Chimpanzees are rational maximizers in an ultimatum game.
Traditional models of economic decision-making assume that people are self-interested rational maximizers. Empirical research has demonstrated, however, that people will take into account the interests of others and are sensitive to norms of cooperation and fairness. In one of the most robust tests of this finding, the ultimatum game, individuals will reject a proposed division of a monetary windfall, at a cost to themselves, if they perceive it as unfair. Here we show that in an ultimatum game, humans' closest living relatives, chimpanzees (Pan troglodytes), are rational maximizers and are not sensitive to fairness. These results support the hypothesis that other-regarding preferences and aversion to inequitable outcomes, which play key roles in human social organization, distinguish us from our closest living relatives.


Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines.
Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.


Maternal Mortality Reports-Case 4, C.M.A. Committee on Maternal and Child Care.
These case reports are taken from the files of the State Department of Public Health which, together with the California Medical Association, now sponsors the statewide studies of all maternal mortalities. Selected cases are here presented from time to time as a matter of interest and illumination to all physicians concerned with the practice of obstetrics. They are prepared by the Committee on Maternal and Child Care. It is hoped that a review of such significant cases will help to improve the welfare of future California mothers.


Intravascular photoacoustic imaging at 35 and 80 MHz.
The catheter-based intravascular photoacoustic (IVPA) imaging for diagnosing atherosclerosis, which can provide optical absorption contrast of the arterial wall besides acoustic scattering contrast from the conventional intravascular ultrasound (IVUS) imaging, has been intensively researched recently. The resolution of IVPA is determined by the frequency bandwidth of an ultrasonic transducer. Higher resolution can be achieved by increasing the transducer's working frequency and bandwidth. We introduce IVPA imaging at 35 and 80 MHz by using newly designed integrated IVUS/IVPA probes. This is the first time IVPA has been achieved as high as 80 MHz. Six-micrometer tungsten wires were imaged to evaluate the probes' spatial resolutions and beam patterns. Healthy rabbit aorta was imaged in vitro. Imaging results show that IVPA has superior contrast over IVUS in identifying the arterial wall, and IVPA at 80 MHz demonstrates extraordinary resolution (35 μm) compared to 35 MHz.


Severe Behçet's disease equally affects both genders in Egyptian patients: A multicentre retrospective follow-up study.
Behçet's disease is a relapsing multisystemic disease. Its highest prevalence is seen along the Silk Road. While several studies reported gender disparities, others didn't. Scarce data are available about the Arabs and the gender differences detected in some ethnicities could not be applied to others. Our study aimed to detect gender differences among a cohort of adult Egyptian patients with Behçet's disease. Medical files of 255 adult patients diagnosed with Behçet's disease at the Rheumatology and Rehabilitation Department of Kasr Al-Aini Hospital, Cairo University and the Internal Medicine Department of Tanta University, between 2002 and 2018, were retrospectively reviewed. The demographic features, the cumulative clinical features, the use, if any, of an intravenous pulse of methylprednisolone and immunosuppressive/biological drugs, and the frequency of the cumulative damage to the different organ systems were described. The disease severity score was calculated as well. The study revealed a prominent male predominance; the male to female ratio was 6.7:1. Acne/pseudofolliculitis was more common in males (28.6% vs 13.2%, p=0.046); the same was observed regarding any vascular involvement and peripheral venous disease (36.3% vs 18.4%, p=0.03 and 30.4% vs 13.2%, p=0.03, respectively). On the other hand, encephalitis and cranial nerve lesions were more prevalent in females (15.8% vs 6%, p=0.03 and 10.5% vs 3.2%, p=0.04, respectively). Severe Behçet's disease equally affects Egyptian males and females. BD should not be considered a benign disease in Egyptian females. The same quality of medical care should be equally offered to both genders.


Using Pseudocontact Shifts and Residual Dipolar Couplings as Exact NMR Restraints for the Determination of Protein Structural Ensembles.
Nuclear magnetic resonance (NMR) spectroscopy provides detailed information about the structure and dynamics of proteins by exploiting the conformational dependence of the magnetic properties of certain atomic nuclei. The mapping between NMR measurements and molecular structures, however, often requires approximated descriptions based on the fitting of a number of parameters, thus reducing the quality of the information available from the experiments. To improve on this limitation, we show here that it is possible to use pseudocontact shifts and residual dipolar couplings as "exact" NMR restraints. We implement this strategy by using a replica-averaging method and illustrate its application by calculating an ensemble of structures representing the dynamics of the two-domain protein calmodulin.


Comparison of analyses of the QTLMAS XIII common dataset. I: genomic selection.
Genomic selection, the use of markers across the whole genome, receives increasing amounts of attention and is having more and more impact on breeding programs. Development of statistical and computational methods to estimate breeding values based on markers is a very active area of research. A simulated dataset was analyzed by participants of the QTLMAS XIII workshop, allowing a comparison of the ability of different methods to estimate genomic breeding values. A best case scenario was analyzed by the organizers where QTL genotypes were known. Participants submitted estimated breeding values for 1000 unphenotyped individuals together with a description of the applied method(s). The submitted breeding values were evaluated for correlation with the simulated values (accuracy), rank correlation of the best 10% of individuals and error in predictions. Bias was tested by regression of simulated on estimated breeding values. The accuracy obtained from the best case scenario was 0.94. Six research groups submitted 19 sets of estimated breeding values. Methods that assumed the same variance for markers showed accuracies, measured as correlations between estimated and simulated values, ranging from 0.75 to 0.89 and rank correlations between 0.58 and 0.70. Methods that allowed different marker variances showed accuracies ranging from 0.86 to 0.94 and rank correlations between 0.69 and 0.82. Methods assuming equal marker variances were generally more biased and showed larger prediction errors. The best performing methods achieved very high accuracies, close to accuracies achieved in a best case scenario where QTL genotypes were known without error. Methods that allowed different marker variances generally outperformed methods that assumed equal marker variances. Genomic selection methods performed well compared to traditional, pedigree only, methods; all methods showed higher accuracies than those obtained for breeding values estimated solely on pedigree relationships.


A cluster randomised controlled trial of nurse and GP partnership for care of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a significant health problem worldwide. This randomised controlled trial aims at testing a new approach that involves a registered nurse working in partnership with patients, general practitioners (GPs) and other health professionals to provide care to patients according to the evidence-based clinical practice guidelines. The aim is to determine the impact of this partnership on the quality of care and patient outcomes. A cluster randomised control trial design was chosen for this study. Randomisation occurred at practice level. GPs practising in South Western Sydney, Australia and their COPD patients were recruited for the study.The intervention was implemented by nurses specifically recruited and trained for this study. Nurses, working in partnership with GPs, developed care plans for patients based on the Australian COPDX guidelines. The aim was to optimise patient management, improve function, prevent deterioration and enhance patient knowledge and skills. Control group patients received 'usual' care from their GPs. Data collection includes patient demographic profiles and their co-morbidities. Spirometry is being performed to assess patients' COPD status and CO analyser to validate their smoking status. Patients' quality of life and overall health status are being measured by St George's Respiratory Questionnaire and SF-12 respectively. Other patient measures being recorded include health service use, immunisation status, and knowledge of COPD. Qualitative methods will be used to explore participants' satisfaction with the intervention and their opinion about the value of the partnership. Analysis will be by intention to treat. Intra-cluster (practice) correlation coefficients will be determined and published for all primary outcome variables to assist future research. The effect of the intervention on outcomes measured on a continuous scale will be estimated and tested using mixed model analysis of variance in which time and treatment group will be fixed effects and GP practice and subject nested within practice will be random effects. The effect of the intervention on the dichotomous variables (such as smoking status, patient knowledge) will be analysed using generalised estimating equations with a logistic link and a model structure that is analogous to that described above. ACTRN012606000304538.


Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes.
Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins.


Immunological impact of Taekwondo competitions.
Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (p<0.05, respectively). Natural killer cells increased immediately after the competitions (p=0.0006), and decreased during recovery. B and T cells increased immediately after the competitions and remained elevated throughout recovery (p<0.05, respectively). CD4/CD8 ratio after the competitions was decreased (p=0.0091) and returned to baseline during recovery. These results suggest that the immunological function of the elite female adolescent athletes could be attenuated after Taekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes.


Relief from Zmp1-mediated arrest of phagosome maturation is associated with facilitated presentation and enhanced immunogenicity of mycobacterial antigens.
Pathogenic mycobacteria escape host innate immune responses by blocking phagosome-lysosome fusion. Avoiding lysosomal delivery may also be involved in the capacity of mycobacteria to evade major histocompatibility complex (MHC) class I- or II-dependent T-cell responses. In this study, we used a genetic mutant of Mycobacterium bovis BCG that is unable to escape lysosomal transfer and show that presentation of mycobacterial antigens is affected by the site of intracellular residence. Compared to infection with wild-type BCG, infection of murine bone marrow-derived dendritic cells with a mycobacterial mutant deficient in zinc metalloprotease 1 (Zmp1) resulted in increased presentation of MHC class II-restricted antigens, as assessed by activation of mycobacterial Ag85A-specific T-cell hybridomas. The zmp1 deletion mutant was more immunogenic in vivo, as measured by delayed-type hypersensitivity (DTH), antigen-specific lymphocyte proliferation, and the frequency of antigen-specific gamma interferon (IFN-γ)-producing lymphocytes of both CD4 and CD8 subsets. In conclusion, our results suggest that phagosome maturation and lysosomal delivery of BCG facilitate mycobacterial antigen presentation and enhance immunogenicity.


