Neuromorphic Hardware Learns to Learn.
Hyperparameters and learning algorithms for neuromorphic hardware are usually chosen by hand to suit a particular task. In contrast, networks of neurons in the brain were optimized through extensive evolutionary and developmental processes to work well on a range of computing and learning tasks. Occasionally this process has been emulated through genetic algorithms, but these require themselves hand-design of their details and tend to provide a limited range of improvements. We employ instead other powerful gradient-free optimization tools, such as cross-entropy methods and evolutionary strategies, in order to port the function of biological optimization processes to neuromorphic hardware. As an example, we show these optimization algorithms enable neuromorphic agents to learn very efficiently from rewards. In particular, meta-plasticity, i.e., the optimization of the learning rule which they use, substantially enhances reward-based learning capability of the hardware. In addition, we demonstrate for the first time Learning-to-Learn benefits from such hardware, in particular, the capability to extract abstract knowledge from prior learning experiences that speeds up the learning of new but related tasks. Learning-to-Learn is especially suited for accelerated neuromorphic hardware, since it makes it feasible to carry out the required very large number of network computations.


Fabrication of alignment structures for a fiber resonator by use of deep-ultraviolet lithography.
We present a novel method to mount and align an optical-fiber-based resonator on the flat surface of an atom chip with ultrahigh precision. The structures for mounting a pair of fibers, which constitute the fiber resonator, are produced by a spin-coated SU-8 photoresist technique by use of deep-UV lithography. The design and production of the SU-8 structures are discussed. From the measured finesses we calculate the coupling loss of the SU-8 structures acting as a kind of fiber splice to be smaller than 0.013 dB.


Physalis angulata: A New Natural Host of Tomato chlorosis virus in Brazil.
Tomato chlorosis virus (ToCV) and Tomato infectious chlorosis virus (TICV) are the two Solanaceae-infecting Crinivirus species (family Closteroviridae) of worldwide importance. In Brazil, only ToCV has been detected under natural conditions infecting tomato (Solanum lycopersicum), sweet pepper (Capsicum annuum), and potato (S. tuberosum), causing foliar chlorosis (1, 3). However, there are no formal reports of alternative weed hosts of ToCV. During crop surveys in Capão Bonito, São Paulo State, Brazil (May 2011), a high incidence (above 20%) of plants of the weed, cut leaf ground cherry (Physalis angulata L.) growing around and within a tomato (cv. Alambra) field with a high incidence of ToCV, were found displaying interveinal chlorosis on the lower leaves, similar to those induced by magnesium deficiency. The P. angulata plants also had high populations of whiteflies (Bemisia tabaci biotype B). Ten leaf samples were taken from individual symptomatic ground cherry and tomato plants for Crinivirus testing. Total nucleic acids were extracted from 2 g of symptomatic and healthy leaf tissues of both hosts using Whatman CF-11 cellulose (Sigma) as described (4). The purified double stranded RNA samples were used as a template in reverse transcription (RT)-PCR using specific primers targeting the p22 gene region in the genome of ToCV (2). Only the 566-bp ToCV-specific amplicon was detected in all field samples. Sequences of samples from the P. angulata and tomato cDNA amplicons were identical to each other (GenBank Accession No. JX187514) and they showed 99% identity with the ToCV RNA 1 from a tomato isolate from Florida (AY903447). This confirmed the initial hypothesis of Crinivirus infection. Cuttings of symptomatic P. angulata plants were also obtained and kept in a voile cage under greenhouse conditions together with healthy seedlings of P. angulata and the begomovirus-resistant inbred tomato line 'TX-468RG.' Fifty aviruliferous B. tabaci (biotype B) adults were placed in the cage. Similar symptoms were observed 50 days after exposure to whiteflies in both hosts. Transmission to P. angulata and to 'TX-468RG' was also confirmed via sequencing of ToCV-specific amplicon, demonstrating the infectivity of the isolate to both hosts. To our knowledge, this is the first report of P. angulata as a natural host of ToCV in Brazil. This weed is often present in the commercial fields because of its natural tolerance to herbicides currently used in tomato production. The ToCV-infected P. angulata plants might serve as alternative sources of inoculum for the surrounding tomato fields. The environmental persistence of P. angulata combined with its intense whitefly colonization might allow a year-round ToCV exposure for tomato plants under field conditions in this major production area of Brazil where at least 25 million tomato plants are cultivated annually. References: (1) J. C. Barbosa et al. Trop. Plant Pathol. 36: 256, 2011. (2) M. I. Font et al. Plant Dis. 86:696, 2002. (3) D. M. S. Freitas et al. Plant Dis. 96:593, 2012. (4) R. A. Valverde et al. Plant Dis. 74:285, 1990.


Use of cyanoacrylate in the coaptation of edges of surgical wounds.
Cyanoacrylate has been used in several fields of different surgical specialties as an adhesive for closure of gingival flaps and in mucous and cutaneous lacerations. One of its advantages is that it has an excellent immunological response. In view of aesthetic needs, cyanoacrylate has been applied with satisfactory results, when compared with sutures. It presents better coaptation of edges of cutaneous and mucosal lesions, smaller residual scars, and biocompatibility. However, it is limited to areas of little tissue tension. This work attempts to provide a literature review with the aim of revealing the advantages of using tissue adhesives, especially cyanoacrylates, in wound coaptation in comparison with conventional methods.


Are parents doing what they want to do? Congruency between parents' actual and desired participation in the care of their hospitalized child.
Family-centered care is integral to pediatric nursing practice, and includes supporting parents to participate in their hospitalized child's care. Research to date suggests that parents' actual participation in care may differ from their desired participation in care, and that such discrepancies may cause parental distress. Supporting parental participation in a way that facilitates congruency between actual and desired participation may contribute to a satisfying experience for families of hospitalized children. This cross-sectional study measured parents' actual and desired level of participation in care of their hospitalized child and examined the congruency between them. Participants (N = 191), the majority of whom were mothers, provided demographic data and completed two instruments measuring desired and actual participation in care. Study results indicate a significant difference between parents' actual and desired participation (t = -9.382, df = 190, p < 0.0001). The majority of parents expressed a desire to increase their participation. The care activities in which these parents participated are described, including providing comfort, assisting with activities of daily living and advocating for their child. Nurses caring for hospitalized children and their families need to remember that parental preferences for participation will vary, and they need to be prepared to support parents' participation at the level parents choose. Understanding congruency between actual and desired levels of participation can promote awareness of parents' preferences for participation.


Small volume plasma exchange for Guillain-Barré syndrome in resource-limited settings: a phase II safety and feasibility study.
To assess the safety and feasibility of small volume plasma exchange (SVPE) for patients with Guillain-Barré syndrome (GBS). Non-randomised, single-arm, interventional trial. National Institute of Neurosciences and Hospital, Dhaka, Bangladesh. Twenty adult (>18 years) patients with GBS presented within 2 weeks of onset of weakness who were unable to walk unaided for more than 10 m. SVPE involves blood cell sedimentation in a blood bag and removal of supernatant plasma after blood cells are retransfused. This procedure was repeated three to six times a day, for eight consecutive days. Fresh frozen plasma (FFP) and normal saline were used as replacement fluid. Serious adverse events (SAEs) were defined as severe sepsis and deep venous thrombosis related to the central venous catheter (CVC) used during SVPE. SVPE was considered safe if less than 5/20 patients experienced an SAE, and feasible if 8 L plasma could be removed within 8 days in at least 15/20 patients. Median patient age 33 years (IQR 23-46; range 18-55); 13 (65%) were male. Median Medical Research Council (MRC) sum score was 20 (IQR 0-29; range 0-36); three (15%) patients required mechanical ventilation. One patient developed SAE (severe sepsis, possibly related to CVC). The median plasma volume exchanged was 140 mL/kg (range 110-175) and removal of 8 L plasma was possible in 15 (75%) patients. Patients received a median 1 g/kg IgG via FFP although a substantial proportion of IgG was probably removed again by the SVPE sessions. GBS disability score improved by at least one grade in 14 (70%) patients 4 weeks after SVPE started. No patients died. SVPE seems a safe and feasible alternative treatment to standard plasma exchange (PE) or intravenous immunoglobulin (IVIg) for GBS; further studies of clinical efficacy in low-income and middle-income countries are warranted. NCT02780570.


