Direct economic burden of hepatitis B virus related diseases: evidence from Shandong, China.
Although the expenses of liver cirrhosis are covered by a critical illness fund under the current health insurance program in China, the economic burden associated with hepatitis B virus (HBV) related diseases is not well addressed. In order to provide evidence to address the economic disease burden of HBV, we conducted a survey to investigate the direct economic burden of acute and chronic hepatitis B, cirrhosis and liver cancer caused by HBV-related disease. From April 2010 to November 2010, we conducted a survey of inpatients with HBV-related diseases and who were hospitalized for seven or more days in one of the seven tertiary and six secondary hospitals in Shandong, China. Patients were recorded consecutively within a three-to-five month time period from each sampled hospital; an in-person survey was conducted to collect demographic and socio-economic information, as well as direct medical and nonmedical expenses during the last month and last year prior to the current hospitalization. Direct medical costs included total outpatient, inpatient, and self-treatment expenditures; direct nonmedical costs included spending on nutritional supplements, transportation, and nursing. Direct medical costs during the current hospitalization were also obtained from the hospital financial database. The direct economic cost was calculated as the sum of direct medical and nonmedical costs. Our results call for the importance of implementing clinical guideline, improving system accountability, and helping secondary and smaller hospitals to improve efficiency. This has important policy implication for the on-going hospital reform in China. Our data based on inpatients with HBV-related diseases suggested that the direct cost in US dollars for acute hepatitis B, severe hepatitis B, chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis and primary liver cancer was $2954, $10834, $4552, $7400.28, $6936 and $10635, respectively. These costs ranged from 30.72% (for acute hepatitis B) to 297.85% (for primary liver cancer) of the average annual household income in our sample. Even for patients with health insurance, direct out-of-pocket cost of all HBV-related diseases except acute hepatitis B exceeded 40.00% of the patient's disposable household income, making it a catastrophic expenditure for the household. Hepatitis B imposes considerable economic burden on a family. Our findings will help health policy makers' understanding of the magnitude of the economic burden of HBV-related diseases in China. Evidence from our study also contributes to our understanding of potential benefits to society from allocating more resources to preventing and treating HBV infection, as well as increasing insurance coverage in China. These findings have important policy implications for health care reform efforts currently underway in China focusing on how to reduce the burden of catastrophic disease for its citizens.


Promoting linguistic complexity, greater message length and ease of engagement in email writing in people with aphasia: initial evidence from a study utilizing assistive writing software.
Improving email writing in people with aphasia could enhance their ability to communicate, promote interaction and reduce isolation. Spelling therapies have been effective in improving single-word writing. However, there has been limited evidence on how to achieve changes to everyday writing tasks such as email writing in people with aphasia. One potential area that has been largely unexplored in the literature is the potential use of assistive writing technologies, despite some initial evidence that assistive writing software use can lead to qualitative and quantitative improvements to spontaneous writing. This within-participants case series design study aimed to investigate the effects of using assistive writing software to improve email writing in participants with dysgraphia related to aphasia. Eight participants worked through a hierarchy of writing tasks of increasing complexity within broad topic areas that incorporate the spheres of writing need of the participants: writing for domestic needs, writing for social needs and writing for business/administrative needs. Through completing these tasks, participants had the opportunity to use the various functions of the software, such as predictive writing, word banks and text to speech. Therapy also included training and practice in basic computer and email skills to encourage increased independence. Outcome measures included email skills, keyboard skills, email writing and written picture description tasks, and a perception of disability assessment. Four of the eight participants showed statistically significant improvements to spelling accuracy within emails when using the software. At a group level there was a significant increase in word length with the software; while four participants showed noteworthy changes to the range of word classes used. Enhanced independence in email use and improvements in participants' perceptions of their writing skills were also noted. This study provided some initial evidence that assistive writing technologies can support people with aphasia in email writing across a range of important performance parameters. However, more research is needed to measure the effects of these technologies on the writing of people with aphasia, and to determine the optimal compensatory mechanisms for specific people given the linguistic-strategic resources they bring to the task of email writing.


Real-world effectiveness, its predictors and onset of action of cholinesterase inhibitors and memantine in dementia: retrospective health record study.
The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date. We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling. The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2-5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment. This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.