Unraveling the human salivary microbiome diversity in Indian populations.
The importance of studying the salivary microbiome has been highlighted for its connection to health and disease and as a potential tool for supplementing human genetic diversity studies. While the salivary microbiome has been studied in various world populations, Indian populations have not been examined. We therefore analyzed microbiome diversity in saliva samples from 92 volunteers from eight different sampling locations in India by amplifying and sequencing variable regions (V1 and V2) of the bacterial 16S rRNA gene. The results showed immense bacterial richness in Indian populations; we identified 165 bacterial genera and 785 unique Operational Taxonomic Units (OTUs), with substantial sharing among the populations. There were small, but significant correlations in the abundance of bacterial genera in sampling locations from the same geographic region. Most of the core OTUs detected were also observed previously in other populations, but Solobacterium spp., Lachnoanaerobaculum spp. and Alloprevotella spp. were observed to be a component of the saliva microbiome unique to Indian populations. Importantly, nine bacterial genera were observed that were not listed in the Human Oral Microbiome Database (HOMD). These results highlight the importance of analyzing underrepresented populations like those of India.


Motivations and challenges of community-based surveillance volunteers in the northern region of Ghana.
Community health workers (CHWs) are an important element of many health systems and programmes for the promotion and delivery of a wide range of health interventions and disease surveillance. Understanding the motivation and retention of CHWs is recognized as essential but there are few data from sub-Saharan Africa. This qualitative study explored factors that motivate, and the challenges faced by community-based surveillance volunteers (CBSVs) in the Northern Region of Ghana through semi-structured interviews with 28 CBSVs, 12 zonal coordinators, nine Ghana Health Service (GHS) sub-district level staff, ten GHS district level staff and two GHS regional level staff in the administrative capital. The community emerged as an important motivating factor in terms of altruism, a sense of duty to the community and gaining community respect and pride. This was enhanced by community selection of the volunteers. Major challenges included incorrect community perceptions of CBSVs, problems with transportation and equipment, difficulties conducting both volunteer and farm work and late or lack of payment for ad hoc tasks such as National Immunization Days. Most CBSVs recognized that they were volunteers, understood the constraints of the health system and were not demanding remuneration. However, CBSVs strongly desired something tangible to show that their work is recognized and appreciated and described a number of low cost items that could be used. They also desired equipment such as raincoats and identifiers such as tee-shirts and certificates.


Tumor necrosis factor alpha gene G-308A polymorphism, insulin resistance, and fasting plasma glucose in young, older, and diabetic Japanese men.
In obese subjects, the levels of tumor necrosis factor alpha (TNF-alpha) expression and protein synthesis in adipocytes are increased. A recent study of Caucasians suggested that the TNF-alpha gene promoter region polymorphism at position -308 influences insulin resistance and percent body fat and increases serum leptin levels, although conflicting data are also reported. The present study was performed to investigate the relationship between this polymorphism and the body mass index (BMI), blood pressure, glucose and lipid profiles, and serum leptin in 122 healthy young men aged 21 to 29, 177 older men aged 45 to 65, and 71 type 2 diabetic male patients aged 42 to 78. The BMI, blood pressure, and fasting plasma glucose (FPG), serum lipids, uric acid, insulin, and leptin concentrations were measured. The TNF-alpha G-308A polymorphism was assessed by the polymerase chain reaction restriction fragment length polymorphism method. In the young group, 4 subjects (3.3%) were heterozygous for the TNF2 (G-308A-positive) allele, but there were no significant differences between the TNF1 (wild-type) and TNF2 groups in any measured anthropometric or metabolic parameter. In the older group, the frequency of the TNF2 group was 2.8%, and FPG was significantly higher in the TNF2 versus the TNF1 group (108 +/- 7 v 99 +/- 9 mg/dL, P= .042 by Mann-Whitney Utest). Plasma triglycerides and the insulin resistance index tended to be higher and high-density lipoprotein (HDL) cholesterol tended to be lower in the TNF2 group (P = .06, .20, and .07, respectively), although these differences were not statistically significant. In type 2 diabetic subjects, the frequency of the TNF2 group was also 2.8%, and there were no significant differences between the TNF1 and TNF2 groups in any parameter. HDL cholesterol tended to be lower (P = .10) in the TNF2 group, although it was not statistically significant. In conclusion, no major difference was associated with TNF1 and TNF2 polymorphisms in terms of obesity, blood pressure, lipids, or glucose in young, older, or diabetic Japanese men, although FPG was significantly higher in older men, possibly through increased insulin resistance.


Collagen-based structures containing the peptoid residue N-isobutylglycine (Nleu): synthesis and biophysical studies of Gly-Pro-Nleu sequences by circular dichroism, ultraviolet absorbance, and optical rotation.
A peptoid residue N-isobutylglycine (Nleu) was introduced as a proline surrogate in collagen-like triple helical structures. A series of single chain and template-assembled collagen-based peptide-peptoid structures composed of Gly-Pro-Nleu sequences were prepared by solid-phase segment condensation methods. Both a synthetic route in solution and a solid phase method were employed to couple the KTA (cis,cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid, also known as the Kemp triacid) based template, KTA-(Gly-OH)3, to peptide-peptoid chains. Biophysical studies using CD, uv absorbance, and optical rotation measurements demonstrated that these compounds form triple-helical structures when the chains are longer than critical lengths. Results from melting curve measurements indicated that the Gly-Pro-Nleu sequence is comparable to the Gly-Pro-Pro sequence in stabilizing a triple-helical conformation. The KTA-based template stabilized triple-helical structures as can be seen by the increased melting temperatures as compared to equivalent single chain molecules. In addition, the template reduced the minimum chain length necessary to form a triple helix from six to only three trimer repeats.


A multidisciplinary team care approach improves outcomes in high-risk pediatric neuroblastoma patients.
We assessed the impact of a multidisciplinary team care program on treatment outcomes in neuroblastoma patients. Newly diagnosed neuroblastoma patients received treatment under the Taiwan Pediatric Oncology Group (TPOG) N2002 protocol at the National Taiwan University Hospital beginning in 2002. A multidisciplinary team care approach that included nurse-led case management for patients treated under this protocol began in January 2010. Fifty-eight neuroblastoma patients, including 29 treated between 2002 and 2009 (Group 1) and 29 treated between 2010 and 2014 (Group 2), were enrolled in the study. The 5-year overall survival (OS) and event-free survival (EFS) rates for all 58 patients were 59% and 54.7%, respectively. Group 2 patients, who were treated after implementation of the multidisciplinary team care program, had better 3-year EFS (P = 0.046), but not OS (P = 0.16), rates than Group 1 patients. In a multivariate analysis, implementation of the multidisciplinary team approach was the only significant independent prognostic factor for neuroblastoma patients. In further subgroup analyses, the multidisciplinary team approach improved EFS, but not OS, in patients with stage 4 disease, those in the high-risk group, and those with non-MYCN amplified tumors. These data indicate a multidisciplinary team care approach improved survival outcomes in high-risk neuroblastoma patients. However, further investigation will be required to evaluate the long-term effects of this approach over longer follow-up periods.


Cholinergic regulation of protein phosphorylation in bovine adrenal chromaffin cells.
Chromaffin cells were isolated from bovine adrenal medullae and maintained in primary culture. After prelabeling with 32PO4, exposure of the chromaffin cells to acetylcholine increased the phosphorylation of a Mr approximately equal to 100,000 protein and a Mr approximately equal to 60,000 protein (tyrosine hydroxylase), visualized after separation of total cellular proteins in naDodSO4/polyacrylamide gels. Immunoprecipitation with antibodies to three known phosphoproteins ("100-kDa," "87-kDa," and protein III) revealed an acetylcholine-dependent phosphorylation of these proteins. These three proteins were also shown to be present in bovine adrenal chromaffin cells by immunolabeling techniques. "100-kDa" is a Mr approximately equal to 100,000 protein selectively phosphorylated by calcium/calmodulin-dependent protein kinase III, "87-kDa" is a Mr approximately equal to 87,000 protein selectively phosphorylated by protein kinase C, and protein III is a phosphoprotein doublet of Mr approximately equal to 74,000 (IIIa) and Mr approximately equal to 55,000 (IIIb) phosphorylated by cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase I. Furthermore, 100-kDa was shown to be identical to the Mr approximately equal to 100,000 protein whose phosphorylation was increased by acetylcholine treatment. The acetylcholine-dependent increase in phosphorylation of tyrosine hydroxylase, 100-kDa, 87-kDa, and protein III required extracellular calcium and was mimicked by nicotine, veratridine, elevated K+, and calcium ionophore A23187, but not by muscarine. In addition, forskolin increased the phosphorylation of tyrosine hydroxylase, 100-kDa, and protein III, but not that of 87-kDa. Phorbol 12,13-dibutyrate increased the phosphorylation of tyrosine hydroxylase, 87-kDa, and protein III, but not that of 100-kDa. The data demonstrate that cholinergic activation of chromaffin cells increases the phosphorylation of several proteins and that several protein kinase systems may be involved in these effects.


