapMap project. Additionally, we demonstrated a role for MATP in determining normal skin pigmentation variation using admixture mapping methods. Taken together (with the results of previous admixture mapping studies), these results point to the importance of several genes in shaping the pigmentation phenotype and a complex evolutionary history involving strong selection. Polymorphisms in 2 genes, ASIP and OCA2, may play a shared role in shaping light and dark pigmentation across the globe, whereas SLC24A5, MATP, and TYR have a predominant role in the evolution of light skin in Europeans but not in East Asians. These findings support a case for the recent convergent evolution of a lighter pigmentation phenotype in Europeans and East Asians.


ARNT controls the expression of epidermal differentiation genes through HDAC- and EGFR-dependent pathways.
Previously we showed that spatial and developmental modulation of ARNT (HIF1β) expression in mouse epidermis is essential for maintenance of keratinocyte differentiation, proper formation of the barrier and normal desquamation. Here, using lentiviral suppression or induction of ARNT in TERT-immortalized (N-TERT) and HaCaT cells we assessed the nature and mechanisms of ARNT involvement in control of differentiation in human epidermal keratinocytes. ARNT depletion did not affect the levels of basal keratins K5 and K14, but significantly induced expression of several key differentiation markers (an effect abolished by EGF supplementation). Furthermore, ARNT deficiency resulted in the downregulation of amphiregulin (AREG) - the most highly expressed EGFR ligand in human keratinocytes - whereas upregulation of ARNT showed the opposite. In ARNT-deficient monolayer cultures and 3D epidermal equivalents, the downregulation of AREG was concurrent with a decline of EGFR and ERK1/2 phosphorylation. TSA, a potent suppressor of HDAC activity, abolished the effects of ARNT deficiency, implying a role for HDACs in ARNT-dependent modulation of the AREG-EGFR pathway and downstream epidermal genes. Total HDAC activity was significantly increased in ARNT-depleted cells and decreased with ARNT overexpression. ARNT-dependent shifts in HDAC activity were specifically attributed to significant changes in the levels of HDAC1, HDAC2 and HDAC3 proteins (but not mRNA) in both monolayer and 3D cultures. Collectively, our results suggest that ARNT controls AREG expression and the downstream EGFR-ERK pathway in keratinocytes, at least in part, by modulating HDAC activity. This novel regulatory pathway targeting advanced stages of epidermal differentiation might have important implications for skin pathology such as psoriasis, atopic dermatitis and cancer.


A shared statement of ethical principles for those who shape and give health care: a working draft from the Tavistock group.
Health care delivery in many countries has expanded over the past 150 years from a largely social service delivered by individual practitioners to an intricate network of services provided by teams of professionals. The problems of increasing resource consumption, financial constraints, complexity, and poor system design that have emerged as consequences of these changes have exacerbated many of the ethical tensions inherent in health care and have created new ones. Many groups of professionals that give and affect health care have established separate codes of ethics for their own disciplines, but no shared code exists that might bring all stakeholders in health care into a more consistent moral framework. A multidisciplinary group therefore recently met at Tavistock Square in London in an effort to prepare such a shared code. The result was not a code but a more basic and generic statement of ethical principles. The intent and hope is that it will offer clear guidance for tough calls in real world settings. It is presented here not as a finished work, but as a draft to elicit comment, critique, suggestions for revision, and, especially, ideas for implementation.


Coronary flow in a perfused rainbow trout heart.
A preparation was developed to perfuse the coronary circulation in working hearts from rainbow trout (Salmo gairdneri Richardson). The preparation was used to examine pressure-flow relationships for the coronary circulation as the heart generated physiological and subphysiological work loads. Coronary vascular resistance increased exponentially as coronary flow rate decreased. Coronary resistance was also influenced by cardiac metabolism and acclimation temperature. When heart rate was increased, extravascular compression increased in coronary resistance. Direct vasoconstriction of the coronary vessels, produced by injections of adrenaline into the coronary circulation, was temperature-dependent.


Decisions for lung cancer chemotherapy: the influence of physician and patient factors.
The purpose of this study is to review the literature examining how the beliefs and behaviours of physicians and patients influence clinical communication, doctor-patient interaction and treatment decisions for lung cancer treatment. Literature was obtained via electronic database searches and hand searching of journals from 1990 to 2011. Wide variability in perceptions of the value of chemotherapy in lung cancer is present among both physicians and patients. There is a mismatch in the degree patients and physicians weigh survival, such that patients value survival benefits highly whilst physicians strongly emphasize toxicity and associated symptoms. This lack of congruence between patients and clinicians is influenced by a range of factors and has implications for treatment decisions, long-term survival and quality of life in people affected by lung cancer. The divergence of treatment priorities indicates a need for improved communication strategies addressing the needs and concerns of both patients and clinicians. Patients should understand the benefits and risks of treatment options, while clinicians can gain a greater awareness of factors influencing patients' decisions on treatments. Reflecting these perspectives and patient preferences for lung cancer treatment in clinical guidelines may improve clinician awareness.


Perceived weight status and weight change among a U.S. adult sample.
Examine bidirectional associations between weight perception and weight change over time among adults. Data are from adult employees (N = 623) across 12 U.S. public high schools participating in a cluster-randomized multilevel weight gain prevention intervention. Data were collected at baseline, 12 months, and 24 months. Perceived weight status (very/somewhat underweight, just right, somewhat overweight, very overweight) were obtained via self-administered surveys. Weight (kg) was measured by trained staff. Change in weight was calculated as the difference between baseline weight and weight at each follow-up time point. Structural equation models were used to assess bidirectional associations of perceived weight status and change in weight over time. Models were adjusted for study condition, gender, age, race/ethnicity, education level, and previous time point. The sample was 65% female with a mean age of 44.6 (SD = 11.3). Nearly two thirds of the sample consisted of people with overweight (38.8%) or obesity (27.3%). Structural equation models indicated that baseline weight predicted subsequent perceived weight status (β = 0.26; P < 0.001), whereas baseline perceived weight status did not predict subsequent change in weight, adjusting for previous time point and covariates. Results do not support bidirectional causality between weight perception and weight change in an adult sample.


Noradrenaline secretion by the human kidney.
1. In 20 subjects with uncomplicated essential hypertension, 10 of whom were on propranolol treatment, several blood samples were drawn simultaneously from the renal artery and vein after angiographic studies. In these samples we determined concentrations of noradrenaline, active renin, aldosterone and cortisol. 2. Renal blood flow was measured in all patients by Hippuran-clearance and xenon-washout. 3. Despite marked variations in the arteriovenous difference of noradrenaline, it was apparent in both groups that the kidney is able to release noradrenaline. 4. In the propranolol-treated group noradrenaline secretion with untreated hypertensive patients.


Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.
Safe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia. This phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801. Between Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p<0·0001). Early mortality was similar between treatment groups (30-day: 28 [8%] of 355 patients in the vosaroxin plus cytarabine group vs 23 [7%] of 350 in the placebo plus cytarabine group; 60-day: 70 [20%] vs 68 [19%]). Treatment-related deaths occurred at any time in 20 (6%) of 355 patients given vosaroxin plus cytarabine and in eight (2%) of 350 patients given placebo plus cytarabine. Treatment-related serious adverse events occurred in 116 (33%) and 58 (17%) patients in each group, respectively. Grade 3 or worse adverse events that were more frequent in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group included febrile neutropenia (167 [47%] vs 117 [33%]), neutropenia (66 [19%] vs 49 [14%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), bacteraemia (43 [12%] vs 16 [5%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Although there was no significant difference in the primary endpoint between groups, the prespecified secondary analysis stratified by randomisation factors suggests that the addition of vosaroxin to cytarabine might be of clinical benefit to some patients with relapsed or refractory acute myeloid leukaemia. Sunesis Pharmaceuticals.