Blackmailing: the keystone in the human mating system.
The human mating system is characterized by bi-parental care and faithful monogamy is highly valued in most cultures. Marriage has evolved as a social institution and punishment for extra pair mating (EPM) or adultery is common. However, similar to other species with bi-parental care, both males and females frequently indulge in EPM in secrecy since it confers certain gender specific genetic benefits. Stability of faithful monogamy is therefore a conundrum. We model human mating system using game theory framework to study the effects of factors that can stabilize or destabilize faithful committed monogamy. Although mate guarding can partly protect the genetic interests, we show that it does not ensure monogamy. Social policing enabled by gossiping is another line of defense against adultery unique to humans. However, social policing has a small but positive cost to an individual and therefore is prone to free riding. We suggest that since exposure of adultery can invite severe punishment, the policing individuals can blackmail opportunistically whenever the circumstances permit. If the maximum probabilistic benefit of blackmailing is greater than the cost of policing, policing becomes a non-altruistic act and stabilizes in the society. We show that this dynamics leads to the coexistence of different strategies in oscillations, with obligate monogamy maintained at a high level. Deletion of blackmailing benefit from the model leads to the complete disappearance of obligate monogamy. Obligate monogamy can be maintained in the population in spite of the advantages of EPM. Blackmailing, which makes policing a non-altruistic act, is crucial for the maintenance of faithful monogamy. Although biparental care, EPM, mate guarding and punishment are shared by many species, gossiping and blackmailing make the human mating system unique.


Reversal of tubal sterilization using laparoscopically placed titanium staples: preliminary experience.
We tested the feasibility of performing outpatient laparoscopic surgery to reverse tubal sterilization using titanium staples to reapproximate the oviducts. A total of 14 women underwent the procedure which involved excision of the tubal eschar, stenting of the severed remnants, and circumferential stapling of the muscularis and serosa. Reapproximation was possible in all cases, with a measured tubal length post-anastomosis of 4.5 +/- 0.5 cm (range 3.0-7.0 cm). The length of operating time was 2.8 +/- 0.2 h (range 2.2-3.8 h), and all patients were discharged the same day. There were no operative complications, and no readmissions were necessary. Within 6 months of surgery there were six pregnancies including one spontaneous abortion and five ongoing pregnancies. Of those not conceiving within 8 months, seven (100%) demonstrated tubal patency on a follow-up hysterosalpingogram. We conclude the laparoscopic approach to tubal sterilization reversal is a viable alternative to open abdominal microsurgical approaches. Although preliminary, laparoscopic surgery promises to be cost effective, as it can be performed on an outpatient basis, may reduce operative time and minimizes the recuperative period of patients.


Genomics, proteomics and bioinformatics of human heart failure.
Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.


Intercellular communication is required for trap formation in the nematode-trapping fungus Duddingtonia flagrans.
Nematode-trapping fungi (NTF) are a large and diverse group of fungi, which may switch from a saprotrophic to a predatory lifestyle if nematodes are present. Different fungi have developed different trapping devices, ranging from adhesive cells to constricting rings. After trapping, fungal hyphae penetrate the worm, secrete lytic enzymes and form a hyphal network inside the body. We sequenced the genome of Duddingtonia flagrans, a biotechnologically important NTF used to control nematode populations in fields. The 36.64 Mb genome encodes 9,927 putative proteins, among which are more than 638 predicted secreted proteins. Most secreted proteins are lytic enzymes, but more than 200 were classified as small secreted proteins (< 300 amino acids). 117 putative effector proteins were predicted, suggesting interkingdom communication during the colonization. As a first step to analyze the function of such proteins or other phenomena at the molecular level, we developed a transformation system, established the fluorescent proteins GFP and mCherry, adapted an assay to monitor protein secretion, and established gene-deletion protocols using homologous recombination or CRISPR/Cas9. One putative virulence effector protein, PefB, was transcriptionally induced during the interaction. We show that the mature protein is able to be imported into nuclei in Caenorhabditis elegans cells. In addition, we studied trap formation and show that cell-to-cell communication is required for ring closure. The availability of the genome sequence and the establishment of many molecular tools will open new avenues to studying this biotechnologically relevant nematode-trapping fungus.


AIDS health education for intravenous drug users.
Intravenous (IV) drug users are the second largest risk group for AIDS and the main source of infection for heterosexual partner and pediatric AIDS cases. IV drug users have an addiction and a subculture that make risk reduction difficult; for example, to refuse to share needles can endanger personal relationships, and carrying clean works (rather than renting them in a shooting gallery) risks arrest. In New York City, at least, knowledge about AIDS transmission is widespread among IV drug users, and most drug injectors report having changed their drug use practices to reduce their risks. The main functions of health education in areas where IV drug users have this level of knowledge are to disseminate news of new discoveries; reach those drug users who have not yet learned AIDS basics; reinforce what is already known; and provide information about new programs to help drug users deal with AIDS-related problems. To encourage behavior change requires going beyond simple education, however; it entails trying to change IV drug user subculture. Drug user groups in the Netherlands and in New York City are attempting to do this from within the subculture. Outside intervention requires repeated messages from multiple sources; face-to-face, interactive communication; and perhaps the use of ex-addicts as health educators.


Adaptive deep brain stimulation in Parkinson's disease.
Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application.


Potential of liraglutide in the treatment of patients with type 2 diabetes.
Liraglutide is a long-acting analog of GLP-1, being developed by Novo Nordisk and currently undergoing regulatory review for the treatment of type 2 diabetes. Upon injection, liraglutide binds non-covalently to albumin, giving it a pharmacokinetic profile suitable for once-daily administration. In clinical trials of up to 1 year duration, liraglutide has been demonstrated to have beneficial effects on islet cell function, leading to improvements in glycemic control. Both fasting and postprandial glucose concentrations are lowered, and are associated with lasting reductions in HbA1c levels. Liraglutide is effective as monotherapy and in combination therapy with oral antidiabetic drugs, and reduces HbA1c by up to approximately 1.5% from baseline (8.2%-8.4%). Because of the glucose-dependency of its action, there is a low incidence of hypoglycemia. Liraglutide is associated with body weight loss, and reductions in systolic blood pressure have been observed throughout the clinical trials. The most common adverse events reported with liraglutide are gastrointestinal (nausea, vomiting and diarrhea). These tend to be most pronounced during the initial period of therapy and decline with time. Further clinical experience with liraglutide will reveal its long-term durability, safety and efficacy.


Towards an energetic landscape: broad-scale accelerometry in woodland caribou.
Energetic balance is a central driver of individual survival and population change, yet estimating energetic costs in free- and wide-ranging animals presents a significant challenge. Animal-borne activity monitors (using accelerometer technology) present a promising method of meeting this challenge and open new avenues for exploring energetics in natural settings. To determine the behaviours and estimated energetic costs associated with a given activity level, three captive reindeer (Rangifer tarandus tarandus) at the Toronto Zoo were fitted with collars and observed for 53 h. Activity patterns were then measured over 13 months for 131 free-ranging woodland caribou (R. t. caribou) spanning 450,000 km(2) in northern Ontario. The captive study revealed a positive but decelerating relationship between activity level and energetic costs inferred from previous behavioural studies. Field-based measures of activity were modelled against individual displacement, vegetation abundance (Normalized Difference Vegetation Index), snow depth and temperature, and the best fit model included all parameters and explained over half of the variation in the data. Individual displacement was positively related to activity levels, suggesting that broad differences in energetic demands are influenced by variation in movement rates. After accounting for displacement, activity was highest at intermediate levels of vegetation abundance, presumably due to foraging behaviour. Snow depth, probably associated with digging for winter forage, moderately increased activity. Activity levels increased significantly at the coldest winter temperatures, suggesting the use of behavioural thermoregulation by caribou. These interpretations of proximate causal factors should be regarded as hypotheses subject to validation under normal field conditions. These results illustrate the landscape characteristics that increase energetic demands for caribou and confirm the great potential for the use of accelerometry in studies of animal energetics.


Melioidosis as an emerging global problem.
There is remarkably little known about the incidence of melioidosis outside a few countries (Thailand, Australia, Singapore and Malaysia). Presumably it is widespread in tropical south east Asia. Elsewhere there are tantalising glimpses of the tip of what may be a large iceberg. Since a specific diagnosis of melioidosis requires awareness on the part of clinicians, and the existence of a laboratory capable of isolating and identifying Burkholderia pseudomallei, a luxury not available in most rural tropical areas, the size of this iceberg is likely to remain unknown for the foreseeable future. There is mounting evidence that the disease is endemic in the Indian sub-continent and the Caribbean, and there have been unsubstantiated reports of recent cases in South Africa and the Middle East. It is unclear whether melioidosis has really spread to such areas relatively recently, or has been there but unrecognised for a long time. Almost all cases diagnosed in temperate climates have been imported from the tropics, with the exception of a unique outbreak which occurred in France in the mid-1970s. With increasing world wide travel of both humans and other animals, the potential exists for melioidosis to spread to new and fertile pastures.