Relationships between components of metabolic syndrome and coronary intravascular ultrasound atherosclerosis measures in women without obstructive coronary artery disease: the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation Study.
In women, metabolic syndrome (MetS) is associated with higher risk of ischemic heart disease-related adverse outcomes versus individual components. We examined the relationship of MetS to subclinical coronary atherosclerosis. Women (n = 100) undergoing coronary angiography for suspected ischemia but without obstructive coronary artery disease (CAD) underwent intravascular ultrasound (IVUS) of a segment of the left coronary artery. A core lab, masked to other findings, assessed IVUS measures and normalized volume measures to pull-back length. MetS [defined using ATPIII criteria (fasting glucose ≥ 100 mg/dl per revised NCEP guideline)] and its components were entered into multiple regression models to assess associations with IVUS measures. Detailed IVUS measurements were available in 87 women. Mean age was 54 ± 10 years, 36% had MetS, and 78% had atheroma. Comparing women with MetS versus without MetS, significant differences were observed for seven IVUS atherosclerosis measures, but were not significant after adjusting for the MetS components. Systolic blood pressure and waist circumference components remained independently positively associated with the IVUS measures after adjusting for age, diabetes, CAD family history, dyslipidemia, smoking, and hormone replacement. In women with signs and symptoms of ischemia and no obstructive CAD, MetS is associated with coronary atherosclerosis presence and severity. However, these associations appear largely driven by components of waist circumference and systolic blood pressure versus MetS cluster. This supports the concept that MetS is a convenient clustering of risk factors rather than an independent risk predictor, and emphasizes that the critical factors for coronary atherosclerosis are potentially modifiable.


The effects of glucose dose and dual-task performance on memory for emotional material.
Whilst previous research has shown that glucose administration can boost memory performance, research investigating the effects of glucose on memory for emotional material has produced mixed findings. Whereas some research has shown that glucose impairs memory for emotional material, other research has shown that glucose has no effect on emotional items. The aim of the present research was therefore to provide further investigation of the role of glucose on the recognition of words with emotional valence by exploring effects of dose and dual-task performance, both of which affect glucose facilitation effects. The results replicated past research in showing that glucose administration, regardless of dose or dual-task conditions, did not affect the memorial advantage enjoyed by emotional material. This therefore suggests an independent relationship between blood glucose levels and memory for emotional material.


Determination of pore-lining residues in the hepatitis C virus p7 protein.
The p7 protein from hepatitis C virus is critical for the assembly and secretion of infectious virus, making it an attractive drug target. It is thought to be a viroporin with a demonstrated ion channel activity when reconstituted into planar lipid bilayers. Electron microscopy experiments suggest that p7 oligomers coexist as hexamers and heptamers. Proposed models of p7 oligomers assume the N-terminal helix to be the pore lining helix. Here, we demonstrate, via electrophysiology, that Cu(2+) has an inhibitory effect on the p7 ion channel and that the amino acid responsible for this inhibition is one histidine in each monomer. This information coupled with the p7 sequence data suggests that the N-terminal helix of p7 does indeed form the transmembrane pore and that this histidine is pore-lining. The information will aid in the construction of oligomeric pore-models and the interpretation of electron microscopy data.


Methylene blue for clinical anaphylaxis treatment: a case report.
Nitric oxide has a pathophysiological role in modulating systemic changes associated with anaphylaxis. Nitric oxide synthase inhibitors may exacerbate bronchospasm in anaphylaxis and worsen clinical conditions, with limited roles in anaphylactic shock treatment. The aim here was to report an anaphylaxis case (not anaphylactic shock), reversed by methylene blue (MB), a guanylyl cyclase inhibitor. A 23-year-old female suddenly presented urticaria and pruritus, initially on her face and arms, then over her whole body. Oral antihistamine was administered initially, but without improvement in symptoms and signs until intravenous methylprednisolone 500 mg. Recurrence occurred after two hours, plus vomiting. Associated upper respiratory distress, pulmonary sibilance, laryngeal stridor and facial angioedema (including erythema and lip edema) marked the evolution. At sites with severe pruritus, petechial lesions were observed. The clinical situation worsened, with dyspnea, tachypnea, peroral cyanosis, laryngeal edema with severe expiratory dyspnea and deepening unconsciousness. Conventional treatment was ineffective. Intubation and ventilatory support were then considered, because of severe hypoventilation. But, before doing that, based on our previous experience, 1.5 mg/kg (120 mg) bolus of 4% MB was infused, followed by one hour of continuous infusion of another 120 mg diluted in dextrose 5% in water. Following the initial intravenous MB dose, the clinical situation reversed completely in less than 20 minutes, thereby avoiding tracheal intubation. Although the nitric oxide hypothesis for MB effectiveness discussed here remains unproven, our intention was to share our accumulated cohort experience, which strongly suggests MB is a lifesaving treatment for anaphylactic shock and/or anaphylaxis and other vasoplegic conditions.


Early course of nicotine dependence in adolescent smokers.
The goal was to characterize the early course of nicotine dependence. Data were collected from 1246 sixth-graders in a 4-year (2002-2006) prospective study using 11 individual interviews. Subjects were monitored for 10 symptoms of dependence by using the Hooked on Nicotine Checklist. The bidirectional prospective relationship between the intensity of dependence (number of symptoms) and smoking frequency was examined by using cross-lagged analyses. Of the 370 subjects who had inhaled from a cigarette, 62% smoked at least once per month, 53% experienced dependence symptoms, and 40% experienced escalation to daily smoking. Smoking frequency predicted the number of dependence symptoms at the next interview, and the number of symptoms predicted reciprocally the observed escalation in smoking frequency. Monthly smoking was a strong risk factor for the development of symptoms (adjusted hazard ratio: 9.9 [95% confidence interval: 6.6-14.8]). A strong desire to smoke was the most common presenting symptom, typically followed by the appearance of symptoms of nicotine withdrawal, escalation to daily smoking, and then reports of feeling addicted or difficulty controlling smoking. The appearance of any dependence symptom increased the risk for daily smoking (hazard ratio: 6.81 [95% confidence interval: 4.4-10.5]). Nondaily tobacco use triggers the emergence of nicotine dependence. Early dependence symptoms promote escalation in smoking frequency and, reciprocally, more-frequent smoking accelerates the appearance of additional symptoms of dependence. As this positive feedback progresses, the symptoms of nicotine dependence present in a typical sequence, with some individual variation.


Predictors of functional outcomes in patients with facioscapulohumeral muscular dystrophy.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent muscular dystrophies characterized by considerable variability in severity, rates of progression and functional outcomes. Few studies follow FSHD cohorts long enough to understand predictors of disease progression and functional outcomes, creating gaps in our understanding, which impacts clinical care and the design of clinical trials. Efforts to identify molecularly targeted therapies create a need to better understand disease characteristics with predictive value to help refine clinical trial strategies and understand trial outcomes. Here we analysed a prospective cohort from a large, longitudinally followed registry of patients with FSHD in the USA to determine predictors of outcomes such as need for wheelchair use. This study analysed de-identified data from 578 individuals with confirmed FSHD type 1 enrolled in the United States National Registry for FSHD Patients and Family members. Data were collected from January 2002 to September 2019 and included an average of 9 years (range 0-18) of follow-up surveys. Data were analysed using descriptive epidemiological techniques, and risk of wheelchair use was determined using Cox proportional hazards models. Supervised machine learning analysis was completed using Random Forest modelling and included all 189 unique features collected from registry questionnaires. A separate medications-only model was created that included 359 unique medications reported by participants. Here we show that smaller allele sizes were predictive of earlier age at onset, diagnosis and likelihood of wheelchair use. Additionally, we show that females were more likely overall to progress to wheelchair use and at a faster rate as compared to males, independent of genetics. Use of machine learning models that included all reported clinical features showed that the effect of allele size on progression to wheelchair use is small compared to disease duration, which may be important to consider in trial design. Medical comorbidities and medication use add to the risk for need for wheelchair dependence, raising the possibility for better medical management impacting outcomes in FSHD. The findings in this study will require further validation in additional, larger datasets but could have implications for clinical care, and inclusion criteria for future clinical trials in FSHD.


Gastric duplication cyst.
The aim of this study is to evaluate the diagnostic and therapeutic difficulties of gastric duplication cysts. A 38-year-old female patient presented with dyspepsia and repeated episodes of epigastric pain. She was operated with the diagnosis of pancreatic pseudocyst according to her US and CT scans, and found to have a gastric duplication cyst. A cyst about 80x80 mm, localized on the posterior wall of the corpus of the stomach close to the fundus, was dissected from the surrounding tissues and partially from the gastric wall. The cyst did not have muscle layer on the common wall with the stomach, so the cystic mucosa was stripped away from the gastric muscle layer. The gastric lumen was not entered. Although gastric duplication cysts do not have specific symptoms and signs, CT, MR and endoscopic ultrasonography may help the preoperative diagnosis, but the diagnosis is usually confirmed at laparotomy. Needle aspiration may cause complications. Because of the complications that may occur after needle aspiration and malignant potential of the tissue, the treatment of these cysts is surgical.