Exploration of the Brain's White Matter Structure through Visual Abstraction and Multi-Scale Local Fiber Tract Contraction.
We present a visualization technique for brain fiber tracts from DTI data that provides insight into the structure of white matter through visual abstraction. We achieve this abstraction by analyzing the local similarity of tract segment directions at different scales using a stepwise increase of the search range. Next, locally similar tract segments are moved toward each other in an iterative process, resulting in a local contraction of tracts perpendicular to the local tract direction at a given scale. This not only leads to the abstraction of the global structure of the white matter as represented by the tracts, but also creates volumetric voids. This increase of empty space decreases the mutual occlusion of tracts and, consequently, results in a better understanding of the brain's three-dimensional fiber tract structure. Our implementation supports an interactive and continuous transition between the original and the abstracted representations via various scale levels of similarity. We also support the selection of groups of tracts, which are highlighted and rendered with the abstracted visualization as context.


Effects of neutralizing antibodies on escape from CD8+ T-cell responses in HIV-1 infection.
Despite substantial advances in our knowledge of immune responses against HIV-1 and of its evolution within the host, it remains unclear why control of the virus eventually breaks down. Here, we present a new theoretical framework for the infection dynamics of HIV-1 that combines antibody and CD8(+) T-cell responses, notably taking into account their different lifespans. Several apparent paradoxes in HIV pathogenesis and genetics of host susceptibility can be reconciled within this framework by assigning a crucial role to antibody responses in the control of viraemia. We argue that, although escape from or progressive loss of quality of CD8(+) T-cell responses can accelerate disease progression, the underlying cause of the breakdown of virus control is the loss of antibody induction due to depletion of CD4(+) T cells. Furthermore, strong antibody responses can prevent CD8(+) T-cell escape from occurring for an extended period, even in the presence of highly efficacious CD8(+) T-cell responses.


Different roles and viewpoints of scientific experts in advising on environmental health risks.
Environmental health risks are often complex, largescale, and uncertain. The uncertainties inherent in these problems permit differences among experts in the appraisal of risks. This raises the question of whether different expert roles exist and, if so, how this affects the policy advice that is given. Here, we present a pilot study of the different roles and viewpoints that can be discerned among scientific experts in the Netherlands. Q methodology was used to empirically explore existing theoretical treatises on different expert roles. In total, 26 electromagnetic field (EMF) experts and 21 particulate matter (PM) experts participated. The responses were analyzed separately for EMF and PM respondents using Q factor analysis. In both the EMF and PM domain, three different expert roles were identified. This suggests that particular expert roles depend on the specific environmental health risk. The results indicate that different expert roles exist among scientists who provide policy advice on environmental health risks. This empirical study adds new data and insights to the literature on expert roles. The results of this study are relevant for the selection and composition of expert committees and the interpretation of expert advice.


Rubidium and sodium permeability of the ATP-sensitive K+ channel in single rat pancreatic beta-cells.
1. The patch-clamp method has been used to study the selectivity of single ATP-sensitive potassium channels in excised membrane patches from dissociated rat pancreatic beta-cells. 2. In symmetrical K+ concentrations the current-voltage relation of this channel showed slight inward rectification. The K+ permeability coefficient was 1.05 x 10(-13) cm3/s ([K+]o = 140 mM; 20 degrees C) in the inside-out patch and somewhat smaller when measured under the same conditions in the outside-out configuration (0.86 x 10(-13) cm3/s). 3. When intracellular Rb+ replaced K+, inward K+ currents were unaffected but the outward currents carried by Rb+ were substantially smaller. The extent of the reduction in the outward currents depended on the internal Rb+/K+ ratio and increased as [Rb+]i was raised. Both inward and outward Rb+ currents were blocked by 1 mM-ATP. No currents were measurable in symmetrical 140 mM-Rb+ solutions. 4. With 140 mM [K+]o and 140 mM [Rb+]i the single-channel current-voltage relation reversed at +8 mV and the potential at which the variance of the ATP-sensitive current was least was shifted by 6 mV to more positive potentials. These data suggest a PRb/PK ratio of around 0.7. 5. Outward Rb+ currents were reduced at all potentials in inside-out patches exposed to 107 mM-Rb+ solution intracellularly and 5 mM-K+ externally. 6. Partial replacement of external K+ with Rb+ substantially reduced the inward currents recorded from outside-out patches and also decreased outward K+ currents. 7. In outside-out patches, the addition of 1 mM-Rb+ to the external solution produced a block of inward K+ currents that initially increased and then decreased again with hyperpolarization. This suggests that the Rb+ block of K+ currents is voltage dependent and that Rb+ acts as a permeant blocker of K+ currents. 8. The sodium permeability of the channel, relative to that of potassium, was 0.39 for internal Na+ and 0.007 for external Na+ ions. 9. We conclude that Rb+ serves as an acceptable tracer for K+ in efflux studies when changes in K+ flux through ATP-sensitive K+ channels are of interest but that the magnitude of such fluxes will be considerably underestimated.