Occupational Therapy Practice Guidelines for People With Parkinson's Disease.
Occupational therapy practitioners address the occupational performance and participation needs of people with Parkinson's disease (PD) and their care partners. This Practice Guideline is informed by systematic reviews on the use of occupational therapy interventions to promote participation in occupations for people with PD and to facilitate their caregivers' participation in the caregiver role. This guideline is meant to support practitioners' clinical decision making when working with people with PD and their care partners. We examined and synthesized the results of four systematic reviews and integrated those results into clinical recommendations for practice. Thirty-three articles from the systematic reviews served as the basis for the clinical recommendations in this Practice Guideline. Clinical recommendations are provided for interventions that have strong or moderate supporting evidence. Multidisciplinary, tailored, goal-oriented intervention is recommended for people with PD. Various forms of exercise can be used to improve activities of daily living and instrumental activities of daily living performance and social participation, and interventions should incorporate health behavior change techniques to support adequate physical activity levels in daily life. Mindfulness meditation and exercise can be used to support sleep, and task-oriented training can be used to improve performance of specific tasks. Occupational therapy practitioners should incorporate self-management, coaching, compensatory, cognitive-behavioral, and other approaches into multicomponent treatment plans depending on the client's needs and goals. Additional potentially appropriate intervention approaches or areas to address are discussed on the basis of existing or emerging evidence and expert opinion. What This Article Adds: This Practice Guideline provides a summary and applications of the current evidence supporting occupational therapy intervention for people with PD. It includes case examples and suggested decision-making algorithms to support practitioners in addressing client goals.


Measurement of muscle contraction with ultrasound imaging.
To investigate the ability of ultrasonography to estimate muscle activity, we measured architectural parameters (pennation angles, fascicle lengths, and muscle thickness) of several human muscles (tibialis anterior, biceps brachii, brachialis, transversus abdominis, obliquus internus abdominis, and obliquus externus abdominis) during isometric contractions of from 0 to 100% maximal voluntary contraction (MVC). Concurrently, electromyographic (EMG) activity was measured with surface (tibialis anterior only) or fine-wire electrodes. Most architectural parameters changed markedly with contractions up to 30% MVC but changed little at higher levels of contraction. Thus, ultrasound imaging can be used to detect low levels of muscle activity but cannot discriminate between moderate and strong contractions. Ultrasound measures could reliably detect changes in EMG of as little as 4% MVC (biceps muscle thickness), 5% MVC (brachialis muscle thickness), or 9% MVC (tibialis anterior pennation angle). They were generally less sensitive to changes in abdominal muscle activity, but it was possible to reliably detect contractions of 12% MVC in transversus abdominis (muscle length) and 22% MVC in obliquus internus (muscle thickness). Obliquus externus abdominis thickness did not change consistently with muscle contraction, so ultrasound measures of thickness cannot be used to detect activity of this muscle. Ultrasound imaging can thus provide a noninvasive method of detecting isometric muscle contractions of certain individual muscles.


Isoproterenol downregulation of statin-related gene expression in the rat parotid gland.
Statin, a 57 kilodalton (kDa) nuclear protein, is characteristically found in nonproliferating cells in culture as well as nondividing cells of a wide range of highly differentiated tissues. Moreover, cells in culture that are statin positive lose this statin expression when re-entering the cell-cycle traverse. In this work, statin expression was investigated in the parotid gland of untreated rats and those treated with isoproterenol (IPR), a proliferation-inducing catecholamine. Indirect immunofluorescence microscopy revealed specific nuclear staining with anti-statin monoclonal antibody (S-44) in the acinar and ducts cells of the untreated rats but significantly reduced in those induced with isoproterenol. To characterize the protein recognized by S-44, protein extracts from both tissues were immunoblotted and incubated with S-44. The antibody reacted specifically with a 48 kDa protein in the extract of the parotid glands from untreated rats while no reaction was detected in that of the proliferation-induced ones. These observations along with the result that a statin-like (S1) transcript is downregulated by isoproterenol in the parotid glands further support the notion that the disappearance of statin-related expression is associated with the IPR-induced proliferation in the rat parotid glands. The discrepancy between the apparent molecular mass of the protein identified by S-44 in nonproliferating parotid cells and that of statin originally found in fibroblasts, suggests that either a modified form of statin may be present in the parotid gland, or this 48 kDa protein may be a member of the nonproliferative statin-like family.


The response of carbohydrate metabolism in potato tubers to low temperature.
This work investigates the possible causes of cold-induced sweetening in potato by examining the impact of low temperature on carbohydrate metabolism in mature tubers. Metabolism in tuber discs was monitored by determining the redistribution of radiolabel following incubation in [U-(14)C]glucose. Estimates of flux based on the specific activity of hexose phosphates established that while incubation at 4 degrees C resulted in an immediate restriction in pathways of carbohydrate oxidation relative to activity at 25 degrees C, there was no corresponding increase in flux to soluble sugars. In contrast, prior storage at low temperature stimulated flux to sugars at both 4 and 25 degrees C. Comparison of (14)CO(2) release from specifically labeled glucose and gluconate fed to tuber discs at 4 and 25 degrees C indicated that flux through glycolysis was preferentially restricted relative to the oxidative pentose phosphate pathway at low temperature, irrespective of prior storage temperature. However, the degree of randomization of label between positions C1 and C6 in the fructosyl moiety of sucrose following metabolism of [1-(13)C]glucose established that there was no preferential inhibition of the recycling of triose phosphates to hexose phosphates at low temperature. These results indicate that sugar accumulation in tubers during storage in the cold is not a direct consequence of a constraint in carbohydrate oxidation, despite preferential restriction of glycolysis at low temperature. It is concluded that the cold lability of enzymes catalyzing the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate is not a major factor in cold-induced sweetening in plants and that this widely held hypothesis should be abandoned.


Preschool children physical activity measurement: importance of epoch length choice.
The purpose of this study was twofold: first to document the gender differences in Moderate to Vigorous Physical Activity (MVPA) according to two epoch systems (5 vs. 60 s) in preschoolers, and, second to document the differences in physical activity (PA) patterns according to two different epoch choices. The sample comprised 59 preschoolers (31 girls) aged 2-5 years old. PA was assessed by accelerometer during school hours. The time spent in MVPA was significantly higher (p < .001) when a 5-s epoch was considered compared to the 60-s epoch, regardless gender. Further, it was found a difference of ?17 min difference between the 2 epoch systems for MVPA. Different epoch times might affect the time spent in MVPA among preschool children.


The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons.
Impaired axonal transport may play a key role in Parkinson's disease. To test this notion, a microchamber system was adapted to segregate axons from cell bodies using green fluorescent protein-labeled mouse dopamine (DA) neurons. Transport was examined in axons challenged with the DA neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+). MPP+ rapidly reduced overall mitochondrial motility in DA axons; among motile mitochondria, anterograde transport was slower yet retrograde transport was increased. Transport effects were specific for DA mitochondria, which were smaller and transported more slowly than their non-DA counterparts. MPP+ did not affect synaptophysin-tagged vesicles or any other measureable moving particle. Toxin effects on DA mitochondria were not dependent upon ATP, calcium, free radical species, JNK, or caspase3/PKC pathways but were completely blocked by the thiol-anti-oxidant N-acetyl-cysteine or membrane-permeable glutathione. Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve "normal" circuitry and function as long as possible.


Amniotic fluid index versus single deepest vertical pocket as a screening test for preventing adverse pregnancy outcome.
Amniotic fluid volume is an important parameter in the assessment of fetal well-being. Oligohydramnios occurs in many high-risk conditions and is associated with poor perinatal outcomes. Many caregivers practice planned delivery by induction of labor or caesarean section after diagnosis of decreased amniotic fluid volume at term. There is no clear consensus on the best method to assess amniotic fluid adequacy. To compare the use of the amniotic fluid index with the single deepest vertical pocket measurement as a screening tool for decreased amniotic fluid volume in preventing adverse pregnancy outcome. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007) and the metaRegister of Controlled Trials (May 2007). We handsearched the citation lists of relevant publications, review articles, and included studies. Randomised controlled trials involving women with a singleton pregnancy, whether at low or high risk, undergoing ultrasound measurement of amniotic fluid volume as part of antepartum assessment of fetal well-being that compared the amniotic fluid index and the single deepest vertical pocket measurement. Both authors independently assessed eligibility and quality, and extracted the data. Four trials (3125 women) met the inclusion criteria. There is no evidence that one method is superior to the other in the prevention of poor peripartum outcomes, including: admission to a neonatal intensive care unit; an umbilical artery pH of less than 7.1; the presence of meconium; an Apgar score of less than 7 at five minutes; or caesarean delivery. When the amniotic fluid index was used, significantly more cases of oligohydramnios were diagnosed (risk ratio (RR, random) 2.33, 95% CI 1.67 to 3.24), and more women had inductions of labor (RR (fixed) 2.10, 95% CI 1.60 to 2.76) and caesarean delivery for fetal distress (RR (fixed) 1.45, 95% CI 1.07 to 1.97). The single deepest vertical pocket measurement in the assessment of amniotic fluid volume during fetal surveillance seems a better choice since the use of the amniotic fluid index increases the rate of diagnosis of oligohydramnios and the rate of induction of labor without improvement in peripartum outcomes. A systematic review of the diagnostic accuracy of both methods in detecting decreased amniotic fluid volume is required.