Modeling Large Sparse Data for Feature Selection: Hospital Admission Predictions of the Dementia Patients Using Primary Care Electronic Health Records.
A growing elderly population suffering from incurable, chronic conditions such as dementia present a continual strain on medical services due to mental impairment paired with high comorbidity resulting in increased hospitalization risk. The identification of at risk individuals allows for preventative measures to alleviate said strain. Electronic health records provide opportunity for big data analysis to address such applications. Such data however, provides a challenging problem space for traditional statistics and machine learning due to high dimensionality and sparse data elements. This article proposes a novel machine learning methodology: entropy regularization with ensemble deep neural networks (ECNN), which simultaneously provides high predictive performance of hospitalization of patients with dementia whilst enabling an interpretable heuristic analysis of the model architecture, able to identify individual features of importance within a large feature domain space. Experimental results on health records containing 54,647 features were able to identify 10 event indicators within a patient timeline: a collection of diagnostic events, medication prescriptions and procedural events, the highest ranked being essential hypertension. The resulting subset was still able to provide a highly competitive hospitalization prediction (Accuracy: 0.759) as compared to the full feature domain (Accuracy: 0.755) or traditional feature selection techniques (Accuracy: 0.737), a significant reduction in feature size. The discovery and heuristic evidence of correlation provide evidence for further clinical study of said medical events as potential novel indicators. There also remains great potential for adaption of ECNN within other medical big data domains as a data mining tool for novel risk factor identification.


Effects of amphibian phylogeny, climate and human impact on the occurrence of the amphibian-killing chytrid fungus.
Chytridiomycosis, due to the fungus Batrachochytrium dendrobatidis (Bd), has been associated with the alarming decline and extinction crisis of amphibians worldwide. Because conservation programs are implemented locally, it is essential to understand how the complex interactions among host species, climate and human activities contribute to Bd occurrence at regional scales. Using weighted phylogenetic regressions and model selection, we investigated geographic patterns of Bd occurrence along a latitudinal gradient of 1500 km within a biodiversity hot spot in Chile (1845 individuals sampled from 253 sites and representing 24 species), and its association with climatic, socio-demographic and economic variables. Analyses show that Bd prevalence decreases with latitude although it has increased by almost 10% between 2008 and 2013, possibly reflecting an ongoing spread of Bd following the introduction of Xenopus laevis. Occurrence of Bd was higher in regions with high gross domestic product (particularly near developed centers) and with a high variability in rainfall regimes, whereas models including other bioclimatic or geographic variables, including temperature, exhibited substantially lower fit and virtually no support based on Akaike weights. In addition, Bd prevalence exhibited a strong phylogenetic signal, with five species having high numbers of infected individuals and higher prevalence than the average of 13.3% across all species. Taken together, our results highlight that Bd in Chile might still be spreading south, facilitated by a subset of species that seem to play an important epidemiological role maintaining this pathogen in the communities, in combination with climatic and human factors affecting the availability and quality of amphibian breeding sites. This information may be employed to design conservation strategies and mitigate the impacts of Bd in the biodiversity hot spot of southern Chile, and similar studies may prove useful to disentangle the role of different factors contributing to the emergence and spread of this catastrophic disease.


The real face of HIF1α in the tumor process.
It is well known that the hypoxia-inducible factor 1 α (HIF1α) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1α is detectable even under normoxic conditions, if the metabolism is altered, e.g., high proliferation index. Importantly, both hypoxic metabolism and the Warburg effect have in common a decrease of the intracellular pH value. In our interpretation, HIF1α is not directly accumulated by hypoxia, but by a process which occurs always under hypoxic conditions, a decrease of the intracellular pH value because of metabolic imbalances. We assume that HIF1α is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1α has its major role in activating genes to eliminate toxic metabolic waste products (e.g., NH3/NH4+) generated by the tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or the Warburg effect. For that reason, HIF1α appears as a potential target for tumor therapy to disturb the pH balance and to inhibit the elimination of toxic metabolic waste products in the tumor cells.


Isolation of recombinant viruses between cauliflower mosaic virus and a viral gene in transgenic plants under conditions of moderate selection pressure.
We demonstrate that recombinant viruses formed between a wild-type virus and a viral transgene can be isolated from transgenic plants under conditions of moderate to weak selection pressure. We inoculated cauliflower mosaic virus (CaMV) strain W260 to transgenic Nicotiana bigelovii plants that expressed a copy of CaMV gene VI derived from CaMV strain D4, a gene that determines systemic infection of solanaceous species, including N. bigelovii. Because W260 infects nontransformed N. bigelovii systemically, a recombinant virus formed between W260 and the D4 transgene would be expected to have little selective advantage over the wild-type W260 virus W260 was inoculated to approximately 100 plants each of nontransformed and transgenic N. bigelovii and it systemically infected nearly all of the plants. An analysis of viral DNA recovered from 23 transgenic plants infected with W260 revealed that 20 infections resulted from the systemic movement of the wild-type W260 virus, while a recombinant between W260 and the D4 transgene was detected in three of the infections. To determine the percentage of recovery of recombinant viruses under strong selection pressure, we inoculated approximately 100 nontransformed and 100 D4 gene VI transgenic plants with CaMV strain CM1841, a virus that is unable to infect nontransformed N. bigelovii. CM1841 infected 36% of the transgenic plants systemically, but none of the nontransformed controls. An analysis of 24 infected plants showed that a recombination event occurred in every plant, demonstrating that under strong selection conditions, the recovery of CaMV recombinants from transgenic plants can be very high.


Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series.
This is a series of clinical case reports demonstrating that a combination of percutaneously injected autologous adipose-tissue-derived stem cells, hyaluronic acid, platelet rich plasma and calcium chloride may be able to regenerate bones in human osteonecrosis, and with addition of a very low dose of dexamethasone, cartilage in human knee osteoarthritis. Stem cells were obtained from adipose tissue of abdominal origin by digesting lipoaspirate tissue with collagenase. These stem cells, along with hyaluronic acid, platelet rich plasma and calcium chloride, were injected into the right hip of a 29-year-old Korean woman and a 47-year-old Korean man. They both had a history of right hip osteonecrosis of the femoral head. For cartilage regeneration, a 70-year-old Korean woman and a 79-year-old Korean woman, both with a long history of knee pain due to osteoarthritis, were injected with stem cells along with hyaluronic acid, platelet rich plasma, calcium chloride and a nanogram dose of dexamethasone. Pre-treatment and post-treatment MRI scans, physical therapy, and pain score data were then analyzed. The MRI data for all the patients in this series showed significant positive changes. Probable bone formation was clear in the patients with osteonecrosis, and cartilage regeneration in the patients with osteoarthritis. Along with MRI evidence, the measured physical therapy outcomes, subjective pain, and functional status all improved. Autologous mesenchymal stem cell injection, in conjunction with hyaluronic acid, platelet rich plasma and calcium chloride, is a promising minimally invasive therapy for osteonecrosis of femoral head and, with low-dose dexamethasone, for osteoarthritis of human knees.


Bulk phase resource ratio alters carbon steel corrosion rates and endogenously produced extracellular electron transfer mediators in a sulfate-reducing biofilm.
Desulfovibrio alaskensis G20 biofilms were cultivated on 316 steel, 1018 steel, or borosilicate glass under steady-state conditions in electron-acceptor limiting (EAL) and electron-donor limiting (EDL) conditions with lactate and sulfate in a defined medium. Increased corrosion was observed on 1018 steel under EDL conditions compared to 316 steel, and biofilms on 1018 carbon steel under the EDL condition had at least twofold higher corrosion rates compared to the EAL condition. Protecting the 1018 metal coupon from biofilm colonization significantly reduced corrosion, suggesting that the corrosion mechanism was enhanced through attachment between the material and the biofilm. Metabolomic mass spectrometry analyses demonstrated an increase in a flavin-like molecule under the 1018 EDL condition and sulfonates under the 1018 EAL condition. These data indicate the importance of S-cycling under the EAL condition, and that the EDL is associated with increased biocorrosion via indirect extracellular electron transfer mediated by endogenously produced flavin-like molecules.


Systematic review and meta-analysis: association between water and sanitation environment and maternal mortality.
To assess whether the lack of water or the lack of sanitation facilities in either the home or in health facilities is associated with an increased risk of maternal mortality and to quantify the effect sizes. Systematic review of published literature in Medline, Embase, Popline and Africa Wide EBSCO 1980. Fourteen articles were found. Four of five ecological studies that considered sanitation found that poor sanitation was associated with higher maternal mortality. Meta-analysis of adjusted estimates in individual-level studies indicated that women in households with poor sanitation had 3.07 (95% CI 1.72-5.49) higher odds of maternal mortality. Four of six ecological studies assessing water environment found that poor water environment was associated with higher maternal mortality. The only individual-level study looking at the adjusted effect of water showed a significant association with maternal mortality (OR = 1.50, 95% CI 1.10-2.10). Two ecological and one facility-based study found an association between a combined measure of water and sanitation environment and maternal mortality. There is evidence of association between sanitation and maternal mortality and between water and maternal mortality. Both associations are of substantial magnitude and are maintained after adjusting for confounders. However, these conclusions are based on a very small number of studies, few of which set out to examine sanitation or water as risk factors, and only some of which adjusted for potential confounders. Nevertheless, there are plausible pathways through which such associations may operate.