Associations of different isomeric forms of serum lycopene with cardiovascular-disease and all-cause mortality.
Background: The effect of serum lycopene on the progression of cardiovascular diseases (CVDs) and their longevity remains a controversial topic. The purpose of this study was to evaluate the associations of different isomeric forms of serum lycopene with CVD and all-cause mortality in the American population. Methods: The National Health and Nutrition Examination Survey (NHANES) is a large population survey to investigate public health in the US. We analyzed data from 2003-2006 linked with mortality data obtained in 2015. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the risk of CVD and all-cause mortality caused by serum lycopene. Results: Among 7452 participants (aged 20-85 years, 46.7% male), 298 died from CVDs among the total 1213 deaths during a median follow-up of 10.7 years. Serum lycopene is a protective factor for all-cause and CVD mortality. In multivariable-adjusted models, the hazard ratio (with 95% confidence intervals) associated with Q4 compared to Q1 of serum total-lycopene, trans-lycopene and cis-lycopene was 0.49 (0.38,0.63), 0.49 (0.39,0.63) and 0.55 (0.43,0.70) for all-cause mortality (Ptrend<0.05), and was 0.53 (0.32,0.96), 0.48 (0.32,0.72) and 0.63 (0.41,0.97) for CVD mortality (Ptrend<0.05). The subgroup analyses showed that different isomeric forms of lycopene showed varied associations with CVD and all-cause mortality based on age, drinking status, history of hypertension and diabetes. Conclusions: Serum lycopene concentration was significantly associated with the risk of CVD and all-cause mortality. Cis-lycopene had a U-shaped relationship with mortality, while trans-lycopene had an inverse relationship with it.


Capitation adjustment for pediatric populations.
The objective of this study is to assess the predictive performance of current claims-based capitation adjustment methods for pediatric populations. Medicaid programs and other insurers may increasingly use these systems for capitation rate setting, physician profiling, and other purposes. Five leading models, a demographic model, ambulatory care groups, ambulatory diagnostic groups, diagnostic cost groups, and payment amounts for capitated systems, were tested by using use and expenditure data for children enrolled in the Maryland Medicaid program and a private nonprofit health maintenance organization in Minnesota. The models were tested at the individual level by using multiple regression methods and at the group level by using split-half validation to create both random and nonrandom groups. One of the nonrandom groups was created to represent children with chronic conditions. The findings indicate that although each of the alternative methods offers an improvement over a demographic model, significant underpayment remained for high-risk children, regardless of the capitation adjustment method used. It is concluded that children with chronic conditions would probably remain at risk for discrimination in a competitive health care market under all models tested. Limitations associated with current alternatives suggest the need for further research in the area of pediatric capitation adjustment methods.


Awareness of dying: it needs words.
The purpose of this research is to study to what extent dying patients are aware of the imminence of death, whether such awareness is associated with patient characteristics, symptoms and acceptance of dying, and whether medical records and nurses' and family caregivers' views on patients' awareness of dying agree. Nurses and family caregivers of 475 deceased patients from three different care settings in the southwest Netherlands were requested to fill out questionnaires. The two groups were asked whether a patient had been aware of the imminence of death. Also, medical records were screened for statements indicating that the patient had been informed of the imminence of death. Nurses completed questionnaires about 472 patients, family caregivers about 280 patients (response 59%). According to the medical records, 51% of patients had been aware of the imminence of death; according to nurses, 58%; according to family caregivers, 62%. Patients who, according to their family caregiver, had been aware of the imminence of death were significantly more often in peace with dying and felt more often that life had been worth living. Inter-rater agreement on patients' awareness of dying was fair (Cohen's kappa = 0.23-0.31). Being aware of dying is associated with acceptance of dying, which supports the idea that open communication in the dying phase can contribute to the quality of the dying process. However, views on whether or not patients are aware of the imminence of death diverge between different caregivers. This suggests that communication in the dying phase of patients is open for improvement.


An unprecedented high nuclearity catecholato-based Ti(IV)-architecture bearing labile pyridine ligands.
We describe the synthesis and characterisation of a robust S4-symmetry titanium-based architecture bearing catecholato and pyridine ligands. This neutral complex formulated as [Ti10O12(cat)8(py)8] displays a tetrahedral inorganic core decorated by catecholato ligands with unusual coordination modes. In solution, the pyridine ligands are labile as shown in DOSY studies at variable temperature. The light absorption property in the visible domain (λmax = 411 nm, ε = 10 800) was also characterised for the complex.


A patient presenting with diffuse cutaneous leishmaniasis (DCL) as a first indicator of HIV infection in India.
Opportunistic parasitic infections such as leishmaniasis are common in human immunodeficiency virus (HIV)-infected patients and are usually acquired several days after initial diagnosis of HIV infection. Here, we report on a patient who presented with diffuse cutaneous leishmaniasis (DCL) caused by Leishmania tropica as the first and only clinical manifestation of HIV infection. To the best of our knowledge, this is the first case that illustrates that DCL could be the first clinical indicator of HIV infection. Cutaneous leishmaniasis (CL) and DCL are becoming frequent opportunistic infections in HIV-infected individuals throughout the world. To date, all documented cases of CL and HIV coinfections have been reported in patients who were known cases of HIV and who subsequently developed CL. In this report, we present a case that illustrates that DCL could be the first clinical indicator of HIV infection.


Brain activity in advantageous and disadvantageous situations: implications for reward/punishment sensitivity in different situations.
This study modeled win and lose trials in a simple gambling task to examine the effect of entire win-lose situations (WIN, LOSS, or TIE) on single win/lose trials and related neural underpinnings. The behavior responses and brain activities of 17 participants were recorded by an MRI scanner while they performed a gambling task. Different conditions were compared to determine the effect of the task on the behavior and brain activity of the participants. Correlations between brain activity and behavior were calculated to support the imaging results. In win trials, LOSS caused less intense posterior cingulate activity than TIE. In lose trials, LOSS caused more intense activity in the right superior temporal gyrus, bilateral superior frontal gyrus, bilateral anterior cingulate, bilateral insula cortex, and left orbitofrontal cortex than WIN and TIE. The experiences of the participants in win trials showed great similarity among different win-lose situations. However, the brain activity and behavior responses of the participants in lose trials indicated that they experienced stronger negative emotion in LOSS. The participants also showed an increased desire to win in LOSS than in WIN or TIE conditions.


Paranemic Crossover DNA: There and Back Again.
Over the past 35 years, DNA has been used to produce various nanometer-scale constructs, nanomechanical devices, and walkers. Construction of complex DNA nanostructures relies on the creation of rigid DNA motifs. Paranemic crossover (PX) DNA is one such motif that has played many roles in DNA nanotechnology. Specifically, PX cohesion has been used to connect topologically closed molecules, to assemble a three-dimensional object, and to create two-dimensional DNA crystals. Additionally, a sequence-dependent nanodevice based on conformational change between PX and its topoisomer, JX2, has been used in robust nanoscale assembly lines, as a key component in a DNA transducer, and to dictate polymer assembly. Furthermore, the PX motif has recently found a new role directly in basic biology, by possibly serving as the molecular structure for double-stranded DNA homology recognition, a prominent feature of molecular biology and essential for many crucial biological processes. This review discusses the many attributes and usages of PX-DNA-its design, characteristics, applications, and potential biological relevance-and aims to accelerate the understanding of PX-DNA motif in its many roles and manifestations.


A meta-synthesis of women's experiences of cesarean birth.
The cesarean birth rate has increased dramatically over the past 10 years. With such a large number of women having a cesarean birth, it is important to understand the woman's experience of a cesarean birth and postoperative recovery. A meta-synthesis was conducted to allow for a deeper interpretation of prior qualitative research findings and thus produce a more comprehensive understanding of women's emotional and physical needs when having a cesarean birth. Qualitative studies that were published between 2000 and 2010 and were about women's experiences with cesarean births were eligible. A meta-synthesis of 10 qualitative studies was conducted. The studies created a combined sample of 3,721 nulliparous and multiparous women, 16 to 43 years of age. The following six overarching themes emerged: scared to death, in your hands, out of control, broken body and soul, empty heart and arms, and shattered dreams. It is important for healthcare professionals to realize women experience similar physical and emotional difficulties irrespective of whether the cesarean was emergent or planned. The overarching themes of (a) in your hands and (b) scared to death reveal the importance of assessing the woman's level of knowledge about cesarean birth throughout the pregnancy so misconceptions can be rectified and correct information can be provided. Healthcare professionals need to be aware of the differences in perspectives about the care provided.


Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease.
This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender. Participants with a clinical diagnosis of AD (n = 7625) were obtained from the National Alzheimer's Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs. TBI-) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset. Estimated AD onset differed by TBI history and Apoe4 independently (p's < .001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI- group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p = .34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (MDifference = 2.8 and 2.7 years, respectively). These results remained unchanged when stratified by gender. History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear.


A prerotational, simulation-based workshop improves the safety of central venous catheter insertion: results of a successful internal medicine house staff training program.
The purpose of this study was to evaluate the effectiveness of a simulation-based workshop with ultrasonography instruction in reducing mechanical complications associated with central venous catheter (CVC) insertion. A single-center prospective cohort study was conducted in the medical ICU and respiratory step-down unit of an urban teaching hospital. Fifty-six medical house staff members were trained prior to their rotations over a 6-month period. The data on mechanical complication rates after the implementation of the workshop were compared with previous experience when no structured educational program existed. There were 334 procedures in the preeducation period compared to 402 procedures in the posteducation period. The overall complication rate, including placement failure, in the preeducation and posteducation period was 32.9% and 22.9%, respectively (P < .01). Placement failure rate decreased from 22.8% to 16.2% (P = .02), and arterial punctures decreased from 4.2% to 1.5% (P = .03). Ultrasonography usage increased from 3.0% to 61.4% (P < .01). Multivariate analysis demonstrated that interns were more likely to cause overall mechanical complications compared with fellows and attending physicians in the preeducation period (P = .02); however, this trend was not observed in the posteducation period. Catheter site and ultrasonography usage significantly affected the overall complication rate in both periods, and ultrasound-guided femoral CVC was the safest procedure in the posteducation period. Implementation of a prerotational workshop significantly improved the safety of CVC insertion, especially for CVCs placed by inexperienced operators. We suggest that simulation-based training with ultrasonography instruction should be conducted if house staff members are responsible for CVC placement.


Wound anatomy after type 1 Boston KPro using oversized back plates.
To compare the anatomy of the graft-host junction and anterior chamber angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and standard (8.5-mm) back plates. Six patients with 9.5-mm titanium back plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior segment optical coherence tomography 6 to 12 months after KPro placement. The location of the graft-host junction in relation to the back plate, the corneal thickness at the graft-host junction, and the anterior chamber angle were assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM) formation in this cohort were retrospectively evaluated. The oversized back plates completely covered the graft-host junction in all quadrants, allowing the complete apposition of the posterior surface of the carrier graft with the host cornea, with decreased graft-host junction wound thickness. The standard back plates covered the posterior aspect of the carrier graft but not the graft-host junction or the host cornea, resulting in a significantly thicker graft-host junction. None of the patients with larger back plates developed a significant RPM during a 12-month follow-up period. One patient with a larger back plate developed a corneal melt at the KPro stem as a result of chronic exposure. Oversized KPro back plates effectively cover the graft-host junction without any adverse effects on angle anatomy or wound healing. This may be a strategy to provide better wound apposition, reduce RPM formation, and reduce angle closure from iris synechiae to the wound.


Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial.
Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18-60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013).


Dynamic protein associations define two phases of IL-1beta transcriptional activation.
IL-1beta is a key proinflammatory cytokine with roles in multiple diseases. Monocytes package the IL-1beta promoter into a "poised architecture" characterized by a histone-free transcription start site and constitutive transcription factor associations. Upon LPS stimulation, multiple proteins inducibly associate with the IL-1beta gene. To understand how the complex combination of constitutive and inducible transcription factors activate the IL-1beta gene from a poised structure, we measured temporal changes in NF-kappaB and IFN regulatory factor (IRF) association with IL-1beta regulatory elements. Association of the p65 subunit of NF-kappaB peaks 30-60 min post-monocyte stimulation, and it shortly precedes IRF-4 recruitment to the IL-1beta enhancer and maximal mRNA production. In contrast, IRF-8/enhancer association decreases poststimulation. To test the importance of delayed IRF-4/enhancer association, we introduced a mutated PU.1 protein shown to prevent PU.1-mediated IRF-4 recruitment to the enhancer sequence. Mutated PU.1 initially increased IL-1beta mRNA followed by decreased mRNA levels 2-3 h poststimulation. Taken together, these data support a dynamic model of IL-1beta transcriptional activation in which a combination of IRF-8 and p65 drives the initial phase of IL-1beta transcription, while PU.1-mediated IRF-4 recruitment to the enhancer is important for the second phase. We further demonstrate that activation of both NF-kappaB and IRF-4 depends on CK2 kinase activity. Because IRF-4/enhancer association requires CK2 but not p65 activation, we conclude that CK2 triggers the IRF-4 and p65 pathways independently to serve as a master regulator of IL-1beta transcription.


Functional characterization of cohesin subunit SCC1 in Trypanosoma brucei and dissection of mutant phenotypes in two life cycle stages.
In yeast and metazoa, structural maintenance of chromosome (SMC) complexes play key roles in chromosome segregation, architecture and DNA repair. The main function of the cohesin complex is to hold replicated sister chromatids together until segregation at anaphase, which is dependent on proteolytic cleavage of the cohesin subunit SCC1. Analysis of trypanosomatid genomes showed that the core cohesin and condensin complexes are conserved, but SMC5/6 is absent. To investigate the functional conservation of cohesin in eukaryotes distantly related to yeast and metazoa, we characterized the Trypanosoma brucei SCC1 orthologue. TbSCC1 is expressed prior to DNA synthesis at late G1, remains in the nucleus throughout S- and G2-phases of the cell cycle and disappears at anaphase. Depletion of SCC1 by RNAi or expression of a non-cleavable SCC1 resulted in karyokinesis failure. Using the dominant negative phenotype of non-cleavable SCC1 we investigated checkpoint regulation of cytokinesis in response to mitosis failure at anaphase. In the absence of chromosome segregation, procyclic trypanosomes progressed through cytokinesis to produce one nucleated and one anucleate cell (zoid). In contrast, cytokinesis was incomplete in bloodstream forms, where cleavage was initiated but cells failed to progress to abscission. Kinetoplast duplication was uninterrupted resulting in cells with multiple kinetoplasts and flagella.


Abortion in the United States: incidence and access to services, 2005.
Accurate information about abortion incidence and services is necessary to monitor levels of unwanted pregnancy and women's ability to access abortion services. All known abortion providers in the United States were contacted for information about abortion services in 2004 and 2005. This information, along with data from the U.S. Census Bureau, was used to examine national and state trends in numbers of abortions and abortion rates, proportions of counties and metropolitan areas without an abortion provider, and accessibility of abortion services. An estimated 1.2 million abortions were performed in the United States in 2005, 8% fewer than in 2000. The abortion rate in 2005 was 19.4 per 1,000 women aged 15-44; this rate represents a 9% decline from 2000. There were 1,787 abortion providers in 2005, only 2% fewer than in 2000. Some 87% of U.S. counties, containing 35% of women aged 15-44, did not have an abortion provider in 2005. Early medication abortion, offered by an estimated 57% of known providers, accounted for 13% of abortions (and for 22% of abortions before nine weeks' gestation). The average amount paid for an abortion at 10 weeks was $413-after adjustment for inflation, $11 less than in 2001. The numbers of abortions and the abortion rate continued their long-term decline through 2005. Reasons for this trend are unknown but may include improved access to and use of contraceptives or decreased access to abortion services.


Chimpanzee intelligence is heritable.
The role that genes play in human intelligence or IQ has remained a point of significant scientific debate dating back to the time of Galton [1]. It has now become increasingly clear that IQ is heritable in humans, but these effects can be modified by nongenetic mechanisms [2-4]. In contrast to human IQ, until recently, views of learning and cognition in animals have largely been dominated by the behaviorist school of thought, originally championed by Watson [5] and Skinner [6]. A large body of accumulated research now demonstrates a variety of cognitive abilities in nonhuman animals and challenges traditional behaviorist interpretations of performance [7, 8]. This, in turn, has led to a renewed interest in the role that social and biological factors might play in explaining individual and phylogenetic differences in cognition [9]. Specifically, aside from early attempts to selectively breed for learning skills in rodents [10-12], studies examining the role that genetic factors might play in individual variation in cognitive abilities in nonhuman animals, particularly nonhuman primates, are scarce. Here, we utilized a modified Primate Cognitive Test Battery [13] in conjunction with quantitative genetic analyses to examine whether cognitive performance is heritable in chimpanzees. We found that some but not all cognitive traits were significantly heritable in chimpanzees. We further found significant genetic correlations between different dimensions of cognitive functioning, suggesting that the genes that explain the variability of one cognitive trait might also explain that of other cognitive traits.