Performance evaluation of Active Melioidosis Detect-Lateral Flow Assay (AMD-LFA) for diagnosis of melioidosis in endemic settings with limited resources.
Melioidosis is a fatal infection caused by the soil saprophyte Burkholderia pseudomallei. Early diagnosis and befitting medical management can significantly influence the clinical outcomes among patients with melioidosis. Witnessing an annual increment in the number of melioidosis cases, over the past few years, mainly from the developing tropical nations, the present study was undertaken to evaluate the diagnostic utility of Active Melioidosis DetectTMLateralFlow Assay (AMD-LFA), in comparison with enrichment culture and PCR. A total of 206clinical specimens obtained from 175 patients with clinical suspicion of melioidosis were considered for the evaluation. Positivity for B.pseudomallei using enrichment culture, PCR and AMD-LFA were observed among 63 (30.5%), 55 (26.6%) and 63 (30.5%) specimens respectively. The AMD-LFA failed to detect melioidosis from 9 culture-confirmed cases (6 whole blood specimens, 2 pus samples, and one synovial fluid). Further the test gave faint bands from 9 urine samples which were negative by culture and PCR. AMD-LFA demonstrated a sensitivity, specificity, of 85.71%(CI:74.61% to 93.25%) and 93.62% (CI:88.23% to 97.04%), with positive predictive value of 85.71% (CI: 75.98% to 91.92%) and negative predictive value of 93.62% (CI:88.89% to 96.42%). The test needs further evaluation in view of the faint bands from negative urine samples, for incorporating the test as a point of care assay.In view of its rapidity and ease of testing AMD-LFA might be useful in early diagnosis of melioidosis at resource constraint settings.


PRKCH polymorphism is associated with rheumatoid arthritis in a Chinese population.
Genetic factors have been widely considered to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). The purpose of this study was to determine whether the four newly discovered polymorphisms in a genome-wide association study (GWAS) meta-analysis confer susceptibility to RA in a Chinese Han population. We conducted a case-control study involving 359 RA cases and 873 age-and gender-matched controls and performed genotyping of four single nucleotide polymorphisms (SNPs), rs227163, rs726288, rs3783782 and rs2469434, using the dye terminator-based SNaPshot method. Consequently, we detected significant differences of genotype distribution of rs3783782 in PRKCH between RA and controls. The minor allele frequencies (MAFs) of rs3783782 were significantly higher in RA patients compared to control subjects. Moreover, the rs227163 in TNFRSF9 had higher MAFs in male RA compared with male controls. In addition, the polymorphism of rs3783782 in PRKCH was significantly associated with RA susceptibility (OR = 1.67, 95% CI = 1.32-2.11, p = 1.32 × 10-5). After stratification by gender, the minor (A) allele was strongly associated with increased risk for RA in males (OR = 1.87, 95% CI = 1.34-2.60; p = 1.62 × 10-4) and in females (OR = 1.51, 95% CI = 1.08-2.10; p = 0.014). For rs227163, the minor (C) allele was found to be associated with RA risk only in males (OR = 1.34, 95% CI = 1.02-1.75; p = 0.036). These findings for the first time confirmed that rs3783782 in PRKCH was associated with RA susceptibility in a Chinese population, and rs227163 in TNFRSF9 was associated with RA risk in Chinese males; these SNPs may serve as genetic markers for RA.


Can coffee consumption lower the risk of Alzheimer's disease and Parkinson's disease? A literature review.
In light of the fact that the number of elderly citizens in society is steadily increasing, the search for dietary factors which might prolong mental agility is growing in significance. Coffee, together with its main ingredient, caffeine, has been the focus of much attention from various researchers, as data on its beneficial effects on human health continue to accumulate. Most reports indicate that moderate coffee consumption may in fact lower the risk for common neurodegenerative conditions, i.e. Alzheimer's and Parkinson's diseases. Regardless, due to their complex pathogenesis as well as methodology of scientific research, the exact impact of coffee consumption remains to be fully elucidated. At present, it seems safe to inform the general public that coffee drinkers need not fear for their health. Possibly, in the future experts will recommend drinking coffee not only to satisfy individual taste preferences but also to decrease age-related mental deterioration.


Reduced pancreatic polypeptide response to hypoglycemia and amylin response to arginine in subjects with a mutation in the HNF-4alpha/MODY1 gene.
Subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha gene (RW pedigree/maturity-onset diabetes of the young [MODY]-1) have diminished insulin and glucagon secretory responses to arginine. To determine if pancreatic polypeptide (PP) secretion is likewise involved, we studied PP responses to insulin-induced hypoglycemia in 17 RW pedigree members: 6 nondiabetic mutation-negative [ND(-)], 4 nondiabetic mutation-positive [ND(+)], and 7 diabetic mutation-positive [D(+)]. Subjects received 0.08 U/kg body wt human regular insulin as an intravenous bolus to produce moderate self-limited hypoglycemia. PP areas under the curve (PP-AUCs) were compared among groups. With hypoglycemia, the PP-AUC was lower in the D(+) group (14,907 +/- 6,444 pg/ml, P = 0.03) and the ND(+) group (14,622 +/- 6,015 pg/ml, P = 0.04) compared with the ND(-) group (21,120 +/- 4,158 pg/ml). In addition, to determine if the beta-cell secretory defect in response to arginine involves amylin in addition to insulin secretion, we analyzed samples from 17 previously studied RW pedigree subjects. We compared the AUCs during arginine infusions for the 3 groups both at euglycemia and hyperglycemia as well as their C-peptide-to-amylin ratios. The D(+) and ND(+) groups had decreased amylin AUCs during both arginine infusions compared with the ND(-) group, but had similar C-peptide-to-amylin ratios. These results suggest that the HNF-4alpha mutation in the RW/MODY1 pedigree confers a generalized defect in islet cell function involving PP cells in addition to beta- and alpha-cells, and beta-cell impairment involving proportional deficits in insulin and amylin secretion.


Seasonal patterns in fecundability in North America and Denmark: a preconception cohort study.
To what extent does fecundability vary across seasons? After accounting for seasonal patterns in pregnancy planning, we observed higher fecundability in the fall and lower fecundability in the spring, particularly at lower latitudes. In human populations, there are strong seasonal patterns of births that vary across geographic regions and time periods. However, previous studies of seasonality and fecundity are limited because they examine season of birth rather than season of conception and therefore neglect to account for seasonal variation in initiating attempts to conceive or pregnancy loss or differences in gestational length. We conducted a preconception cohort study of 14 331 women residing in North America (June 2013-May 2018: n = 5827) and Denmark (June 2007-May 2018: n = 8504). Participants were attempting to conceive without fertility treatment and had been attempting pregnancy for ≤6 menstrual cycles at enrolment. We collected information on season of each pregnancy attempt using last menstrual period dates over the study period. Pregnancy was reported on female bi-monthly follow-up questionnaires. We fit log-binomial models with trigonometric regression to examine periodic variation in fecundability. We accounted for seasonal variation in initiation of pregnancy attempts by including indicator variables for menstrual cycle of attempt in the regression models. Initiation of pregnancy attempts peaked in September, with stronger seasonality in North America than in Denmark (48 vs. 16% higher probability initiating attempts in September compared with March). After accounting for seasonal variation in initiation of pregnancy attempts, we observed modest seasonal variation in fecundability, with a peak in the late fall and early winter in both cohorts, but stronger peak/low ratios in North America (1.16; 95% confidence interval [CI]: 1.05, 1.28) than in Denmark (1.08; 95% CI: 1.00, 1.16). When we stratified the North American data by latitude, we observed the strongest seasonal variation in the southern USA (peak/low ratio of 1.45 [95% CI: 1.14, 1.84]), with peak fecundability in late November. We estimated menstrual cycle dates between follow-up questionnaires, which may have introduced exposure misclassification, particularly when women skipped follow-up questionnaires. We were unable to measure seasonally varying factors that may have influenced fecundability, including ambient temperature, vitamin D levels or infectious disease. An understanding of how fecundability varies across seasons could help identify factors that can impair reproductive function. Neglecting to account for seasonal variation in initiation of pregnancy attempts could bias estimates of seasonal patterns in fecundability. This is the first preconception cohort study to examine seasonal variation in fecundability after accounting for seasonality in initiation of pregnancy attempts. Fecundability was highest in the fall and lowest in the spring, with stronger effects in southern latitudes of North America, suggesting that seasonal exposures may affect fecundity. This research was funded by the Eunice K. Shriver National Institute of Child Health and Human Development (R21-050264, R01-HD060680, R21-HD072326 and R01-HD086742) and the Danish Medical Research Council (271-07-0338). The authors declare no conflicts of interest.