Learning to use working memory: a reinforcement learning gating model of rule acquisition in rats.
Learning to form appropriate, task-relevant working memory representations is a complex process central to cognition. Gating models frame working memory as a collection of past observations and use reinforcement learning (RL) to solve the problem of when to update these observations. Investigation of how gating models relate to brain and behavior remains, however, at an early stage. The current study sought to explore the ability of simple RL gating models to replicate rule learning behavior in rats. Rats were trained in a maze-based spatial learning task that required animals to make trial-by-trial choices contingent upon their previous experience. Using an abstract version of this task, we tested the ability of two gating algorithms, one based on the Actor-Critic and the other on the State-Action-Reward-State-Action (SARSA) algorithm, to generate behavior consistent with the rats'. Both models produced rule-acquisition behavior consistent with the experimental data, though only the SARSA gating model mirrored faster learning following rule reversal. We also found that both gating models learned multiple strategies in solving the initial task, a property which highlights the multi-agent nature of such models and which is of importance in considering the neural basis of individual differences in behavior.


Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial.
We tested whether chronic supplementation with resveratrol (a phytoestrogen) could improve cerebrovascular function, cognition and mood in post-menopausal women. Eighty post-menopausal women aged 45-85 years were randomised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance, cerebral blood flow velocity and pulsatility index (a measure of arterial stiffness) in the middle cerebral artery (using transcranial Doppler ultrasound), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia were assessed. Mood questionnaires were also administered. Compared to placebo, resveratrol elicited 17% increases in CVR to both hypercapnic (p = 0.010) and cognitive stimuli (p = 0.002). Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020), which correlated with the increase in CVR (r = 0.327; p = 0.048). Mood tended to improve in multiple measures, although not significantly. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.


First report of an exophilic Anopheles arabiensis population in Bissau City, Guinea-Bissau: recent introduction or sampling bias?
The malaria vector Anopheles arabiensis exhibits greater behavioural and ecological plasticity than the other major vectors of the Anopheles gambiae complex, which presents challenges for major control methods. This study reports for the first time the presence of An. arabiensis in Antula, a suburb of Bissau city, the capital of Guinea Bissau, where high levels of hybridization between Anopheles coluzzii and An. gambiae have been reported. Given that previous surveys in the area, based on indoor collections, did not sample An. arabiensis, the possibility of a recently introduced exophilic population was investigated. Larval and adult mosquito collections were carried out in Antula at the end of the rainy season of 2010. Anopheles gambiae species composition, determined by rDNA-IGS and SINE200X6.1 markers, was compared with four previously collected samples dating back to 1993. Analysis of ten microsatellites was used to estimate levels of genetic diversity, relatedness and to investigate demographic stability. Anopheles arabiensis comprised 54.0% of larvae and 25.6% of adults collected in 2010, but was absent in all previous collections, a highly unlikely observation by chance if the population was stable. This species had the lowest levels of genetic diversity, highest relatedness and, along with An. gambiae, exhibited evidence of a recent population expansion. Results point to the presence of a previously undetected outdoor population of An. arabiensis in Antula, which appears to have expanded recently, highlighting the importance of complementing indoor-based mosquito collections with sampling methods targeting outdoor adults and immature stages for a more complete assessment of mosquito biodiversity. A change in temporal dynamics in the species complex composition was also detected. Coupled with previous evidence of asymmetric introgression from An. coluzzii to An. gambiae, this suggests that the study area may be subject to ecological changes with a potential impact on both the genetics of these species and on malaria transmission.


Statin Therapy Is Associated with Reduced Risk of Peptic Ulcer Disease in the Taiwanese Population.
Although statin use may affect the severity of chronic gastritis and gastric cancer, no data exists about the relationship between statin therapy and risk of peptic ulcer disease (PUD) in patients. We investigated the effect of statin use and the incidence of PUD from the Taiwan National Health Insurance Research Database (NHIRD). A total of 35,194 patients records for medical claims were enrolled. We performed a population-based case-control analysis to compare the incidence of PUD in patients who were prescribed statins and that in patients who were not. In the univariate logistic analysis, we found that statin was not significant risk of PUD. However, a multivariate model indicates that satin use was significantly associated with a reduced risk of PUD (adjusted odds ratio [aOR] = 0.87, 95% CI = 0.82-0.93, P < 0.001). The cumulative defined daily dose (DDD) was analyzed. Patients who prescribed fluvastatin ≥280 DDD, atorvastatin ≥200 DDD, and pravastatin ≥130 DDD dramatically decreased risk for PUD (aOR = 0.58, 0.67, and 0.71; 95% CI = 0.46-0.74, 0.57-0.78, and 0.56-0.91, respectively). Our results showed that statin therapy reduced the risk of PUD and this was associated with the high cumulative DDD of prescribed statins. This study reveals that active use of statins to be associated with decreased risk for PUD.


Implementing prevention policies for mother-to-child transmission of HIV in rural Malawi, South Africa and United Republic of Tanzania, 2013-2016.
To assess adoption of World Health Organization (WHO) guidance into national policies for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) and to monitor implementation of guidelines at facility level in rural Malawi, South Africa and the United Republic of Tanzania. We summarized national PMTCT policies and WHO guidance for 15 indicators across the cascades of maternal and infant care over 2013-2016. Two survey rounds were conducted (2013-2015 and 2015-2016) in 46 health facilities serving five health and demographic surveillance system populations. We administered structured questionnaires to facility managers to describe service delivery. We report the proportions of facilities implementing each indicator and the frequency and durations of stock-outs of supplies, by site and survey round. In all countries, national policies influencing the maternal and infant PMTCT cascade of care aligned with WHO guidelines by 2016; most inter-country policy variations concerned linkage to routine HIV care. The proportion of facilities delivering post-test counselling, same-day antiretroviral therapy (ART) initiation, antenatal care and ART provision in the same building, and Option B+ increased or remained at 100% in all sites. Progress in implementing policies on infant diagnosis and treatment varied across sites. Stock-outs of HIV test kits or antiretroviral drugs in the past year declined overall, but were reported by at least one facility per site in both rounds. Progress has been made in implementing PMTCT policy in these settings. However, persistent gaps across the infant cascade of care and supply-chain challenges, risk undermining infant HIV elimination goals.


Mitochondria-targeted platinum(ii) complexes: dual inhibitory activities on tumor cell proliferation and migration/invasion via intracellular trafficking of β-catenin.
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis. Interestingly, PIP-platin can promote cell adhesion within several hours and the cells became hard to dislodge from the culture plate. A wound healing assay, transwell migration/invasion assay and 3D spheroid migration assay all demonstrated that PIP-platin can inhibit cell migration/invasion. To illustrate the associated mechanisms, we investigated the intracellular trafficking of β-catenin, a central protein in the regulation of cell adhesion, and gene transcription for cell proliferation. Upon treatment with PIP-platin, this protein can translocate onto the plasma membrane for increased cell adhesion. In addition, PIP-platin was demonstrated to efficiently inhibit Wnt signaling by blocking the translocation of β-catenin into the nuclei, thereby preventing cell proliferation. We demonstrate that, accordingly, PIP-platin has remarkable potential for intracellular delivery in mitochondria and has inhibitory effects on cancer cell proliferation and migration/invasion through β-catenin, and may therefore be exploited as a dual-functional antitumor drug candidate in cancer treatment.


Exploring Dry-Film FTIR Spectroscopy to Characterize Milk Composition and Subclinical Ketosis throughout a Cow's Lactation.
The use of technologies for measurements of health parameters of individual cows may ensure early detection of diseases and maximization of individual cow and herd potential. In the present study, dry-film Fourier transform infrared spectroscopy (FTIR) was evaluated for the purpose of detecting and quantifying milk components during cows' lactation. This was done in order to investigate if these systematic changes can be used to identify cows experiencing subclinical ketosis. The data included 2329 milk samples from 61 Norwegian Red dairy cows collected during the first 100 days in milk (DIM). The resulting FTIR spectra were used for explorative analyses of the milk composition. Principal component analysis (PCA) was used to search for systematic changes in the milk during the lactation. Partial least squares regression (PLSR) was used to predict the fatty acid (FA) composition of all milk samples and the models obtained were used to evaluate systematic changes in the predicted FA composition during the lactation. The results reveal that systematic changes related to both gross milk composition and fatty acid features can be seen throughout lactation. Differences in the predicted FA composition between cows with subclinical ketosis and normal cows, in particular C14:0 and C18:1cis9, showed that dietary energy deficits may be detected by deviations in distinct fatty acid features.