The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma.
Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication. Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.


Brain magnetic resonance imaging and neuropsychologic evaluation of patients with idiopathic dilated cardiomyopathy.
We compared brain magnetic resonance imaging and neuropsychologic performance in 20 neurologically asymptomatic patients suffering from idiopathic dilated cardiomyopathy (mean age 41 [range 18-49] years) and 20 age-matched controls (mean age 38 [range 28-49] years). Patients exhibited a significantly higher rate of cerebral infarcts (20% versus 0%, p less than 0.05) and cortical (50% versus 5%, p less than 0.01) and ventricular (55% versus 15%, p less than 0.02) atrophy than controls. Accordingly, semiquantitative volumetric measurements yielded a significantly increased ventricular-to-intracranial cavity ratio in the patients (6.2 +/- 2.9% versus 4.1 +/- 1.3%, p less than 0.01). This ratio and the cortical atrophy ratings correlated positively with disease duration (r = 0.63 and 0.54, p less than 0.05). Cognitive test performance was significantly worse in patients than in controls and was most impaired in those patients with morphologic cerebral abnormalities.


Safety and Efficacy of Transcatheter Aortic Valve Replacement in the Treatment of Pure Aortic Regurgitation in Native Valves and Failing Surgical Bioprostheses: Results From an International Registry Study.
The aim of this study was to evaluate the use of transcatheter heart valves (THV) for the treatment of noncalcific pure native aortic valve regurgitation (NAVR) and failing bioprosthetic surgical heart valves (SHVs) with pure severe aortic regurgitation (AR). Limited data are available about the "off-label" use of transcatheter aortic valve replacement (TAVR) to treat pure severe AR. The study population consisted of patients with pure severe AR treated by TAVR at 18 different centers. Study endpoints were device success, early safety, and clinical efficacy at 30 days, as defined by Valve Academic Research Consortium 2 criteria. A total of 146 patients were included, 78 patients in the NAVR group and 68 patients in the failing SHV group. In the NAVR group, device success, early safety, and clinical efficacy were 72%, 66%, and 61%, respectively. Device success and clinical efficacy were significantly better with newer generation THVs compared with old-generation THVs (85% vs. 54% and 75% vs. 46%, respectively, p < 0.05); this was mainly due to less second THV implantations and a lower rate of moderate to severe paravalvular regurgitation (10% vs. 24% and 3% vs. 27%, respectively). Independent predictors of 30-day mortality were body mass index <20 kg/m2, STS surgical risk score >8%, major vascular or access complication, and moderate to severe AR. In the failing SHV group, device success, early safety, and clinical efficacy were 71%, 90%, and 77%, respectively. TAVR for pure NAVR remains a challenging condition, with old-generation THVs being associated with THV embolization and migration and significant paravalvular regurgitation. Newer generation THVs show more promising outcomes. For those patients with severe AR due to failing SHVs, TAVR is a valuable therapeutic option.


Enhancing implementation of smoke-free places: A comparative qualitative study across seven European cities.
Advocacy, resources and intersubjective reasonable arguments are known as factors that contribute to smoke-free (SF) adoption and implementation in Chinese and Anglo-Saxon places. Less is known about how the implementation of smoking bans differs across European places. The aim of this qualitative comparative study is to identify and classify the SF policy implementation processes and types undertaken at the local level in seven European cities according to the views of local bureaucrats and sub-national stakeholders. Semi-structured expert interviews (n = 56) with local decision makers and stakeholders were conducted as qualitative part of the comparative SILNE-R project in Belgium (Namur), Finland (Tampere), Germany (Hanover), the Republic of Ireland (Dublin), the Netherlands (Amersfoort), Italy (Latina), and Portugal (Coimbra). Qualitative interviews were analyzed using the framework analysis. Implementation of SF environments predominantly focuses on indoor bans or youth-related settings. Progressive-hungry (Dublin), moderate-rational (Tampere), upper-saturated (Hanover, Amersfoort), and lower saturated (Namur, Coimbra, Latina) implementation types can be distinguished. These four types differ with regards to their engagement in enhancing SF places as well as along their level of perceived tobacco de-normalization and public smoking visibility. In all municipalities SF environments are adopted at national levels, but are differently implemented at the local level due national policy environments, enforcement strategies and the level of collaboration. Major mechanisms to expand SF regulations were found to be scientific evidence, public support, and the child protection frame. However, counter-mechanisms of closure occur if data on declining prevalence and new youth addiction trends trigger low prioritization. This study found four SF implementation types two mechanisms of progressive expansion and defensive closure. Development and enhancement of smoking bans requires a suitable national policy environment and indirect national-level support of self-governed local initiatives. Future SF policies can be enhanced by laws pertaining to places frequented by minors.


Immunology of pre-eclampsia.
Pre-eclampsia develops in stages, only the last being the clinical illness. This is generated by a non-specific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and not by reactivity to fetal alloantigens. However, maternal adaptation to fetal (paternal alloantigens) is crucial in the earlier stages. A pre-conceptual phase involves maternal tolerization to paternal antigens by seminal plasma. After conception, regulatory T cells, interacting with indoleamine 2,3-dioxygenase, together with decidual NK cell recognition of fetal HLA-C on extravillous trophoblast may facilitate placental growth by immunoregulation. Complete failure of this mechanism would cause miscarriage, while partial failure would cause poor placentation and dysfunctional uteroplacental perfusion. The first pregnancy preponderance and partner specificity of pre-eclampsia can be explained by this model. For the first time, the pathogenesis of pre-eclampsia can be related to defined immune mechanisms that are appropriate to the fetomaternal frontier. Now, the challenge is to prove the detail.


Cysteine string proteins associated with secretory granules of the rat neurohypophysis.
The properties and subcellular distribution of cysteine string proteins (csps) were analyzed in peptidergic nerve terminals of the rat neurohypophysis. Polyclonal antibodies raised against recombinant rat brain csp recognized a 36 kDa protein in isolated neurosecretosomes from the post-pituitary. After chemical deacylation, a single 27 kDa form was detected that displayed identical properties to csps in a whole-brain synaptosomal fraction. Immunoisolation demonstrated that synaptophysin and csps were located in the same vesicles. Density gradient centrifugation of postsynaptosomal supernatants of neurohypophysial homogenates revealed that csps and VAMP were present in two distinct vesicle populations. Synaptophysin was only detected in the slowly migrating population corresponding to small synaptic vesicles, whereas arginine vasopressin was present in the more rapidly sedimenting population indicating that it contains large dense core vesicles (LDCVs). Immobilized antibodies against csp, synaptotagmin, or VAMP captured vesicular arginine vasopressin confirming the association of these proteins with LDCVs. Co-immunoprecipitation assays with proteins solubilized from neurohypophysial or whole-brain nerve terminals failed to reveal complexes containing csp and [125I]omegaGVIA receptors. These results indicate that csps in the CNS are associated with both small synaptic vesicles and LDCVs. However, they do not provide support for the hypothesis that protein complexes implicated in exocytosis, which interact with presynaptic N-type calcium channels, contain csps.


Combined genetic analysis of sputum and computed tomography for noninvasive diagnosis of non-small-cell lung cancer.
CT plays an important role in diagnosis of lung cancer, however has been limited by uncertain detection rate for early stage of non-small-cell lung cancer (NSCLC), particularly central tumors. Genetic analysis of sputum has proven to be useful in diagnosis of NSCLC. We proposed to evaluate efficacy of combing CT and genetic analysis of sputum for noninvasive diagnosis of stage I NSCLC. Genomic copy changes of a panel of lung cancer-related genes, HYAL2, FHIT, p16, and SP-A were analyzed by a mini-chip in sputum from 33 patients with stage I NSCLC and 49 cancer-free controls. The genetic and CT diagnoses were compared with surgical-pathologic stage. CT had higher sensitivity (85%) in detection of lung cancer compared with the mini-chip (70%) (p<0.05), while there was no significant difference in specificity between the two tests (89% vs. 92%, p=0.09). Similarly, CT showed considerably higher sensitivity (93%) in identifying peripheral tumors than did the mini-chip (64%) (p<0.05), whereas there was no difference in specificity between them (98% vs. 96%, p=0.28). However, in detecting central tumors, CT had lower specificity (90%) compared with the mini-chip (98%) (p<0.05), although its sensitivity (79%) was higher than that of the mini-chip (73%) (p=0.05). Combining both tests offered higher sensitivity (91%) than did any single one (85%, 70%, all <0.05), while still keeping 92% sensitivity. In particular, this combined approach yielded higher sensitivity, specificity, and accuracy for diagnosing central cancers compared with CT alone (all p<0.05). The integration of the genetic assay with CT led to improvements in noninvasive diagnosis of stage I NSCLCs, especially central tumors.