Validation and human factor analysis study of an infant weight estimation device.
Weight is critical for the medical management of infants; however, scales can be unavailable or inaccessible in some practice settings. We recently developed and validated a robust infant weight estimation method based on chest circumference (CC) and head circumference (HC). This study was designed to determine the human factors (HF) experience with, and predictive performance of, an infant weight estimation device that implements this method. Prospective, multi-center, observational, masked study of 486 preterm and term infants (0-90 days) assessed by 15 raters. Raters measured the infant using calibrated scales/measures and masked versions of the device. Raters also evaluated critical tasks associated with device use. Mean error (ME) and mean percentage error (MPE) were used to assess predictive performance. Among 486 infants enrolled (36.8 ± 4.0 weeks gestational age, 31.5 ± 28.6 days postnatal age), predicted weight correlated highly with actual weight (r = 0.97, ME: - 69 ± 257 g, MPE: - 1.3 ± 6.9%). Predicted weight was within 10 and 15% of actual weight in 86 and 99%, of infants. HF errors were low, 0.1-0.8% depending on task. In all cases raters were confident or very confident in their measurements. The device was statistically equivalent to the method on which it was based and approximated weight with acceptable variance from the true weight. HF data suggest the device is easy to use. This device can be used to estimate weight in infants when calibrated scales are impractical or unavailable.


Inorganic nanotubes reinforced polyvinylidene fluoride composites as low-cost electromagnetic interference shielding materials.
Novel polymer nanocomposites comprising of MnO2 nanotubes (MNTs), functionalized multiwalled carbon nanotubes (f-MWCNTs), and polyvinylidene fluoride (PVDF) were synthesized. Homogeneous distribution of f-MWCNTs and MNTs in PVDF matrix were confirmed by field emission scanning electron microscopy. Electrical conductivity measurements were performed on these polymer composites using four probe technique. The addition of 2 wt.% of MNTs (2 wt.%, f-MWCNTs) to PVDF matrix results in an increase in the electrical conductivity from 10-16S/m to 4.5 × 10-5S/m (3.2 × 10-1S/m). Electromagnetic interference shielding effectiveness (EMI SE) was measured with vector network analyzer using waveguide sample holder in X-band frequency range. EMI SE of approximately 20 dB has been obtained with the addition of 5 wt.% MNTs-1 wt.% f-MWCNTs to PVDF in comparison with EMI SE of approximately 18 dB for 7 wt.% of f-MWCNTs indicating the potential use of the present MNT/f-MWCNT/PVDF composite as low-cost EMI shielding materials in X-band region.


Population genetic structure and isolation by distance of Helicobacter pylori in Senegal and Madagascar.
Helicobacter pylori has probably infected the human stomach since our origins and subsequently diversified in parallel with their human hosts. The genetic population history of H. pylori can therefore be used as a marker for human migration. We analysed seven housekeeping gene sequences of H. pylori strains isolated from 78 Senegalese and 24 Malagasy patients and compared them with the sequences of strains from other geographical locations. H. pylori from Senegal and Madagascar can be placed in the previously described HpAfrica1 genetic population, subpopulations hspWAfrica and hspSAfrica, respectively. These 2 subpopulations correspond to the distribution of Niger-Congo speakers in West and most of subequatorial Africa (due to Bantu migrations), respectively. H. pylori appears as a single population in Senegal, indicating a long common history between ethnicities as well as frequent local admixtures. The lack of differentiation between these isolates and an increasing genetic differentiation with geographical distance between sampling locations in Africa was evidence for genetic isolation by distance. The Austronesian expansion that started from Taiwan 5000 years ago dispersed one of the 10 subgroups of the Austronesian language family via insular Southeast Asia into the Pacific and Madagascar, and hspMaori is a marker for the entire Austronesian expansion. Strain competition and replacement of hspMaori by hpAfrica1 strains from Bantu migrants are the probable reasons for the presence of hspSAfrica strains in Malagasy of Southeast Asian descent. hpAfrica1 strains appear to be generalist strains that have the necessary genetic diversity to efficiently colonise a wide host spectrum.