Hyperuricemia: An Early Marker for Severity of Illness in Sepsis.
Background. Uric acid can acutely activate various inflammatory transcription factors. Since high levels of oxyradicals and lower antioxidant levels in septic patients are believed to result in multiorgan failure, uric acid levels could be used as a marker of oxidative stress and poor prognosis in patients with sepsis. Design. We conducted a prospective cohort study on Medical Intensive Care Unit (MICU) patients and hypothesized that elevated uric acid in patients with sepsis is predictive of greater morbidity. The primary end point was the correlation between hyperuricemia and the morbidity rate. Secondary end points were Acute Kidney Injury (AKI), mortality, Acute Respiratory Distress Syndrome (ARDS), and duration of stay. Results. We enrolled 144 patients. 54 (37.5%) had the primary end point of hyperuricemia. The overall morbidity rate was 85.2%. The probability of having hyperuricemia along with AKI was 68.5% and without AKI was 31.5%. Meanwhile the probability of having a uric acid value <7 mg/dL along with AKI was 18.9% and without AKI was 81.1% (p value < 0.0001). Conclusion. We report that elevated uric acid levels on arrival to the MICU in patients with sepsis are associated with poor prognosis. These patients are at an increased risk for AKI and ARDS.


Experience with the high occipital transcortical approach in the treatment of intraventricular hemorrhage. Report of two cases.
Two patients with intraventricular hemorrhage (IVH) were treated by direct removal of their intraventricular hematomas via a high occipital transcortical approach with successful results. This approach lies between the parietooccipital transcortical approach and the occipital transcortical approach. The patients were a 90-year-old woman with idiopathic IVH and a 60-year-old man with hemorrhage caused by bleeding in the thalamus. In both cases, the hematoma was tightly packed in the lateral ventricle. In the former case, the inferior horn of the lateral ventricle was extremely swollen, and the patient was at risk for development of uncal herniation. With the goals of complete elimination of the hematoma in the inferior horn and identification of the source of bleeding, a high occipital transcortical approach was applied, and the hematoma was removed under direct vision. With the patient in the lateral position, a minor craniotomy of approximately 3 cm was performed around the puncture site of the posterior horn (8 cm craniad from the inion and 3 cm lateral from the midline). A 1-cm cortical incision was made and the posterior horn was reached. First, the portion of hematoma at this site was removed, and then the remainder was completely removed from the interior horn and corpus. Using this method, the entire region of the lateral ventricle, including the inferior horn, corpus, and posterior horn, can be covered in a single operative field, and it is also possible to have sufficient working space for the operation.


Proteoglycans of the intervertebral disc. Homology of structure with laryngeal proteoglycans.
The structure of the proteoglycans from normal pig nucleus pulposus and relatively normal human annulus fibrosus and nucleus pulposus was investigated in detail and the results were compared with the current structural model of proteoglycans of hyaline cartilage. Like proteoglycans of cartilage, those of intervertebral disc contain keratan sulphate and chondroitin sulphate attached to a protein core; they are able to aggregate to hyaluronic acid; the protein core likewise has three regions, one lacking glycosaminoglycans, another rich in keratan sulphate and a third region rich in chondroitin sulphate. However, disc proteoglycans contain more keratan sulphate and protein and less chondroitin sulphate and are also considerably smaller than cartilage proteoglycans. In proteoglycans of human discs, these differences appeared to be due principally to a shorter region of the core protein bearing the chondroitin sulphate chains, whereas in proteoglycans of pig discs their smaller size and relatively low uronic acid content were due to shorter chondroitin sulphate chains. There were subtle differences between proteoglycans from the nucleus and annulus of human discs. In the latter a higher proportion of proteoglycans was capable of binding to hyaluronate.


Marijuana sources in a medical marijuana environment: dynamics in access and use among a cohort of young adults in Los Angeles, California.
While a range of sources exist for marijuana users to acquire marijuana for medical or personal use, prior research on marijuana sources primarily focused on single sources. In this analysis, we longitudinally examined characteristics of multiple sources selected by marijuana users, motivations to use sources, and how a blend of marijuana sources accommodated users' needs. Young adult marijuana users (n=60) in Los Angeles, CA, where marijuana has been legal for medical use since 1996, completed two annual qualitative interviews on marijuana use practices and sources between 2014 and 2016. Approximately two-thirds were medical marijuana patients and one-third were non-patient users. Participants reported acquiring marijuana from the following primary sources across two interviews: dispensaries and delivery services, private sellers in the illicit market, friends and family, and marijuana events/conferences. While patients with legal medical access to marijuana typically purchased marijuana from dispensaries or delivery services, they often supplemented from other illicit sources. Non-patients often accessed marijuana through dispensary diversion but also other sources. As patients became non-patients and vice versa during the study period, source type changed too. Broad access to marijuana via legal and illicit sources in this sample is indicative of societal trends towards normalization of marijuana use.


Hypogonadism and infertility in testicular cancer survivors.
Testicular cancer is the most common cancer in men in their 20s and 30s, and has been considered a model of a curable neoplasm. The longer life expectancy of testicular cancer survivors makes minimizing the long-term health issues related to hypogonadism particularly important, and because testicular cancer affects men mostly in their reproductive years, infertility can also be a major concern. Hypogonadism, infertility, and testicular cancer have been associated with one another. These associations suggest the existence of common etiologic factors, including improper testicular development during fetal life. The effect of cancer treatment on testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and on fertility and overall paternity rates among testicular cancer survivors, are potentially significant issues. As the biologic mechanisms underlying hypogonadism, infertility, and testicular cancer become clearer, more research is needed to provide clinicians with evidence-based guidelines for the management of testicular cancer survivors.


Modulation of KdpD phosphatase implicated in the physiological expression of the kdp ATPase of Escherichia coli.
The KdpD sensor kinase and the KdpE response regulator control the expression of the kdpFABC operon, encoding the KdpFABC high-affinity K+ transport system of Escherichia coli. Low turgor pressure has been postulated to be the environmental stimulus to express KdpFABC. KdpD has autokinase, phosphotransferase and, like many sensor kinases, response regulator (phospho-KdpE) specific phosphatase activity. To determine which of these activities are altered in response to the environmental stimulus, we isolated and analysed six kdpD mutants that cause constitutive expression of KdpFABC. In three of the mutants, phosphatase activity was undetectable and, in two, phosphatase was reduced. Kinase activity was unaffected in four of the mutants, but elevated in one. In one mutant, a pseudorevertant of a kdpD null mutation, kinase and phosphatase were both reduced to 20% of the wild-type level. These findings suggest that initiation of signal transduction by KdpD is mediated by the inhibition of the phospho-KdpE-specific phosphatase activity of KdpD, leading to an accumulation of phospho-KdpE, which in turn activates the expression of the KdpFABC system. The data also suggest that levels of activity in vitro may differ from what occurs in vivo, because in vitro conditions cannot replicate those in vivo.


Comparison of statistical methods for estimating genetic admixture in a lung cancer study of African Americans and Latinos.
A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998-2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors.


High division of the axillary artery. A rare case of superficial ulnar artery.
A case is presented here in which the axillary artery divided into two branches, the lateral branch being situated more deeply with respect to the medial branch. The superficial branch gave rise to only thin muscular branches in the arm and coursed along the ulnar artery in the forearm but did not provide the branches which should arise from this artery. On the other hand, the deeply coursing artery provided the branches of the brachial artery in the arm and from the cubital fossa downwards it provided the branches which normally arise from the ulnar artery.


The role of physician and nurse attitudes in the health care of injecting drug users.
In 2005, 60 health care workers were recruited through services that attract injecting drug users (IDUs) and asked to complete attitude measures regarding IDU clients. Mediation analyses indicated that conservative health care workers displayed more negative attitudes toward their IDU clients because they believe that injecting drug use is within the control of the IDU. Negative attitudes toward IDU clients, in turn, were associated with worry about IDU clients' behavior in the clinic and with beliefs that IDU clients should disclose their hepatitis C status to their health care worker. Perceptions of controllability of drug use were also associated with the belief that IDU clients' ailments were caused by their IDU status. The study's limitations are noted.


An epidemiologic study to determine the prevalence of the HLA-B*5701 allele among HIV-positive patients in Europe.
HLA-B*5701 is a major histocompatibility complex class I allele associated with an immunologically-mediated hypersensitivity reaction to abacavir. The objectives of this study were to evaluate HLA-B*5701 prevalence among European, HIV-1-infected patients and to compare the local and central laboratory screening results. Data were combined from six multicentre, prospective studies involving 10 European countries in which HIV-1-infected patients (irrespective of treatment experience or previous HLA-B*5701 screening), >or=18 years of age, were evaluated for HLA-B*5701 carriage, determined by the central and local laboratory methods. A total of 9720 patients from 272 centres were included in the analysis. The overall estimate of HLA-B*5701 prevalence in Europe was 4.98%, with country-specific estimates ranging from 1.53 to 7.75%. HLA-B*5701 prevalence was highest in the self-reported white population (6.49%) and lowest in the black population (0.39%). Local laboratory results had a high specificity (99.9%) and sensitivity (99.2%) when compared with the central laboratory results. This study supports data from previous studies regarding the prevalence of HLA-B*5701 in the HIV population and the variation of HLA-B*5701 prevalence between different racial groups. The high specificity and sensitivity of local laboratory results, suggests that clinicians can be confident in using local laboratories for pretreatment HLA-B*5701 screening. However, it is essential that local laboratories participate in HLA-B*5701-specific quality assurance programs to maintain 100% sensitivity. In HIV-infected patients, pretreatment HLA-B*5701 screening may allow more informed decisions regarding abacavir use and has the potential to significantly reduce the frequency of abacavir-related hypersensitivity reactions and costs associated with managing these reactions.