Parental Presence During Treatment of Ebola or Other Highly Consequential Infection.
This clinical report offers guidance to health care providers and hospitals on options to consider regarding parental presence at the bedside while caring for a child with suspected or proven Ebola virus disease (Ebola) or other highly consequential infection. Options are presented to help meet the needs of the patient and the family while also posing the least risk to providers and health care organizations. The optimal way to minimize risk is to limit contact between the person under investigation or treatment and family members/caregivers whenever possible while working to meet the emotional support needs of both patient and family. At times, caregiver presence may be deemed to be in the best interest of the patient, and in such situations, a strong effort should be made to limit potential risks of exposure to the caregiver, health care providers, and the community. The decision to allow parental/caregiver presence should be made in consultation with a team including an infectious diseases expert and state and/or local public health authorities and should involve consideration of many factors, depending on the stage of investigation and management, including (1) a careful history, physical examination, and investigations to elucidate the likelihood of the diagnosis of Ebola or other highly consequential infection; (2) ability of the facility to offer appropriate isolation for the person under investigation and family members and to manage Ebola; (3) ability to recognize and exclude people at increased risk of worse outcomes (eg, pregnant women); and (4) ability of parent/caregiver to follow instructions, including appropriate donning and doffing of personal protective equipment.


Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system.
Quantifying pathogen transmission in multi-host systems is difficult, as exemplified in bovine tuberculosis (bTB) systems, but is crucial for control. The agent of bTB, Mycobacterium bovis, persists in cattle populations worldwide, often where potential wildlife reservoirs exist. However, the relative contribution of different host species to bTB persistence is generally unknown. In Britain, the role of badgers in infection persistence in cattle is highly contentious, despite decades of research and control efforts. We applied Bayesian phylogenetic and machine-learning approaches to bacterial genome data to quantify the roles of badgers and cattle in M. bovis infection dynamics in the presence of data biases. Our results suggest that transmission occurs more frequently from badgers to cattle than vice versa (10.4x in the most likely model) and that within-species transmission occurs at higher rates than between-species transmission for both. If representative, our results suggest that control operations should target both cattle and badgers.


Neural crest-derived tumor neuroblastoma and melanoma share 1p13.2 as susceptibility locus that shows a long-range interaction with the SLC16A1 gene.
Neuroblastoma (NB) and malignant cutaneous melanoma (CMM) are neural crest cells (NCC)-derived tumors and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association studies (GWAS). We took a three-staged approach to conduct cross-disease meta-analysis of GWAS for NB and CMM (2101 NB cases and 4202 controls; 12 874 CMM cases and 23 203 controls) to identify shared loci. Findings were replicated in 1403 NB cases and 1403 controls of European ancestry and in 636 NB, 508 CMM cases and 2066 controls of Italian origin. We found a cross-association at locus 1p13.2 (rs2153977, odds ratio = 0.91, P = 5.36 × 10-8). We also detected a suggestive (P < 10-7) NB-CMM cross-association at 2q37.1 with opposite effect on cancer risk. Pathway analysis of 110 NB-CMM risk loci with P < 10-4 demonstrated enrichment of biological processes such as cell migration, cell cycle, metabolism and immune response, which are essential of human NCC development, underlying both tumors. In vitro and in silico analyses indicated that the rs2153977-T protective allele, located in an NB and CMM enhancer, decreased expression of SLC16A1 via long-range loop formation and altered a T-box protein binding site. Upon depletion of SLC16A1, we observed a decrease of cellular proliferation and invasion in both NB and CMM cell lines, suggesting its role as oncogene. This is the largest study to date examining pleiotropy across two NC cell-derived tumors identifying 1p13.2 as common susceptibility locus for NB and CMM risk. We demonstrate that combining genome-wide association studies results across cancers with same origins can identify new loci common to neuroblastoma and melanoma arising from tissues which originate from neural crest cells. Our results also show 1p13.2 confer risk to neuroblastoma and melanoma by regulating SLC16A1.


Cytotoxic T lymphocytes and viral adaptation in HIV infection.
Cytotoxic T lymphocytes are central in determining the extent of immune control of HIV infection. We examine the degree to which one may trace the steps that underlie these human leucocyte antigen/disease outcome associations. These findings will be of relevance to HIV vaccine design. Initial investigations suggested that immune escape was inevitably associated with loss of control of viral replication. Recent studies of successful immune control of HIV infection, however, indicate that immune selection pressure on the virus may in certain circumstances result in viral adaptation with a reduced replication capacity. The dominant influence of particular human leucocyte antigen B alleles on HIV disease outcome is echoed in hepatitis C infection, and major histocompatibility complex class I alleles in the non-human primate that are associated with control of simian immunodeficiency virus infection also share similar mechanisms of viral control. Cytotoxic T lymphocyte-mediated selection pressure on HIV has important consequences for subsequent immune control within the host. The extent to which viral adaptation occurs in the general population to alter these consequences is complex and epitope-specific, but is critical to the ongoing effectiveness of particular cytotoxic T lymphocyte responses through the course of the epidemic.


Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.
Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.


FaDu cell characteristics induced by multidrug resistance.
The major obstacle to tumor chemotherapy is drug resistance. In the present study, we investigated the characteristics of FaDu cells (a hypopharyngeal carcinoma cell line) with multidrug resistance (MDR) induced by Taxol. The resistant cell line, FaDu/T, was grown by exposing normal FaDu cells to escalating concentrations of Taxol stepwise for over 12 months. The multidrug resistant sensitivities of the FaDu/T cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) were investigated by methyl-thiazolyl-tetrazolium (MTT) assay. Cell apoptosis was measured by acridine orange and Hoechst 33342/propidium iodide double staining. Cell cycle distribution and the cell apoptosis index were quantified using flow cytometry. Reverse transcription-polymerase chain reaction (RT-PCR) was conducted to determine the mRNA levels of the MDR-related genes MDR1/ABCB1 and BCRP/ABCG2. Western blotting was used to assay the expression of MDR1/ABCB1 and BCRP/ABCG2 and the apoptosis-related proteins caspase-3, Bcl-2 and Bax. Compared with the FaDu cells, the drug resistance of FaDu/T cells to DDP, 5-FU, Dox and VCR was increased 8.99-, 21.96-, 31.42- and 10.00-fold, respectively. The percentages of FaDu/T cells in the G0/G1 and G2/M phases were increased while the cell percentage in the S phase decreased as compared with the percentages of FaDu cells. The anti-apoptotic ability increased prominently, as the index of apoptosis decreased. Furthermore, caspase-3, Bcl-2 and Bax expression was altered accordingly to resist apoptosis in the FaDu/T cells. MDR1/ABCB1 expression increased significantly at both the mRNA and protein levels, while BCRP/ABCG2 expression appeared to inversely affected, i.e. decreased, in a concentration-dependent manner. These -findings may provide theoretical support for the prevention of MDR in clinical cancer chemotherapy.


Activation of learned action sequences by auditory feedback.
The present research addressed whether auditory feedback associated with a learned action sequence can activate the action representation of that sequence. Nonpianist participants learned to perform two melodies at a piano keyboard repeatedly during a trial. The participants heard feedback either from the melody they were performing (normal feedback) or from the other learned melody (termed alternate feedback). An additional tone functioned as an instruction cue to either switch melodies or continue the current melody. Following the instruction cues, participants typically paused just before switching, and paused similarly during trials with a continue cue. Participants paused longer after a continue cue when they experienced alternate rather than normal feedback. This effect was specific to instruction cues positioned at weak metrical accents--positions at which participants were less likely to switch overall. Feedback did not influence timing on switch trials. These findings indicate that influences of auditory feedback can activate learned action sequences, leading to longer latencies associated with cue evaluation.