Genomic integrity in the male germ line: evidence in support of the disposable soma hypothesis.
The Big Blue λSelect-cII selection system has been employed along with whole-exome sequencing to examine the susceptibility of the male germ line to mutation in two challenging situations (i) exposure to a chemotherapeutic regime including bleomycin, etoposide and cis-platinum (BEP) and (ii) the ageing process. A 3-week exposure to BEP induced complete azoospermia associated with a loss of developing germ cells and extensive vacuolization of Sertoli cell cytoplasm. Following cessation of treatment, spermatozoa first appeared in the caput epididymis after 6 weeks and by 12 weeks motile spermatozoa could be recovered from the cauda, although the count (P < 0.001) and motility (P < 0.01) of these cells were significantly reduced and superoxide generation was significantly elevated (P < 0.001). Despite this increase in free radical generation, no evidence of chromatin instability was detected in these spermatozoa. Furthermore, embryos obtained from females mated at this 12-week time point showed no evidence of an increased mutational load. Similarly, progressive ageing of Big Blue mice had no impact on the quality of the spermatozoa, fertility or mutation frequency in the offspring despite a significant increase in the mutational load carried by somatic tissues such as the liver (P < 0.05). We conclude that the male germ line is highly resistant to mutation in keeping with the disposable soma hypothesis, which posits that genetic integrity in the germ cells will be maintained at the expense of the soma, in light of the former's sentinel position in safeguarding the stability of the genome.


Associations between Psychological Problems and Quality of Life in Pediatric Short Stature from Patients' and Parents' Perspectives.
Short stature has been associated with psychosocial impairments, but whether treatments and achieved height impact on health-related quality of life (HrQoL) and psychological functioning of children/adolescents is still controversial. This study aimed to examine the effects of height deviation and treatment status on psychosocial adaptation outcomes and to identify clinical and psychosocial determinants of internalizing/externalizing problems in a large cohort of short statured children/adolescents from seven European countries. Participants were 345 children aged 8-18 years with a clinical diagnosis of short stature and 421 parents of 4-18 year-old patients. Children and parents reported on psychological problems (Strengths and Difficulties Questionnaire), generic (KIDSCREEN) and condition-specific HrQoL (QoLISSY). According to analyses of covariance, children/adolescents with current short stature presented more parent-reported internalizing problems and lower self- and parent-reported condition-specific HrQoL, compared to patients with an achieved height above -2SD. Treated children self-reported better HrQoL than the untreated group. Hierarchical regression analysis showed that, rather than height-related clinical variables, children's sex, younger age and poorer HrQoL were the best predictors of psychological problems, explaining 39% of the variance in patient- and 42% in parent-reported internalizing problems, and 22% of the variance in patient- and 24% in parent-reported externalizing problems. Treatment status also moderated the negative links between patient-reported HrQoL and internalizing problems, explaining 2% of additional variance. These results suggest that children with current short stature are at greater risk for internalizing problems. Routine assessment of HrQoL in pediatric healthcare may help identify children for referral to specialized psychological assessment and intervention.


What influences antibiotic sales in rural Bangladesh? A drug dispensers' perspective.
Antibiotic resistance poses a great threat to global health, especially in low- and middle-income countries with a high infectious disease burden and limited resources. In spite of regulations, antibiotics are sold in many settings as non-prescription medicines, resulting in inappropriate use and resistance. This study aimed to investigate the current status of access and use of antibiotics in rural Bangladesh, by exploring the perspectives and sales practices of antibiotic drug dispensers. We used a mixed methods approach (qualitative and quantitative). We mapped and characterized antibiotic purchasing and dispensing sites in the Matlab Health and Demographic Surveillance System catchment area. Furthermore, we investigated the volume of provision of systemic antibiotics in 10 drug outlets. We held 16 in-depth interviews with randomly selected antibiotics dispensers. Interviews explored factors associated with antibiotic selling. Responses were transcribed, coded for themes, and summarized. We used ATLAS.ti 5.2 for conducting a thematic analysis. A total of 301 antibiotic dispensers were identified, of whom 92% (n = 278) were private and 8% (n = 23) public. 52% (n = 155) operated informally (i.e. without legal authorization). In order to promote and survive in their business, dispensers sell antibiotics for a range of conditions without a qualified physician's prescription. Factors that facilitate these inappropriate sales include lack of access to healthcare in the rural community, inadequate doctor: population ratio, limited dispenser knowledge, poor pharmacovigilance concerning safety of self medication, lack of enforcement of policies, financial benefits for both customers and dispensers, and high dependency on pharmaceutical companies' information. Dispensers in rural Bangladesh sell antibiotics inappropriately by ignoring existing national regulations. They operate the antibiotic sales without facing any legal barriers and primarily with a view to sustain their business, resulting in inappropriate sales of antibiotics to the rural community. The influence of the drug industry needs to be replaced with evidence-based, not commercially driven information. Awareness programs for antibiotic providers that promote understanding of antibiotics and antibiotic resistance through tailored interventions may be helpful in changing current antibiotic sales practices.


Tele-assistance in chronic respiratory failure patients: a randomised clinical trial.
Chronic respiratory patients requiring oxygen or home mechanical ventilation experience frequent exacerbations and hospitalisations with related costs. Strict monitoring and care have been recommended. The aim of the present study was to primarily evaluate reduction in hospitalisations and, secondly, exacerbations, general practitioner (GP) calls and related cost-effectiveness of tele-assistance (TA) for these patients. A total of 240 patients (101 with chronic obstructive pulmonary disease (COPD)) were randomised to two groups: an intervention group entered a 1-yr TA programme while controls received traditional care. No anthropometric and clinical differences were found between groups both in baseline and in mortality (18% for TA, 23% for controls). Compared with controls, the TA group experienced significantly fewer hospitalisations (-36%), urgent GP calls (-65%) and acute exacerbations (-71%). Only COPD patients, as a separate group, had fewer hospitalisations, emergency room admissions, urgent GP calls or exacerbations. Each patient referred to staff a mean+/-sd 36+/-25 times. After deduction of TA costs, the average overall cost for each patient was 33% less than that for usual care. In chronic respiratory failure patients on oxygen or home mechanical ventilation, a nurse-centred tele-assistance prevents hospitalisations while it is cost-effective. The chronic obstructive pulmonary disease group seems to have a greater advantage from tele-assistance.