[Ketamine's antidepressant effect: literature review on clinical use].
Depressive disorders have a major impact on public health. They are prevalent and disabling, with high economic burden for society. Antidepressants have a delayed action and at least one third of patients do not achieve adequate response. The recent discovery of ketamine's unique antidepressant properties, with rapid onset of response and high rate of responders opens new perspectives for treatment-resistant depression (TRD). The aim of this article is to summarize preclinical trials and clinical trials demonstrating ketamine antidepressant properties and to review the different modalities of use. Most clinical studies used ketamine with a single subanesthetic intravenous administration in patients with treatment-resistant depression, demonstrating a rapid but transient antidepressant response with high response rates. To prevent relapse and maintain the initial benefits, few studies have shown the interest of serial infusions of ketamine, while others combined ketamine and electroconvulsive therapy using the former as an anesthetic. So far, relay treatments with glutamatergic agents such as riluzole are disappointing. Although most studies were conducted in patients with TRD in recurrent depression or bipolar disorder, efficacy in acutely suicidal patients is promising. Our review highlights the increasing interest in the use of ketamine in the treatment of treatment-resistant depression. Although a widespread use of ketamine as an antidepressant in routine clinical settings seems limited by psychotomimetic effects and the lack of strategy to maintain initial benefits, ketamine or related drugs might be used to target specific conditions, such as bipolar depression or high suicide risk.


MR Image Reconstruction Using Block Matching and Adaptive Kernel Methods.
An approach to Magnetic Resonance (MR) image reconstruction from undersampled data is proposed. Undersampling artifacts are removed using an iterative thresholding algorithm applied to nonlinearly transformed image block arrays. Each block array is transformed using kernel principal component analysis where the contribution of each image block to the transform depends in a nonlinear fashion on the distance to other image blocks. Elimination of undersampling artifacts is achieved by conventional principal component analysis in the nonlinear transform domain, projection onto the main components and back-mapping into the image domain. Iterative image reconstruction is performed by interleaving the proposed undersampling artifact removal step and gradient updates enforcing consistency with acquired k-space data. The algorithm is evaluated using retrospectively undersampled MR cardiac cine data and compared to k-t SPARSE-SENSE, block matching with spatial Fourier filtering and k-t ℓ1-SPIRiT reconstruction. Evaluation of image quality and root-mean-squared-error (RMSE) reveal improved image reconstruction for up to 8-fold undersampled data with the proposed approach relative to k-t SPARSE-SENSE, block matching with spatial Fourier filtering and k-t ℓ1-SPIRiT. In conclusion, block matching and kernel methods can be used for effective removal of undersampling artifacts in MR image reconstruction and outperform methods using standard compressed sensing and ℓ1-regularized parallel imaging methods.


[Outcome of elderly patients in an intensive care unit in Dakar, Senegal].
To determine the frequency of admission and its reasons, severity and outcome among elderly patients in our intensive care unit (ICU) and compare them with those for younger subjects. Retrospective study covering a 5-year period (January 1, 2005, through December 31, 2009) in the ICU of the principal hospital in Dakar. We included as elderly patients all those aged at least 65 years and compared them with the young patients, that is, those younger than 65 years. During the study period, 2196 patients were admitted to the ICU, 374 of them elderly. The ratio of men to women was 1.43. The mean age among the elderly was 74.4 ± 6.5 years, and their mean duration of ICU stay was 5.6 ± 4.67 days. Nearly 80% had a serious medical history or preexisting condition, most often, myocardial infarction, stroke, or lung disease. The older patients were more seriously ill than the younger ones (p<0.01), but their care was less complex. Mortality was higher among the older, compared with the younger, subjects (42.80% vs. 28.4%). The only mortality-related factor that appeared to vary with age was cardiogenic pulmonary edema. The management of elderly subjects remains a problem in intensive care. High mortality is generally not directly related to their age but rather to their overall condition.