Does parents' socio-economic status matter in intentions of vaccinating against human papillomavirus for adolescent daughters?
The Human Papilloma Virus (HPV) vaccination provides substantial protection, and it is best to be taken before the age of twelve. Taiwan approved HPV vaccines since 2006. However, very few female adolescent have been vaccinated until now. To examine whether the parents' socio-economic status matters in deciding to purchase HPV vaccination for their daughters based on the theory of planned behavior. A structured questionnaire to collect 394 responses from parents of adolescent girls in Taiwan. Data was coded to categorize relevant socio-economic classes, and was analyzed with SPSS. The behavior intentions of parents with low (mean= 5.28) and high (5.01) socio-economic status are significantly stronger than the moderate (4.56) in deciding to purchase the HPV vaccination. Socio-economic factor has a slightly negative impact (B= -0.08), and attitude (0.68), subjective norms (0.16), and behavior control (0.32) have positive impacts on the parents' intention. Major impacts on the decision to purchase an HPV vaccination for their adolescent was not due to the parents' socio-economic status but the parent's attitude. As the major predictor of a less complicated decision, attitudes toward the HPV vaccination should be reinforced through continuous communications between service providers and patient-advocate groups.


Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.
Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.


Big data, big knowledge: big data for personalized healthcare.
The idea that the purely phenomenological knowledge that we can extract by analyzing large amounts of data can be useful in healthcare seems to contradict the desire of VPH researchers to build detailed mechanistic models for individual patients. But in practice no model is ever entirely phenomenological or entirely mechanistic. We propose in this position paper that big data analytics can be successfully combined with VPH technologies to produce robust and effective in silico medicine solutions. In order to do this, big data technologies must be further developed to cope with some specific requirements that emerge from this application. Such requirements are: working with sensitive data; analytics of complex and heterogeneous data spaces, including nontextual information; distributed data management under security and performance constraints; specialized analytics to integrate bioinformatics and systems biology information with clinical observations at tissue, organ and organisms scales; and specialized analytics to define the "physiological envelope" during the daily life of each patient. These domain-specific requirements suggest a need for targeted funding, in which big data technologies for in silico medicine becomes the research priority.


I could have done otherwise: Availability of counterfactual comparisons informs the sense of agency.
Personal control and agency are closely associated with the counterfactual notion that a person could have done otherwise (CDO). In both philosophy and law, this counterfactual evaluation determines responsibility and punishment, yet little is known about its influence on agents' experience during action. We used a risky decision-making task to study how counterfactual evaluations influenced participants' sense of agency. Two factors were manipulated independently: the presence/absence of counterfactual comparisons between actions and the presence/absence of counterfactual comparisons between outcomes of these actions. Perceived agency was highest when both counterfactual comparisons were available. Interestingly, this pattern persisted even when counterfactual information was only revealed after action, suggesting a purely reconstructive evaluation effect. These findings allow a more precise phrasing of the CDO element of personal agency: a person feels most control when she could have performed another action, thereby obtaining another outcome.


Influence of quasi-specific sites on kinetics of target DNA search by a sequence-specific DNA-binding protein.
Functions of transcription factors require formation of specific complexes at particular sites in cis-regulatory elements of genes. However, chromosomal DNA contains numerous sites that are similar to the target sequences recognized by transcription factors. The influence of such "quasi-specific" sites on functions of the transcription factors is not well understood at present by experimental means. In this work, using fluorescence methods, we have investigated the influence of quasi-specific DNA sites on the efficiency of target location by the zinc finger DNA-binding domain of the inducible transcription factor Egr-1, which recognizes a 9 bp sequence. By stopped-flow assays, we measured the kinetics of Egr-1's association with a target site on 143 bp DNA in the presence of various competitor DNAs, including nonspecific and quasi-specific sites. The presence of quasi-specific sites on competitor DNA significantly decelerated the target association by the Egr-1 protein. The impact of the quasi-specific sites depended strongly on their affinity, their concentration, and the degree of their binding to the protein. To quantitatively describe the kinetic impact of the quasi-specific sites, we derived an analytical form of the apparent kinetic rate constant for the target association and used it for fitting to the experimental data. Our kinetic data with calf thymus DNA as a competitor suggested that there are millions of high-affinity quasi-specific sites for Egr-1 among the 3 billion bp of genomic DNA. This study quantitatively demonstrates that naturally abundant quasi-specific sites on DNA can considerably impede the target search processes of sequence-specific DNA-binding proteins.


Garcinia dulcis Fruit Extract Induced Cytotoxicity and Apoptosis in HepG2 Liver Cancer Cell Line.
Garcinia dulcis or locally known in Malaysia as "mundu" belongs to the family of Clusiaceae. The study was conducted to investigate the anticancer potential of different parts of G. dulcis fruit extracts and their possible mechanism of action in HepG2 liver cancer cell line. MTT assay showed that the peel, flesh, and seed extracts of G. dulcis induced cytotoxicity in HepG2 cell line with IC50 values of 46.33 ± 4.51, 38.33 ± 3.51, and 7.5 ± 2.52 µg/mL, respectively. The flesh extract of G. dulcis induced cell cycle arrest at sub-G1 (apoptosis) phase in a time-dependent manner. Staining with Annexin V-FITC and propidium iodide showed that 41.2% of the cell population underwent apoptosis after 72 hours of exposure of the HepG2 cell line to G. dulcis flesh extract. Caspase-3 has been shown to be activated which finally leads to the death of HepG2 cell (apoptosis). GC-MS analysis showed that the highest percentage of compound identified in the extract of G. dulcis flesh was hydroxymethylfurfural and 3-methyl-2,5-furandione, together with xanthones and flavonoids (based on literature), could synergistically contribute to the observed effects. This finding suggested that the flesh extract of G. dulcis has its own potential as cancer chemotherapeutic agent against liver cancer cell.


Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course: A Report from an International CMSC Consensus Conference, March 5-7, 2010.
It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5 to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS.


ESX/type VII secretion systems and their role in host-pathogen interaction.
The ESX-1 system is responsible for the secretion of the prototypic ESX proteins, namely the 6 kDa early secreted antigenic target (ESAT-6) and the 10 kDa culture filtrate protein (CFP-10). These two proteins, which form a 1:1 heterodimeric complex, are among the most important proteins of Mycobacterium tuberculosis involved in host-pathogen interaction. They induce a strong T cell mediated immune response, are apparently involved in membrane and/or host-cell lysis and represent key virulence factors. There are four other paralogous ESX systems in M. tuberculosis, some of which are essential for in vitro growth. ESX systems also exist in many other actinobacteria and Gram-positive bacteria, and have recently been suggested to be named type VII secretion systems.


Genomic newborn screening: public health policy considerations and recommendations.
The use of genome-wide (whole genome or exome) sequencing for population-based newborn screening presents an opportunity to detect and treat or prevent many more serious early-onset health conditions than is possible today. The Paediatric Task Team of the Global Alliance for Genomics and Health's Regulatory and Ethics Working Group reviewed current understanding and concerns regarding the use of genomic technologies for population-based newborn screening and developed, by consensus, eight recommendations for clinicians, clinical laboratory scientists, and policy makers. Before genome-wide sequencing can be implemented in newborn screening programs, its clinical utility and cost-effectiveness must be demonstrated, and the ability to distinguish disease-causing and benign variants of all genes screened must be established. In addition, each jurisdiction needs to resolve ethical and policy issues regarding the disclosure of incidental or secondary findings to families and ownership, appropriate storage and sharing of genomic data. The best interests of children should be the basis for all decisions regarding the implementation of genomic newborn screening.


Definition of a tumor suppressor locus within human chromosome 3p21-p22.
Cytogenetic abnormalities and high-frequency allele losses involving the short arm of human chromosome 3 have been identified in a variety of histologically different neoplasms. These findings suggest that a tumor-suppressor gene or genes may be located in the region of 3p14-p25, although there has been no definitive functional proof for the involvement of a particular region of 3p. We report a rapid genetic assay system that has allowed functional analysis of defined regions of 3p in the suppression of tumorigenicity in vivo. Interspecific microcell hybrids containing fragments of chromosome 3p were constructed and screened for tumorigenicity in athymic nude mice. Hybrid clones were obtained that showed a dramatic tumor suppression and contained a 2-megabase fragment of human chromosomal material encompassing the region 3p21 near the interface with 3p22. With these hybrid clones, we have defined a genetic locus at 3p21-p22 intimately involved in tumor suppression.


Helicobacter pylori in the dental plaque: is it of diagnostic value for gastric infection?
The aim of present study was the assessment of association of helicobacter pylori of dental plaque and stomach in a more homogenous population and also to determine the diagnostic value of dental plaque for gastric infection. Based on the results of Rapid urease test (RUT) on specimens from gastric antrum, 88 patients with symptoms of dyspepsia were assigned into two groups of infected and non-infected with helicobacter pylori. Supragingival plaque samples were collected from mandibular first and second molar area using and sterile curette and were investigated using RUT. Statistical analysis of data was performed using chi-square test and independent t-test. H. pylori was detected in 34.1 % of dental plaque specimens. The prevalence of helicobacter pylori infection in dental was 31.8 % and 36.4 % in patients with and without gastric infection (P=0.6). Also the interaction of age and infection was not significant but the prevalence of H. pylori both in the dental plaque and the stomach of male patients was higher than female patients. There is not any significant association between the helicobacter pylori of the dental plaque and the stomach. Also the dental plaque can not be used as a primary diagnostic aid for gastric infection.


Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation.
The growth of many breast tumors is stimulated by estradiol (E2), which activates a classic mechanism of regulation of gene expression and signal transduction pathways inducing cell proliferation. Polyphenols of natural origin with chemical similarity to estrogen have been shown to interfere with tumor cell proliferation. The aim of this study was to investigate whether hydroxytyrosol (HT) and oleuropein (OL), two polyphenols contained in extra-virgin olive oil, can affect breast cancer cell proliferation interfering with E2-induced molecular mechanisms. Both HT and OL inhibited proliferation of MCF-7 breast cancer cells. Luciferase gene reporter experiments, using a construct containing estrogen responsive elements able to bind estrogen receptor alpha (ERalpha) and the study of the effects of HT or OL on ERalpha expression, demonstrated that HT and OL are not involved in ERalpha-mediated regulation of gene expression. However, further experiments pointed out that both OL and HT determined a clear inhibition of E2-dependent activation of extracellular regulated kinase1/2 belonging to the mitogen activating protein kinase family. Our study demonstrated that HT and OL can have a chemo-preventive role in breast cancer cell proliferation through the inhibition of estrogen-dependent rapid signals involved in uncontrolled tumor cell growth.


Mental health and resilience at older ages: bouncing back after adversity in the British Household Panel Survey.
Resilience is having good outcomes despite adversity and risk and could be described in terms of preserving the same level of the outcome or rebounding back to that level after an initial set back. Using the latter definition, resilience as "bouncing back", this paper aims (1) to identify those members of a panel survey who demonstrated resilience, and (2) to identify the characteristics of the resilient individuals and the predictors of their resilience. The study subjects were the 3581 participants in the British Household Panel Survey, selected from waves 1-14, who satisfied three requirements: exposure to an adversity; availability of consecutive General Health Questionnaire (GHQ)-12 scores; aged 50 or more years. The primary outcome variable was resilience, operationalised as a GHQ-12 score that increased after exposure to adversity and returned to its pre-exposure level in the next (after 1 year) wave of the survey. The adversities were: functional limitation; bereavement or marital separation; poverty. The prevalence of resilience, as defined, was 14.5%. After adjusting for regression to the mean, the GHQ-12 score of the resilient dropped by a mean of 3.6 points in the post-adversity period. Women predominated among the resilient, with this gender difference stronger among older women than younger women. The resilient were more likely to have high social support than the non-resilient, but otherwise were not different socioeconomically. High social support pre-adversity and during adversity increased the likelihood of resilience by 40-60% compared with those with low social support. Resilience is relatively rare and favours older women. It is fostered by high levels of social support existing before exposure to adversity.


Is rice based oral rehydration therapy effective in young infants?
Rice based oral rehydration therapy (ORT) solutions have been shown to be superior to glucose oral rehydration salts (World Health Organisation (WHO) ORS) in reducing stool volume and duration of diarrhoea in children and adults. Rice based ORT has been used only sparingly in young infants, however, because of theoretical concerns about digestibility. A randomised controlled trial of rice based ORT (50 g rice and electrolytes identical to WHO ORS) and WHO ORS was carried out in 52 male infants less than 6 months old with moderately severe acute diarrhoea to evaluate efficacy and digestibility. Nineteen (70%) of 27 children who received rice based ORT and 18 (72%) of 25 children who received WHO ORS were treated successfully. The mean (SD) diarrhoeal stool output for the first 24 hours of treatment was significantly lower in the infants receiving the rice based ORT than in those receiving WHO ORS (101.0 (60.5) v 137.1 (74.6) g/kg). The stool output was also significantly less in the rice based ORT group in the second 24 hours. Infants in the rice based ORT group drank significantly less rehydration solution than infants in the WHO ORS group (mean (SD) 165.4 (77.4) v 217.9 (86.1) during the first 24 hours of treatment. There was no difference in the duration of diarrhoea between the groups. The volume of breast and formula feeding was similar in the two groups. No difference was seen in the frequency of finding reducing substances or acid pH in the stools of either group of children. The results suggest that rice based ORT is as effective as WHO ORS in infants with moderately severe diarrhoea and that rice based ORT is as well tolerated as WHO ORS in infants.


Examining Mid-Upper Arm Circumference Malnutrition z-Score Thresholds.
Anthropometric z-scores used commonly for diagnosis and determining degree of malnutrition, specifically body mass index (BMIz), weight-for-length (WLz), and mid-upper arm circumference (MUACz), are not wholly concordant, yet the proposed thresholds for classification are identical. This study was designed to critically examine MUACz thresholds and their ability to correctly classify nutrition status. This was a 2-year, prospective single-center study of children ≤18 years seen by registered dietitians within a large pediatric institution. The sensitivity, specificity, and predictive performance of the malnutrition classification thresholds were estimated against clinician-based classification. Sixty-one dietitians enrolled 10,401 patients with distributions of z-scores for weight (-0.5 ± 1.9), length (-0.8 ± 1.6), BMI or WL (-0.1 ± 1.8), and MUAC (-0.4 ± 1.5), suggesting participants were smaller and shorter than the reference U.S. Distributions of MUACz were broad and overlapped between nutrition classification groups, an observation that extended to BMIz and WLz as well. Consequently, existing thresholds do not accurately classify 100% of children. Misclassification rates increase, with increasing severity ranging from 8% in children with no malnutrition to 71% in children with severe malnutrition. Algorithm- and manually-based refinement of thresholds result in mixed improvements and can be explored by the reader with the associated supplement. The sensitivity of proposed MUACz thresholds systematically decreases with increasing severity of malnutrition and will require optimization if we aim to limit the number of children at risk of misclassification. Indicators for overnutrition remain to be addressed but are explored herein.


A metagenomic analysis displays the diverse microbial community of a vermicomposting system in Uganda.
Vermicomposting is a mesophilic process using earthworms to efficiently and at low cost process large volumes of organic waste. It has been suggested to not only increase soil fertility but also increase biomass of beneficial bacteria while reducing harmful bacteria. The aim of this study was to set up a strategy to investigate and characterise the viral as well as the bacterial composition of a vermicomposting system. The vermicomposting unit used in this study was placed at the Makerere University Agricultural Research Institute Kabanyolo on the outskirts of Kampala, Uganda, and was fed with 80% cattle manure and 20% food waste. On Day 172, the compost was terminated and compost samples were collected from three layers of the unit: the top, the middle and the bottom layer. A metagenomic approach was then applied to characterise the viral and bacterial composition of the vermicomposting system. A high abundance and diversity of bacteria were identified. Proteobacteria was the largest phyla in the compost (mainly Alpha-, Gamma- and Betaproteobacteria), constituting almost 65% of the bacterial reads in the data sets. DNA samples from several possible pathogenic bacteria, such as Salmonella spp., Escherichia coli, Enterobacter spp., Enterococcus spp. and Clostridium spp, were detected in the vermicompost, suggesting that there might still be harmful bacteria in the vermicast. Phages constituted the main viral group; apart from phages, mainly insect viruses were identified. The only animal or human virus identified was kobuvirus. In summary, metagenomic analysis was shown to be an efficient technology to characterise the microbial composition of vermicast. The data from this study contribute to a better understanding of the microbes present in this kind of composting system and can help determine measures necessary for safe manure handling.


Oculomotor dominance in multitasking: mechanisms of conflict resolution in cross-modal action.
In daily life, eye movement control usually occurs in the context of concurrent action demands in other effector domains. However, little research has focused on understanding how such cross-modal action demands are coordinated, especially when conflicting information needs to be processed conjunctly in different action modalities. In two experiments, we address this issue by studying vocal responses in the context of spatially conflicting eye movements (Experiment 1) and in the context of spatially conflicting manual actions (Experiment 2, under controlled eye fixation conditions). Crucially, a comparison across experiments allows us to assess resource scheduling priorities among the three effector systems by comparing the same (vocal) response demands in the context of eye movements in contrast to manual responses. The results indicate that in situations involving response conflict, eye movements are prioritized over concurrent action demands in another effector system. This oculomotor dominance effect corroborates previous observations in the context of multiple action demands without spatial response conflict. Furthermore, and in line with recent theoretical accounts of parallel multiple action control, resource scheduling patterns appear to be flexibly adjustable based on the temporal proximity of the two actions that need to be performed.