Trends in lower respiratory tract infection hospitalizations among American Indian/Alaska Native children and the general US child population.
To describe trends in the rate of hospitalization for lower respiratory tract infection (LRTI) among American Indian/Alaska Native (AI/AN) children and the general US population of children aged <5 years. This was a retrospective analysis of trends and hospitalization rates for LRTI-associated hospitalizations in 1998-2008 among AI/AN children aged <5 years using the Indian Health Service direct/contract inpatient data, and also among the general population of US children aged <5 years using the Nationwide Inpatient Sample. The 2006-2008 LRTI-associated hospitalization rate for AI/AN children aged <5 years (21.8 per 1000/year) was 32% lower than the 1998-1999 rate, and 1.6-fold higher than the general US children rate (13.8 per 1000/year; 95% CI, 12.8-14.8). Higher rates were seen in AI/AN children aged <5 years in the Alaska and the Southwest regions of the United States (41.2 and 28.0 per 1000/year, respectively). In infants, these rates were 136.4 and 82.4 per 1000/year, respectively, exceeding the rate in the general US infant population (37.1 per 1000/year; 95% CI, 34.3-40.0). The greatest disparity in the LRTI-associated hospitalization rate between AI/AN infants and the general US infant population was seen for pneumonia, with a 3-fold higher rate in AI/AN infants (36.2 per 1000/year vs 12.7 per 1000/year; 95% CI, 11.8-13.6). The LRTI-associated hospitalization rate is higher in AI/AN children, particularly infants from Alaska and the American Southwest, compared with the general US child population. Closing this gap will require addressing housing and sanitation inequities and ensuring high immunization rates and access to care.


Anxiety Cells in a Hippocampal-Hypothalamic Circuit.
The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.


SEQADAPT: an adaptable system for the tracking, storage and analysis of high throughput sequencing experiments.
High throughput sequencing has become an increasingly important tool for biological research. However, the existing software systems for managing and processing these data have not provided the flexible infrastructure that research requires. Existing software solutions provide static and well-established algorithms in a restrictive package. However as high throughput sequencing is a rapidly evolving field, such static approaches lack the ability to readily adopt the latest advances and techniques which are often required by researchers. We have used a loosely coupled, service-oriented infrastructure to develop SeqAdapt. This system streamlines data management and allows for rapid integration of novel algorithms. Our approach also allows computational biologists to focus on developing and applying new methods instead of writing boilerplate infrastructure code. The system is based around the Addama service architecture and is available at our website as a demonstration web application, an installable single download and as a collection of individual customizable services.


Influence of cigarette smoking on allergic rhinitis: a comparative study on smokers and non-smokers.
It has been described that exposure to tobacco smoke causes worsening of allergic rhinitis symptoms. Otherwise, some studies have demonstrated a negative association between cigarette smoke and allergic rhinitis (AR). Given this inconsistency, this study evaluated the quality of life and immuno-inflammatory parameters in current smokers and nonsmokers suffering from AR. A comparative cross-sectional study was conducted in patients who presented symptoms of AR. Patients were categorized into two groups: current smokers and non-smokers based on salivary cotinine measurements. Primary outcomes were the levels of immuno-inflammatory biomarkers (IgE, IL-4, IL-5, IL-13, IL-17, and IL-33) in serum and nasal lavage and the quality of life assessed by the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Secondary outcomes included salivary cotinine levels, and pulmonary function parameters, such as forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Twenty-two patients per group were included in the analysis, with no significant difference regarding demographic characteristics. Statistically significant higher values in salivary cotinine levels (p<0.001) and lower lung function FEV1 (p=0.044) and FEV1/FVC (p=0.047) were found in smokers than in nonsmokers. Only serum IL-33 was significantly different in the 2 groups (p<0.001): smokers had higher values compared to non-smokers. There were no significant differences in MiniRQLQ parameters. Although cigarette smoking was not associated with more severe symptoms, smoking could be associated with increased risk of developing airway remodeling and decreased lung function in AR patients, thus appropriate treatment should be prescribed if smoke avoidance is unfeasible.


Standards for Reporting Implementation Studies (StaRI): explanation and elaboration document.
Implementation studies are often poorly reported and indexed, reducing their potential to inform the provision of healthcare services. The Standards for Reporting Implementation Studies (StaRI) initiative aims to develop guidelines for transparent and accurate reporting of implementation studies. An international working group developed the StaRI guideline informed by a systematic literature review and e-Delphi prioritisation exercise. Following a face-to-face meeting, the checklist was developed iteratively by email discussion and critical review by international experts. The 27 items of the checklist are applicable to the broad range of study designs employed in implementation science. A key concept is the dual strands, represented as 2 columns in the checklist, describing, on the one hand, the implementation strategy and, on the other, the clinical, healthcare or public health intervention being implemented. This explanation and elaboration document details each of the items, explains the rationale and provides examples of good reporting practice. Previously published reporting statements have been instrumental in improving reporting standards; adoption by journals and authors may achieve a similar improvement in the reporting of implementation strategies that will facilitate translation of effective interventions into routine practice.


Observational study of the visibility of branded tobacco packaging and smoking at outdoor bars/cafes in Wellington, New Zealand.
To collect data on tobacco brand visibility on packaging on outdoor tables at bars/cafes in a downtown area, prior to a proposed plain packaging law. The study was conducted in the Central Business District of Wellington City in March 2014. Observational data were systematically collected on tobacco packaging visibility and smoking by patrons at 55 bars/cafes with outdoor tables. A total of 19,189 patrons, 1707 tobacco packs and 1357 active smokers were observed. One tobacco pack was visible per 11.0 patrons and the active smoking prevalence was 7.1% (95%CI: 4.9-9.2%), similar to Australian results (8.3%). Eighty percent of packs were positioned face-up (showing the brand), 8% face-down (showing the large pictorial warning), and 12% in other positions. Pack visibility per patron was significantly greater in areas without child patrons (RR=3.1, p<0.0001). Both smoking and pack visibility tended to increase from noon into the evenings on weekends. Inter-observer reliability for key measures in this study was high (Bland-Altman plots). Tobacco branding on packaging was frequently visible because of the way smokers position their packs. These results highlight the residual problem posed by this form of marketing. The results also provide baseline data for the future evaluation of plain packaging if a proposed law is implemented in New Zealand. Other results warrant further research, particularly the reasons for lower pack visibility and smoking when children were present.


Incarceration as a Health Determinant for Sexual Orientation and Gender Minority Persons.
Incarceration is considerably more prevalent among sexual and gender minority persons (SGM) than among the general population. Once behind bars, they are at the greatest risk for health-related harms. Although a growing number of studies have assessed health disparities produced by mass incarceration, scholars are yet to systematically assess the health consequences of incarceration on the basis of sexual orientation and gender identity. We invite public health scholars to study the effects of incarceration on health in the SGM population and provide a roadmap to aid these research efforts. First, we document the disproportionate presence of SGM persons in jails and prisons. Second, we note health-related risks that are the most salient for this population. Third, we recommend examining heterogeneity in the effects of incarceration by teasing out distinct risks for groups defined by sexual orientation, gender identity, and race/ethnicity. Fourth, we note methodological challenges with respect to measurement and assessing causality. Finally, we discuss the importance of health care access and quality and the need to study health during incarceration and afterward.


Whole report uncovers correctly identified but incorrectly placed target information under visual crowding.
Multiletter identification studies often find correctly identified letters being reported in wrong positions. However, how position uncertainty impacts crowding in peripheral vision is not fully understood. The observation of a flanker being reported as the central target cannot be taken as unequivocal evidence for position misperception because the observers could be biased to report a more identifiable flanker when failing to identify the central target. In addition, it has never been reported whether a correctly identified central target can be perceived at a flanker position under crowding. Empirical investigation into this possibility holds the key to demonstrating letter-level position uncertainty in crowding, because the position errors of the least identifiable central target cannot be attributed to response bias. We asked normally-sighted observers to report either the central target of a trigram (partial report) or all three characters (whole report). The results showed that, for radially arranged trigrams, the rate of reporting the central target regardless of the reported position in the whole report was significantly higher than the partial report rate, and the extra target reports mostly ended up in flanker positions. Error analysis indicated that target-flanker position swapping and misalignment (lateral shift of the target and one flanker) underlay this target misplacement. Our results thus establish target misplacement as a source of crowding errors and ascertain the role of letter-level position uncertainty in crowding.