Value-Added Compound Recovery from Invasive Forest for Biofunctional Applications: Eucalyptus Species as a Case Study.
From ancient times, the medicinal properties of the different Eucalyptus species are well known. In fact, plants from this family have been used in folk medicine as antiseptics, and to treat different ailments of the upper respiratory tract such as sinus congestion, common cold, or influenza. Moreover, other biological activities were described for Eucalyptus species such as antioxidant and antimicrobial properties. In the last few decades, numerous investigations revealed that the compounds responsible for these properties are secondary metabolites that belonging to the group of phenolic compounds and are present in different parts of the plants such as leaves, bark, wood, fruits, and stumps. The increasing demand for natural compounds that can substitute synthetic antioxidants and the increase in resistance to traditional antibiotics have boosted the intense search for renewable natural sources containing substances with such bioactivities, as well as greener extraction technologies and avant-garde analytical methods for the identification of the target molecules. The literature data used in this paper were collected via Scopus (2001-2020) using the following search terms: Eucalyptus, extraction methods, phenolic compounds, and biological activities. This review collects the main studies related to the recovery of value-added compounds from different Eucalyptus species, as well as their biofunctional applications.


Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway.
The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pathomechanisms of neurodegenerative disease. Here we show that continued 26S proteasome dysfunction in mouse brain cortical neurons causes paranuclear accumulation of fragmented dysfunctional mitochondria, associated with earlier recruitment of Parkin and lysine 48-linked ubiquitination of mitochondrial outer membrane (MOM) proteins, including Mitofusin-2. Early events also include phosphorylation of p62/SQSTM1 (p62) and increased optineurin, as well as autophagosomal LC3B and removal of some mitochondria, supporting the induction of selective autophagy. Inhibition of the degradation of ubiquitinated MOM proteins with continued 26S proteasome dysfunction at later stages may impede efficient mitophagy. However, continued 26S proteasome dysfunction also decreases the levels of essential autophagy proteins ATG9 and LC3B, which is characterised by decreases in their gene expression, ultimately leading to impaired autophagy. Intriguingly, serine 351 phosphorylation of p62 did not enhance its binding to Keap1 or stabilise the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor in this neuronal context. Nrf2 protein levels were markedly decreased despite transcriptional activation of the Nrf2 gene. Our study reveals novel insights into the interplay between the UPS and autophagy in neurons and is imperative to understanding neurodegenerative disease where long-term proteasome inhibition has been implicated.


The globin gene repertoire of lampreys: convergent evolution of hemoglobin and myoglobin in jawed and jawless vertebrates.
Agnathans (jawless vertebrates) occupy a key phylogenetic position for illuminating the evolution of vertebrate anatomy and physiology. Evaluation of the agnathan globin gene repertoire can thus aid efforts to reconstruct the origin and evolution of the globin genes of vertebrates, a superfamily that includes the well-known model proteins hemoglobin and myoglobin. Here, we report a comprehensive analysis of the genome of the sea lamprey (Petromyzon marinus) which revealed 23 intact globin genes and two hemoglobin pseudogenes. Analyses of the genome of the Arctic lamprey (Lethenteron camtschaticum) identified 18 full length and five partial globin gene sequences. The majority of the globin genes in both lamprey species correspond to the known agnathan hemoglobins. Both genomes harbor two copies of globin X, an ancient globin gene that has a broad phylogenetic distribution in the animal kingdom. Surprisingly, we found no evidence for an ortholog of neuroglobin in the lamprey genomes. Expression and phylogenetic analyses identified an ortholog of cytoglobin in the lampreys; in fact, our results indicate that cytoglobin is the only orthologous vertebrate-specific globin that has been retained in both gnathostomes and agnathans. Notably, we also found two globins that are highly expressed in the heart of P. marinus, thus representing functional myoglobins. Both genes have orthologs in L. camtschaticum. Phylogenetic analyses indicate that these heart-expressed globins are not orthologous to the myoglobins of jawed vertebrates (Gnathostomata), but originated independently within the agnathans. The agnathan myoglobin and hemoglobin proteins form a monophyletic group to the exclusion of functionally analogous myoglobins and hemoglobins of gnathostomes, indicating that specialized respiratory proteins for O2 transport in the blood and O2 storage in the striated muscles evolved independently in both lineages. This dual convergence of O2-transport and O2-storage proteins in agnathans and gnathostomes involved the convergent co-option of different precursor proteins in the ancestral globin repertoire of vertebrates.


Fluticasone furoate: intranasal use in allergic rhinitis.
Fluticasone furoate nasal spray is a new topical intranasal corticosteroid with enhanced affinity for the glucocorticoid receptor and low systemic exposure, which was recently approved in the US for the treatment of seasonal or perennial allergic rhinitis in adults and in children aged >or=2 years. Fluticasone furoate nasal spray employs a novel delivery device with a unique side-actuated design, a short nozzle and a new trigger mechanism designed for ease of use. In well controlled clinical trials, intranasal fluticasone furoate 110microg once daily for 2 weeks in adults and adolescents with seasonal allergic rhinitis reduced nasal and ocular symptoms, and improved health-related quality of life to a significantly greater extent than placebo. Similarly, treatment with intranasal fluticasone furoate 110microg once daily for 4-6 weeks in adults and adolescents with perennial allergic rhinitis was superior to placebo in reducing nasal symptoms and with respect to overall response to therapy. In children aged 6-11 years, fluticasone furoate nasal spray was shown to be effective in reducing the nasal symptoms of seasonal and perennial allergic rhinitis following treatment for 2 and 4 weeks, respectively. Fluticasone furoate nasal spray was well tolerated in adults, adolescents and children aged 2-11 years, with an overall incidence of adverse events similar to that with placebo.


The Measurement of Local Variation in Shape.
Geometric morphometrics comprises tools for measuring and analyzing shape as captured by an entire set of landmark configurations. Many interesting questions in evolutionary, genetic, and developmental research, however, are only meaningful at a local level, where a focus on "parts" or "traits" takes priority over properties of wholes. To study variational properties of such traits, current approaches partition configurations into subsets of landmarks which are then studied separately. This approach is unable to fully capture both variational and spatial characteristics of these subsets because interpretability of shape differences is context-dependent. Landmarks omitted from a partition usually contain information about that partition's shape. We present an interpolation-based approach that can be used to model shape differences at a local, infinitesimal level as a function of information available globally. This approach belongs in a large family of methods that see shape differences as continuous "fields" spanning an entire structure, for which landmarks serve as reference parameters rather than as data. We show, via analyses of simulated and real data, how interpolation models provide a more accurate representation of regional shapes than partitioned data. A key difference of this interpolation approach from current morphometric practice is that one must assume an explicit interpolation model, which in turn implies a particular kind of behavior of the regions between landmarks. This choice presents novel methodological challenges, but also an opportunity to incorporate and test biomechanical models that have sought to explain tissue-level processes underlying the generation of morphological shape.


Relationship of environmental tobacco smoke to otitis media (OM) in children.
Many, but not all, studies have found a correlation between environmental tobacco smoke (ETS) and acute otitis media (AOM) and other adverse otologic outcomes. Given its high personal and societal costs and the divergent findings of the effect of ETS on middle ear disease, the aim of the current study was to assess the impact and possible determinant factors of ETS on recurrent (two or more) episodes of AOM. The study was performed at Heim Pal Children's Hospital, Ear, Nose and Throat (ENT) Department, Budapest, Hungary. Caregivers of a convenience sample of 412 children attending the ENT outpatient clinic were surveyed via a 22-item questionnaire regarding demographics, socioeconomics, and smoking behaviours of the child's family; as well as care-givers' self report of the number of AOM episodes of the child. Of the 412 participants, 155 (38%) children's parents smoked. In bivariate analysis, two or more episodes of AOM correlated with reported hearing problems, day care enrolment, parental employment and increased age of the child. In multivariate logistic regression, parental smoking more than doubled a child's risk for recurrent AOM while increased maternal employment (e.g. part-time or full-time versus unemployed) boosted risk up to fourfold. Among children whose parents smoked, half-packs of cigarettes smoked per day and day care attendance doubled or nearly tripled, respectively, the risk of recurrent AOM episodes. Childhood exposure to ETS is high among an ENT clinic population of Hungarian children. Such exposure correlates with AOM episodes, ENT operations and conductive hearing loss. Data such as these argue for strict laws smoke-free laws not only in Hungary, but also in Europe and around the world.