Measurements of the middle cerebral artery in digital subtraction angiography and MR angiography.
The middle cerebral artery (MCA) has an individually varied anatomical type and course. Age and sex variability of MCA have not been completely defined. The aim was to define the range of normal values of widths and lengths of particular MCA segments, define age and sex variability, and compare the compatibility of MCA measurements of digital subtraction angiography (DSA) and MR angiography (MRA). The study was a retrospective evaluation of 114 examinations of cerebral vessels (88 DSA, 26 MRA). It included patients in whom the angiographic examinations did not show any pathological lesions. DSA was carried out using a routine protocol applied to examinations of cerebral arteries; MRA was performed with a 1.5 T scanner and the time of flight (TOF) method using the fast gradient echo sequence with RF spoiler- multivolume RF-FAST. The diameter measurements of the internal carotid arteries (ICA) and segments of the MCA were based on DSA and MRA; the study also included the lengths of MCA segments from the origin to the first first ramification and from the origin to the bifurcation. The width and length ranges of particular MCA segments in a group of healthy patients were defined by DSA and MRA. The diameters of ICA and MCA and its upper branch are age and sex dependent, being wider in men than in women and increasing with age. MR angiography is a fully reliable method allowing assessment of middle artery morphology, but precise evaluation of the widths of the artery and arterial branches with MRA should include the source images of the vascular sequence.


Chemopreventive effect of myrtenal on bacterial enzyme activity and the development of 1,2-dimethyl hydrazine-induced aberrant crypt foci in Wistar Rats.
Colon cancer remains as a serious health problem around the world despite advances in diagnosis and treatment. Dietary fibers are considered to reduce the risk of colon cancer as they are converted to short chain fatty acids by the presence of anaerobic bacteria in the intestine, but imbalanced diet and high fat consumption may promote tumor formation at different sites, including the large bowel via increased bacterial enzymes activity. The present study was conducted to characterize the inhibitory action of myrtenal on bacterial enzymes and aberrant crypt foci (ACF). Experimental colon carcinogenesis induced by 1,2-dimethylhydrazine is histologically, morphologically, and anatomically similar to human colonic epithelial neoplasm. Discrete microscopic mucosal lesions such as ACF and malignant tumors function as important biomarkers in the diagnosis of colon cancer. Methylene blue staining was carried out to visualize the impact of 1,2-dimethylhydrazine and myrtenal. Myrtenal-treated animals showed decreased levels of bacterial enzymes such as β-glucuronidase, β-glucosidase, and mucinase. Characteristic changes in the colon were noticed by inhibiting ACF formation in the colon. In conclusion, treatment with myrtenal provided altered pathophysiological condition in colon cancer-bearing animals with evidence of decreased crypt multiplicity and tumor progression.


Soil-transmitted helminthiasis: A neglected tropical disease among urban slum dwelling school-aged children of a sub-Saharan African city.
The need to generate a robust epidemiological data on the neglected tropical diseases is imperative, in order to encourage access to formal care, drive public policies and ensure the allocation of resources by policy-makers. The objective of this study was to determine the prevalence of soil-transmitted helminthiasis (STH) and its association with nutritional variables among primary school pupils living in urban slums in a South-Eastern sub-Saharan African city of Enugu, Nigeria. The stool samples of school-aged children living in urban slums were analyzed for ova of the helminths using the Kato-Katz methods, whereas the nutritional assessment (weight and height) was obtained and analyzed to indicate acute or chronic malnutrition. Degrees of helminthic load were then classified. The socioeconomic status was determined while the prevalence of STH and the relationship between it and the nutritional stratus was assessed to ascertain any significance between being malnourished and having STH as this will inform policy decisions. There were a total of 371 analyzed stool samples from 228 females (61.5%) and 143 males (38.5%), with 285 (76.8%) from the lowest socioeconomic class. The prevalence of STH was 18.1%, while that of acute and chronic malnutrition were 3.3% and 7.5%, respectively. The intensity of infestation was, however, light, with the highest mean egg intensity of 74.4 ± 32.8 documented for ascariasis. There was no statistically significant association between the presence of STH and various indices of acute and chronic malnutrition (P > 0.05). STHs prevalence is high among children living in urban slums. Nutritional status was, however, not adversely affected by helminthic infestation.


Protein phosphatase type 1 interacts with proteins required for meiosis and other cellular processes in Saccharomyces cerevisiae.
Protein phosphatase type I (PP1) is involved in diverse cellular processes, and its activity toward specific substrates is thought to be controlled by different regulatory or targeting subunits. To identify regulatory subunits and substrates of the Saccharomyces cerevisiae PP1, encoded by GLC7, we used the two-hybrid system to detect interacting proteins. Among the many proteins identified were Gac1, a known glycogen regulatory subunit, and a protein with homology to Gac1. We also characterized a new gene designated GIP1, for Glc7-interacting protein. We show that a Gip1 fusion protein coimmunoprecipitates with PP1 from cell extracts. Molecular and genetic analyses indicate that GIP1 is expressed specifically during meiosis, affects transcription of late meiotic genes, and is essential for sporulation. Thus, the Gip1 protein is a candidate for a meiosis-specific substrate or regulator of PP1. Finally, we recovered two genes, RED1 and SCD5, with roles in meiosis and the vesicular secretory pathway, respectively. These results provide strong evidence implicating PP1 function in meiosis. In addition, this study indicates that the two-hybrid system offers a promising approach to understanding the multiple roles and interactions of PP1 in cellular regulation.


Human action recognition in videos using kinematic features and multiple instance learning.
We propose a set of kinematic features that are derived from the optical flow for human action recognition in videos. The set of kinematic features includes divergence, vorticity, symmetric and antisymmetric flow fields, second and third principal invariants of flow gradient and rate of strain tensor, and third principal invariant of rate of rotation tensor. Each kinematic feature, when computed from the optical flow of a sequence of images, gives rise to a spatiotemporal pattern. It is then assumed that the representative dynamics of the optical flow are captured by these spatiotemporal patterns in the form of dominant kinematic trends or kinematic modes. These kinematic modes are computed by performing Principal Component Analysis (PCA) on the spatiotemporal volumes of the kinematic features. For classification, we propose the use of multiple instance learning (MIL) in which each action video is represented by a bag of kinematic modes. Each video is then embedded into a kinematic-mode-based feature space and the coordinates of the video in that space are used for classification using the nearest neighbor algorithm. The qualitative and quantitative results are reported on the benchmark data sets.


Leishmaniasis in immunosuppressed individuals.
Leishmaniasis is a vector-born chronic infectious disease caused by a group of protozoan parasites of the genus Leishmania. Whereas most immunocompetent individuals will not develop disease after Leishmania infection, immunosuppression is a well-established risk factor for disease. The most severe form is visceral leishmaniasis (VL), which is typically fatal if untreated. Whereas human immunodeficiency virus (HIV) co-infection (VL-HIV) was initially mainly reported from southern Europe, it is now emerging in other regions, including East Africa, India, and Brazil. VL has also been found in a wide range of non-HIV-related immunosuppressive states, mainly falling under the realm of transplantation medicine, rheumatology, haematology, and oncology. Clinical presentation can be atypical in immunosuppressed individuals, being easily misdiagnosed or mistaken as a flare-up of the underlying disease. The best diagnostic approach is the combination of parasitological and serological or molecular methods. Liposomal amphotericin B is the drug of choice. Treatment failure and relapse rates are particularly high in cases of HIV co-infection, despite initiation of antiretroviral treatment. Primary prophylaxis is not recommended, but secondary prophylaxis is recommended when the patient is immunosuppressed. Cutaneous leishmaniasis can have a number of particular features in individuals with immunosuppression, especially if severe, including parasite dissemination, clinical polymorphism with atypical and often more severe clinical forms, and even visceralization. Mucosal leishmaniasis is more common. Treatment of cutaneous and mucosal leishmaniasis can be challenging, and systemic treatment is more often indicated. With globally increased travel and access to advanced medical care in developing countries, the leishmaniasis burden in immunosuppressed individuals will probably continue to rise, warranting increased awareness and enhanced surveillance systems.


Response of chlorophyll a to total nitrogen and total phosphorus concentrations in lotic ecosystems: a systematic review protocol.
Eutrophication of freshwater ecosystems resulting from nitrogen and phosphorus pollution is a major stressor across the globe. Despite recognition by scientists and stakeholders of the problems of nutrient pollution, rigorous synthesis of scientific evidence is still needed to inform nutrient-related management decisions, especially in streams and rivers. Nutrient stressor-response relationships are complicated by multiple interacting environmental factors, complex and indirect causal pathways involving diverse biotic assemblages and food web compartments, legacy (historic) nutrient sources such as agricultural sediments, and the naturally high spatiotemporal variabilityof lotic ecosystems. Determining nutrient levels at which ecosystems are affected is a critical first step for identifying, managing, and restoring aquatic resources impaired by eutrophication and maintaining currently unimpaired resources. The systematic review outlined in this protocol will compile and synthesize literature on the response of chlorophyll a to nutrients in streams, providing a state-of-the-science body of evidence to assess nutrient impacts to one of the most widely-used measures of eutrophication. This review will address two questions: "What is the response of chlorophyll a to total nitrogen and total phosphorus concentrations in lotic ecosystems?" and "How are these relationships affected by other factors?" Searches for published and unpublished articles (peer-reviewed and non-peer-reviewed) will be conducted using bibliographic databases and search engines. Searches will be supplemented with bibliography searches and requests for material from the scientific and management community. Articles will be screened for relevance at the title/abstract and full text levels using pre-determined inclusion criteria; 10% (minimum 50, maximum 200) of screened papers will be examined by multiple reviewers to ensure consistent application of criteria. Study risk of bias will be evaluated using a questionnaire developed from existing frameworks and tailored to the specific study types this review will encounter. Results will be synthesized using meta-analysis of correlation coefficients, as well as narrative and tabular summaries, and will focus on the shape, direction, strength, and variability of available nutrient-chlorophyll relationships. Sensitivity analysis and meta-regression will be used to evaluate potential effects of study quality and modifying factors on nutrient-chlorophyll relationships.


Airway Management in the Prehospital, Combat Environment: Analysis of After-Action Reviews and Lessons Learned.
Airway compromise is the second leading cause of potentially survivable death on the battlefield. Studies show that airway management is a challenge in prehospital combat care with high error and missed opportunity rates. Lacking is user information on the perceived reasons for the challenges. The US military uses several performance improvement and field feedback systems to solicit feedback regarding deployed experiences. We seek to review feedback and after-action reviews (AARs) from end-users with specific regard to airway challenges noted. We queried the Center for Army Lessons Learned (CALL), the Army Medical Department Lessons Learned (AMEDDLL), and the Joint Lessons Learned Information System (JLLIS).Our queries comprised a series of search terms with a focus on airway management. Three military emergency medicine expert reviewers performed the primary analysis for lessons learned specific to deployment and predeployment training lessons learned. Upon narrowing the scope of entries to those relevant to deployment and predeployment training, a panel of eight experts performed reviews. The varied nature of the sources lent itself to an unstructured qualitative approach with results tabulated into thematic categories. Our initial search yielded 611 nonduplicate entries. The primary reviewers then analyzed these entries to determine relevance to the project-this resulted in 70 deployment- based lessons learned and four training-based lessons learned. The panel of eight experts then reviewed the 74 lessons learned. We categorized 37 AARs as equipment challenges/malfunctions, 28 as training/education challenges, and 9 as other. Several lessons learned specifically stated that units failed to prioritize medic training; multiple comments suggested that units should consider sending their medics to civilian training centers. Other comments highlighted equipment shortages and equipment malfunctions specific to certain mission types (e.g., pediatric casualties, extreme weather). In this review of military lessons learned systems, most of the feedback referenced equipment malfunctions and gaps in initial and maintenance training.This review of AARs provides guidance for targeted research efforts based the needs of the end-users.


Room temperature stable CO x -free H2 production from methanol with magnesium oxide nanophotocatalysts.
Methanol, which contains 12.6 weight percent hydrogen, is a good hydrogen storage medium because it is a liquid at room temperature. However, by releasing the hydrogen, undesirable CO and/or CO2 byproducts are formed during catalytic fuel reforming. We show that alkaline earth metal oxides, in our case MgO nanocrystals, exhibit stable photocatalytic activity for CO/CO2-free H2 production from liquid methanol at room temperature. The performance of MgO nanocrystals toward methanol dehydrogenation increases with time and approaches ~320 μmol g-1 hour-1 after a 2-day photocatalytic reaction. The CO x -free H2 production is attributed to methanol photodecomposition to formaldehyde, photocatalyzed by surface electronic states of unique monodispersed, porous MgO nanocrystals, which were synthesized with a novel facile colloidal chemical strategy. An oxygen plasma treatment allows for the removal of organic surfactants, producing MgO nanocrystals that are well dispersible in methanol.


Liver abscess after non-operative management of blunt liver injury.
The non-operative management of blunt liver trauma can be applied in almost 80% of patients with this type of injury, with the advantages of the need for fewer blood transfusions, less intra-abdominal sepsis, and a better survival rate, than with the operative approach. However, liver abscess, as a known complication of the non-operative management of blunt liver trauma, is discussed infrequently. Therefore, we herein review our experience and describe this complication in detail. From 1995 to 2001, 674 patients were admitted to our hospital due to blunt hepatic trauma. Among these patients, 279 underwent laparotomy and the remaining 395 patients were treated non-operatively. Twenty-two patients were identified as having liver abscess, with 16 of them belonging to the operative group, and six to the non-operative group. A retrospective review of these six patients and their characteristics, as well as pathogenesis, diagnosis, and the management of the liver abscesses, was conducted. These six patients were all male, with a median age of 19.5 years (range 3-24). The median injury severity score was 16.5 (range 9-25); three patients sustained grade-3 hepatic injury, and the other three were grade 4. The main diagnostic tool was abdominal computed tomography, and the abscesses took a median of 6 days (range 1-12) to form and be diagnosed. The abscesses were usually caused by infection from mixed organisms, and an abscess resulting from Clostridium infection developed within 1 day after injury. These abscesses were treated with antibiotics and drainage, and the median length of hospital stay was 26 days (range 8-44), without mortality or long-term morbidity. Liver abscess as a complication of the non-operative management of blunt hepatic trauma is a rare entity, with an incidence of 1.5% (6/395). It is usually seen in severe liver injury (grade 3 and above), but all our patients were all treated successfully, with no mortality. However, prolonged hospitalization may be required in this patient group.


The impact of COVID-19 on the cancer care of adolescents and young adults and their well-being: Results from an online survey conducted in the early stages of the pandemic.
Because of the global spread of coronavirus disease 2019 (COVID-19), oncology departments across the world have rapidly adapted their cancer care protocols to balance the risk of delaying cancer treatments and the risk of COVID-19 exposure. COVID-19 and associated changes may have an impact on the psychosocial functioning of patients with cancer and survivors. This study was designed to determine the impact of the COVID-19 pandemic on young people living with and beyond cancer. In this cross-sectional study, 177 individuals, aged 18 to 39 years, were surveyed about the impact of COVID-19 on their cancer care and psychological well-being. Participants also reported their information needs with respect to COVID-19. Responses were summarized with a content analysis approach. This was the first study to examine the psychological functioning of young patients and survivors during the first weeks of the COVID-19 pandemic. A third of the respondents reported increased levels of psychological distress, and as many as 60% reported feeling more anxious than they did before COVID-19. More than half also wanted more information tailored to them as young patients with cancer. The COVID-19 pandemic is rapidly evolving and changing the landscape of cancer care. Young people living with cancer are a unique population and might be more vulnerable during this time in comparison with their healthy peers. There is a need to screen for psychological distress and attend to young people whose cancer care has been delayed. As the lockdown begins to ease, the guidelines about cancer care should be updated according to this population's needs.