In situ light-scattering measurements of morphologically evolving flame-synthesized oxide nanoaggregates.
Nonspherical Al2O3 aggregates produced in a laminar counterflow nonpremixed methane flame were investigated with an in situ laser light-scattering (LLS) technique in combination with a thermophoretic sampling-transmission electron microscope (TS-TEM) method. These flame-synthesized nanoparticles clearly underwent morphological changes following their formation (from precursor trimethylaluminum hydrolysis), mainly as a result of aggregation and sintering processes in the approximately 3.3 x 10(4) K/s heating environment. To characterize this particulate morphological evolution conveniently we made multiangular absolute LLS measurements and interpreted them based on the Rayleigh-Debye-Gans scattering theory for fractal aggregates. Optically determined fractal dimension D(f), mean radius of gyration, aggregate size distribution, and local particle volume fraction phi(p) were found to be consistent with our independent ex situ TS-TEM experiments. D(f) (optically inferred) increased from 1.60 to 1.84 with axial position, confirming the morphological evolution of alumina aggregates owing to finite-rate, spatially resolved high-temperature sintering. An extension of our TS-TEM method was successfully applied, for the first time to our knowledge, to inorganic particles. Phi(p) inferred by means of this ex situ technique generally agreed with that from the in situ LLS technique, supporting our interpretation of both measurements. Moreover, an optically inferred net sintering rate of alumina aggregates approaching the flame was estimated to be consistent with the available TEM data. The LLS methods and results presented here are expected to permit more comprehensive mechanistic analyses of nanoaggregate sintering and coagulation kinetics in such flame environments, ultimately improving the modeling of more-complex (e.g., turbulent, high-pressure) combustion systems involving nanoparticle formation and evolution.


Subjective social status, life course SES, and BMI in young adulthood.
Socioeconomic status (SES) is associated with many aspects of health and well-being, including body mass index (BMI). Most research in this area has focused on objective indicators of SES such as education and income, but recent work suggests that subjective social status (SSS) is also important. This study contributes to a growing body of research on SSS and BMI. Data from Waves I and IV the National Longitudinal Study of Adolescent to Adult Health (Add Health), a study of 14,780 individuals followed from adolescence to young adulthood, were analyzed. Analyses showed that (a) SSS was inversely associated with BMI among young adults, (b) objective SES in both adulthood and early life explained about half of this relationship, (c) SSS appeared to offer a partial explanation for the association between SES (in both adulthood and early life) and BMI, (d) health behaviors, psychological characteristics, self-rated health, and perceived stress explained part of the relationship between SSS and BMI after controlling for SES and other covariates, and (e) SSS had a residual association with BMI that was not accounted for by any of the variables in the full model. This work shows that SSS is important because it (a) has an independent association with BMI net of SES, which suggests that it captures unique aspects of social and economic conditions missed by objective indicators of SES and (b) may help link SES with BMI through perceptions of one's place in the status hierarchy of society. (PsycINFO Database Record


General three-state model with biased population replacement: analytical solution and application to language dynamics.
Empirical evidence shows that the rate of irregular usage of English verbs exhibits discontinuity as a function of their frequency: the most frequent verbs tend to be totally irregular. We aim to qualitatively understand the origin of this feature by studying simple agent-based models of language dynamics, where each agent adopts an inflectional state for a verb and may change it upon interaction with other agents. At the same time, agents are replaced at some rate by new agents adopting the regular form. In models with only two inflectional states (regular and irregular), we observe that either all verbs regularize irrespective of their frequency, or a continuous transition occurs between a low-frequency state, where the lemma becomes fully regular, and a high-frequency one, where both forms coexist. Introducing a third (mixed) state, wherein agents may use either form, we find that a third, qualitatively different behavior may emerge, namely, a discontinuous transition in frequency. We introduce and solve analytically a very general class of three-state models that allows us to fully understand these behaviors in a unified framework. Realistic sets of interaction rules, including the well-known naming game (NG) model, result in a discontinuous transition, in agreement with recent empirical findings. We also point out that the distinction between speaker and hearer in the interaction has no effect on the collective behavior. The results for the general three-state model, although discussed in terms of language dynamics, are widely applicable.


Contrasting patterns of genetic structure in two species of the coral trout Plectropomus (Serranidae) from east and west Australia: introgressive hybridisation or ancestral polymorphisms.
Inter-specific genetic relationships among regional populations of two species of grouper (Plectropomus maculatus and Plectropomus leopardus) were examined using mitochondrial and nuclear markers. mtDNA revealed contrasting regional inter-specific patterns whilst nuclear markers revealed contrasting patterns among markers, irrespective of region. In eastern Australia (EA) the species form a single mtDNA lineage, but the two species are reciprocally monophyletic in Western Australia (WA). This supports previous evidence for hybridisation between these species on the east coast. WA P. leopardus forms a sister relationship with the EA P. leopardus-maculatus clade while WA P. maculatus is more basal and sister to the P. leopardus lineages, indicating mtDNA does not suffer from incomplete lineage sorting for these species. In contrast, one of three nuclear markers (locus 7-90TG) differentiated the species into two reciprocally monophyletic clades, with no evidence of hybridisation or ancestral polymorphism. The remaining two nuclear markers (2-22 and ETS-2) did not separate these two species, while distinguishing other plectropomid species, suggesting incomplete lineage sorting at these nuclear loci. These results together with coalescence analyses suggest that P. leopardus females have hybridised historically with P. maculatus males and that P. maculatus mitochondria were displaced through introgressive hybridisation and fixation in the P. maculatus founder population on the Great Barrier Reef. The contrasting regional patterns of mtDNA structure may be attributed to Quaternary sea-level changes and shelf width differences driving different reef configurations on each coast. These reef configurations have provided opportunities for local scale interaction and reproduction among species on the narrower EA continental shelves, but not on the broader WA continental shelves.


Yellow fever vaccination coverage following massive emergency immunization campaigns in rural Uganda, May 2011: a community cluster survey.
Following an outbreak of yellow fever in northern Uganda in December 2010, Ministry of Health conducted a massive emergency vaccination campaign in January 2011. The reported vaccination coverage in Pader District was 75.9%. Administrative coverage though timely, is affected by incorrect population estimates and over or under reporting of vaccination doses administered. This paper presents the validated yellow fever vaccination coverage following massive emergency immunization campaigns in Pader district. A cross sectional cluster survey was carried out in May 2011 among communities in Pader district and 680 respondents were indentified using the modified World Health Organization (WHO) 40 × 17 cluster survey sampling methodology. Respondents were aged nine months and above. Interviewer administered questionnaires were used to collect data on demographic characteristics, vaccination status and reasons for none vaccination. Vaccination status was assessed using self reports and vaccination card evidence. Our main outcomes were measures of yellow fever vaccination coverage in each age-specific stratum, overall, and disaggregated by age and sex, adjusting for the clustered design and the size of the population in each stratum. Of the 680 survey respondents, 654 (96.1%, 95% CI 94.9 - 97.8) reported being vaccinated during the last campaign but only 353 (51.6%, 95% CI 47.2 - 56.1) had valid yellow fever vaccination cards. Of the 280 children below 5 years, 269 (96.1%, 95% CI 93.7 - 98.7) were vaccinated and nearly all males 299 (96.9%, 95% CI 94.3 - 99.5) were vaccinated. The main reasons for none vaccination were; having travelled out of Pader district during the campaign period (40.0%), lack of transport to immunization posts (28.0%) and, sickness at the time of vaccination (16.0%). Our results show that actual yellow fever vaccination coverage was high and satisfactory in Pader district since it was above the desired minimum threshold coverage of 80% according to World Health Organization. Massive emergency vaccination done following an outbreak of Yellow fever achieved high population coverage in Pader district. Active surveillance is necessary for early detection of yellow fever cases.


Factors contributing to farm-level productivity and household income generation in coastal Bangladesh's rice-based farming systems.
Large changes have taken place in smallholder farming systems in South Asia's coastal areas in recent decades, particularly related to cropping intensity, input availability, climate risks, and off-farm activities. However, few studies have investigated the extent to which these changes have impacted farm-level crop productivity, which is a key driver of food security and poverty in rainfed, low-input, rice-based systems. The objective of this study was to conduct an integrated assessment of variables related to socioeconomic status, farm characteristics, and crop management practices to understand the major factors influencing crop productivity and identify promising leverage points for sustainable development in coastal Bangladesh. Using a panel survey dataset of 32 variables from 502 farm households located within polder (coastal embankment) and outside polder systems during 2005-2015, we employed statistical factor analysis to characterize five independent latent factors named here as Farming Challenges, Economic Status, Crop Management Practices, Asset Endowment, and Farm Characteristics. The factor Farming Challenges explained the most variation among households (31%), with decreases observed over time, specifically households located outside polders. Individual variables contributing to this factor included perceived cyclone severity, household distance to main roads and input-output markets, cropping intensity, and access to extension services. The most important factors for increasing crop productivity on a household and per unit area basis were Asset Endowment and Crop Management Practices, respectively. The former highlights the need for increasing gross cropped area, which can be achieved through greater cropping intensity, while the latter was associated with increased fertilizer, labor, and pesticide input use. Despite the importance of these factors, household poverty trajectory maps showed that changes in off-farm income had played the strongest role in improving livelihoods in this coastal area. This study can help inform development efforts and policies for boosting farm-level crop productivity, specifically through agricultural intensification (higher cropping intensity combined with appropriate and efficient use of inputs) and expanding opportunities for off-farm income as key pathways to bring smallholder households out of poverty.