Comparison of Signaling Pathways Gene Expression in CD34(-) Umbilical Cord Blood and Bone Marrow Stem Cells.
The aim of the study was to compare the biological activity of the total pool of genes in CD34(-) umbilical cord blood and bone marrow stem cells and to search for the differences in signaling pathway gene expression responsible for the biological processes. The introductory analysis revealed a big similarity of gene expression among stem cells. When analyzing GO terms for biological processes, we observed an increased activity of JAK-STAT signaling pathway, calcium-mediated, cytokine-mediated, integrin-mediated signaling pathway, and MAPK in a cluster of upregulating genes in CD34(-) umbilical cord blood stem cells. At the same time, we observed a decreased activity of BMP signaling pathways, TGF-beta pathway, and VEGF receptor signaling pathway in a cluster of downregulating genes in CD34(-) umbilical cord blood stem cells. In accordance with KEGG classification, the cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, and JAK-STAT signaling pathway are overrepresented in CD34(-) umbilical cord blood stem cells. A similar gene expression in both CD34(-) UCB and BM stem cells was characteristic for such biological processes as cell division, cell cycle gene expression, mitosis, telomere maintenance with telomerase, RNA and DNA treatment processes during cell division, and similar genes activity of Notch and Wnt signaling pathways.


Orthohalogen substituents dramatically enhance hydrogen bonding of aromatic ureas in solution.
The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry. Here we report that the introduction of chlorine or bromine atoms in the ortho positions to the urea unit is a simple and very efficient way to improve its intermolecular hydrogen bond (HB) donor character. This effect was demonstrated in solution both in the context of self-association of bis-ureas and hydrogen bonding of mono-ureas to strong HB acceptors.


Absolute configuration, stability, and interconversion of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine valine adducts and their phenylthiohydantoin derivatives.
Pyrrolizidine alkaloid-containing plants are widespread in the world and probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolic activation to form dehydropyrrolizidine alkaloids that bind to cellular proteins and DNA leading to hepatotoxicity, genotoxicity, and tumorigenicity. At present, it is not clear how dehydropyrrolizidine alkaloids bind to cellular amino acids and proteins to induced toxicity. We previously reported that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts that upon reaction with phenyl isothiocyanate (PITC) formed four DHP-valine-PITC adduct isomers. In this study, we report the absolute configuration and stability of DHP-valine and DHP-valine-PITC adducts, and the mechanism of interconversion between DHP-valine-PITC adducts.


Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016).
There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1-16). Adverse events were similar to those known for this combination. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study's target response rate and is not considered active in refractory MPNST.


Zeitgebers and their association with rest-activity patterns.
Zeitgebers such as light, eating and physical activity provide input to the circadian clock. Chronic circadian misalignment is associated with significant adverse health effects. An improved understanding of the impact of the timing of zeitgebers on the stability of 24-hour rest-activity rhythm in free-living settings may identify behavioural and environmental intervention targets. A total of 133 healthy adults, aged 21-60 years, wore a wrist actigraph for 7 consecutive days. We applied a non-parametric analysis to activity counts to derive rest-activity patterns. We administered a questionnaire through a smartphone app to collect self-reported timing of light exposure, eating episodes and physical activity. To assess the relationship between timing exposures (first and last exposure to outdoor light, first exposure to indoor light, last eating episode, first eating episode, morning physical activity proportion, evening physical activity proportion) and rest-activity or sleep outcomes (bedtimes, total sleep time, inter-daily stability, intra-daily variability, L5 and M10 midpoint), we first calculated Spearman correlations, using the false discovery rate method to control for multiple comparisons. From those significant associations, we then fit regression models adjusting for age, sex, race, household income, education level, study site, body mass index, as well as physical activity. Finally, we tested for interaction between chronotype and each timing-related exposure and stratified the analysis by morning type. All zeitgebers, except for evening physical activity proportion, were correlated with at least four of the seven sleep and rest-activity outcomes. In adjusted analysis, later timing of first (after 6:30 to 7:45 AM versus earlier) and last exposure to indoor light (after 11:00 PM versus earlier) and first (after 7:45-9:45 AM versus earlier) and last eating episode (after 8:00-09:00 PM versus earlier) were associated with a shift of 0.60-1.39 hours to later bedtimes, M10 and L5 midpoints (i.e. timing of peak activities or inactivities). Later timing of first exposure to outdoor light (after 09:30 AM versus earlier) was also associated with 0.51 (95% CI: 0.19 to 0.83) hours longer total sleep time. Higher morning physical activity proportion (> 33%) was associated with 0.95 (95% CI: -1.38 to -0.53) hours earlier in-bed time and 0.69 (95% CI: -1.14 to -0.24) hours earlier out-of-bed time, 0.92 (95% CI: -1.41 to -0.42) hours earlier M10 and 0.96 (95% CI: -1.42 to -0.49) min earlier L5 midpoint. The results did not change substantially with further adjustment for total activity. There was a significant interaction between morning chronotype and first eating episode with rest-activity patterns (p < 0.05), with first eating episode associating with timing of activities only in non-morning type adults. Timing of zeitgebers was associated with sleep and rest-activity patterns, including bedtimes, L5 and M10 midpoint. Future research should evaluate the impact of manipulating zeitgebers on both circadian rhythms and health outcomes.


Cytokine profiles in adult mink infected with Aleutian mink disease parvovirus.
The aim of this study was to examine the levels of gamma interferon (IFN-gamma)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8(+)) cells in the blood during the infection. We quantified the percentages of IFN-gamma- and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-gamma- and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-gamma and IL-4 in ADV-infected mink was produced by CD8(+) cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1- and Th2-driven immune functions are found in mink plasmacytosis.


Neurocognitive and observational markers: prediction of autism spectrum disorder from infancy to mid-childhood.
Prospective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age. However, some diagnostic changes occur between toddlerhood and mid-childhood, which raises the question of whether infant markers remain associated with diagnosis into mid-childhood. First, we tested whether infant neurocognitive markers (7-month neural response to eye gaze shifts and 14-month visual disengagement latencies) as well as an observational marker of emerging ASD behaviours (the Autism Observation Scale for Infants; AOSI) predicted ASD outcome in high-risk (HR) 7-year-olds with and without an ASD diagnosis (HR-ASD and HR-No ASD) and low risk (LR) controls. Second, we tested whether the neurocognitive markers offer predictive power over and above the AOSI. Both neurocognitive markers distinguished children with an ASD diagnosis at 7 years of age from those in the HR-No ASD and LR groups. Exploratory analysis suggested that neurocognitive markers may further differentiate stable versus lost/late diagnosis across the 3 to 7 year period, which will need to be tested in larger samples. At both 7 and 14 months, combining the neurocognitive marker with the AOSI offered a significantly improved model fit over the AOSI alone. Infant neurocognitive markers relate to ASD in mid-childhood, improving predictive power over and above an early observational marker. The findings have implications for understanding the neurodevelopmental mechanisms that lead from risk to disorder and for identification of potential targets of pre-emptive intervention.


Nosocomial Pseudomonas pickettii bacteremias traced to narcotic tampering. A case for selective drug screening of health care personnel.
Three patients in a university hospital developed nosocomial infusion-related Pseudomonas pickettii bacteremia. Investigation identified six additional patients who had received intravenous fluid contaminated by P pickettii but did not become ill. All nine patients had had surgery, and each of these patients but only nine of 19 operated-on control patients had received intravenous fentanyl citrate in the operating room; the mean dose given to the nine case patients was far greater than that given to control patients. Fentanyl in 20 (40%) of 50 predrawn 30-mL syringes was shown to be contaminated by P pickettii. Contamination was caused by theft of fentanyl from predrawn synringes and replacement by distilled water contaminated by P pickettii. Narcotic theft by health care personnel may cause patients to suffer pain needlessly and can also result in dire unanticipated consequences, such as nosocomial bacteremia. Whereas drug testing in the workplace is highly controversial, we believe that testing of health care personnel is indicated when drug abuse or theft is suspected.


A systematic map of genetic variation in Plasmodium falciparum.
Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified approximately 500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs.


Global minimum structure search in Li(x)CoO2 composition using a hybrid evolutionary algorithm.
The global minimum structures for Li(x)CoO(2) compositions where 0 ≤ x ≤ 1 were probed by using a hybrid evolutionary algorithm with an underlying ab initio structural relaxation scheme. The method successfully predicted experimentally observed variants of layered configurations at various degrees of lithiation and the spinel (Fd3[combining macron]m) phase at x = 1/2. New low-energy non-layered host structures at x < 1/2 were also revealed. These structures can be formed from the usual layered configuration through coherent stacking faults along the c-axis and the migration of Co ions into the Li-poor intercalation layer.