Socio-Demographic Correlates of Total and Domain-Specific Sedentary Behavior in Latin America: A Population-Based Study.
The aim of this study was to identify socio-demographic correlates of total and domain-specific sedentary behavior (SB). Cross-sectional findings are based on 9218 participants (15-65 years) from the Latin American Study of Nutrition and Health. Data were collected between September 2014 and February 2015. Participants reported time spent in SB across specific domains. Sex, age, ethnicity, socioeconomic (SEL), and education level were used as sociodemographic indicators. Participants spent a total of 373.3 min/day engaged in total SB. Men, younger adults, other ethnicities, higher SEL and educational level presented higher total SB when compared with women, older adults, white/Caucasian, and low SEL and educational level. Men spent more time on the playing videogames (b: 32.8: 95% CI: 14.6;51.1) and riding in an automobile (40.5: 31.3; 49.8). Computer time, reading, socializing or listening to music was higher in younger participants (<30 years) compared with those ≥50 years in the total sample. Compared to the low SEL and educational level groups, middle (11.7: 5.7; 17.6) and higher (15.1: 5.3; 24.9) SEL groups as well as middle (9.8: 3.6; 15.9) and higher (16.6: 6.5; 26.8) education level groups reported more time spent reading. Socio-demographic characteristics are associated with SB patterns (total and specific) across Latin American countries.


Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study.
N-linked glycosylation is one of the most important, chemically complex, and ubiquitous post-translational modifications in all eukaryotes. The N-glycans that are covalently linked to proteins are involved in numerous biological processes. There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties. In this study, the impacts of N-glycans on protein structure and dynamics are systematically investigated using an integrated computational approach of the Protein Data Bank structure analysis and atomistic molecular dynamics simulations of glycosylated and deglycosylated proteins. Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability. Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.


Assessment of the COBAS Amplicor HBV Monitor Test for quantitation of serum hepatitis B virus DNA levels.
Treatment of patients with chronic hepatitis B virus (HBV) infections with potent antiviral therapy often results in dramatic reductions in the levels of viremia to very low levels. Monitoring of serum HBV DNA levels is a consistent method for the assessment of antiviral potency; however, widely used hybridization assays for the monitoring of HBV DNA levels have limited sensitivities and are not effective for the monitoring of patients whose serum HBV DNA levels have decreased to below approximately 700,000 HBV genomes/ml. The objective of the present study was to assess a PCR-based assay (the COBAS-AM assay) for quantitation of serum HBV DNA levels and to compare the results of the COBAS-AM assay with those of a solution hybridization assay with a radiolabeled probe. The precision and accuracy of the assay were determined with low-positive and high-positive controls consisting of a plasmid DNA molecule containing HBV-specific primer binding regions, and the sensitivity of the assay was determined by using serial dilutions of sera from subjects with chronic HBV infection. HBV DNA levels were quantitated in 1,695 serum samples from subjects with chronic HBV infection who were enrolled in clinical trials of lamivudine in North America or Asia. The COBAS-AM assay demonstrated high levels of inter- and intra-assay precision and accuracy, and the linear range of the COBAS-AM assay was greater than that of the solution hybridization assay. The assay is linear over a 3-log(10) range and is able to quantitate serum HBV DNA at levels 3 log(10) lower than those that can be detected by the solution hybridization assay. We found that the COBAS-AM assay is an accurate PCR-based assay for quantitation of serum HBV DNA levels in subjects with chronic HBV infection.


Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep.
Leaders from the Canadian Society for Exercise Physiology convened representatives of national organizations, content experts, methodologists, stakeholders, and end-users who followed rigorous and transparent guideline development procedures to create the Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These novel guidelines for children and youth aged 5-17 years respect the natural and intuitive integration of movement behaviours across the whole day (24-h period). The development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument and systematic reviews of evidence informing the guidelines were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Four systematic reviews (physical activity, sedentary behaviour, sleep, integrated behaviours) examining the relationships between and among movement behaviours and several health indicators were completed and interpreted by expert consensus. Complementary compositional analyses were performed using Canadian Health Measures Survey data to examine the relationships between movement behaviours and health indicators. A stakeholder survey was employed (n = 590) and 28 focus groups/stakeholder interviews (n = 104) were completed to gather feedback on draft guidelines. Following an introductory preamble, the guidelines provide evidence-informed recommendations for a healthy day (24 h), comprising a combination of sleep, sedentary behaviours, light-, moderate-, and vigorous-intensity physical activity. Proactive dissemination, promotion, implementation, and evaluation plans have been prepared in an effort to optimize uptake and activation of the new guidelines. Future research should consider the integrated relationships among movement behaviours, and similar integrated guidelines for other age groups should be developed.


Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia.
Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. This article is part of a Special Issue entitled SI: Brain and Memory.


Longitudinal study of Plasmodium falciparum and Plasmodium vivax in a Karen population in Thailand.
Clinical case treatment of malaria infections where Plasmodium falciparum and Plasmodium vivax are sympatric has achieved effective reductions in P. falciparum prevalence and incidence rates, but has been less successful for P. vivax. The high transmissibility of P. vivax and its capacity to relapse have been suggested to make it a harder parasite species to control. A clinical malaria case treatment programme was carried out over a decade in a Karen community composed of seven hamlets on the Thai-Myanmar border. From 1994 to 2004, prevalence rates of both P. falciparum and P. vivax decreased by 70-90% in six of the seven study hamlets, but were unchanged in one hamlet. Overall, incidence rates decreased by 72% and 76% for P. falciparum and P. vivax respectively over the period 1999-2004. The age-incidence and prevalence curves suggested that P. vivax was more transmissible than P. falciparum despite a greater overall burden of infection with P. falciparum. Male gender was associated with increased risk of clinical presentation with either parasite species. Children (< 15 years old) had an increased risk of presenting with P. vivax but not P. falciparum. There was a considerable reduction in incidence rates of both P. vivax and P. falciparum over a decade following implementation of a case treatment programme. The concern that intervention methods would inadvertently favour one species over another, or even lead to an increase in one parasite species, does not appear to be fulfilled in this case.


Lignipirellula cremea gen. nov., sp. nov., a planctomycete isolated from wood particles in a brackish river estuary.
A novel planctomycetal strain, designated Pla85_3_4T, was isolated from the surface of wood incubated at the discharge of a wastewater treatment plant in the Warnow river near Rostock, Germany. Cells of the novel strain have a cell envelope architecture resembling that of Gram-negative bacteria, are round to pear-shaped (length: 2.2 ± 0.4 µm, width: 1.2 ± 0.3 µm), form aggregates and divide by polar budding. Colonies have a cream colour. Strain Pla85_3_4T grows at ranges of 10-30 °C (optimum 26 °C) and at pH 6.5-10.0 (optimum 7.5), and has a doubling time of 26 h. Phylogenetically, strain Pla85_3_4T (DSM 103796T = LMG 29741T) is concluded to represent a novel species of a novel genus within the family Pirellulaceae, for which we propose the name Lignipirellula cremea gen. nov., sp. nov.


Distance education to prepare nursing faculty in Eritrea: diffusion of an innovative model of midwifery education.
The World Health Organization has identified 56 countries with critical health care provider shortages. This article describes an innovative collaboration between Stony Brook University, Stony Brook, NY, and the University of Asmara, Eritrea, aimed at increasing the number of qualified nursing faculty in Eritrea. Eritrean graduate nursing students used distance education technologies and in-country clinical support to complete a program of study that prepared them for an advanced practice nursing and faculty role. The 10 students were all highly successful and graduated in 4 semesters. These students and the Stony Brook faculty who supported them from the United States provided feedback and recommendations for future programming. The article provides key recommendations to other universities considering distance education collaboration to help build nursing capacity in developing countries. First, ensure bilateral understanding of the differences between the health care and educational systems in the partner countries. Second, select appropriate educational technology considering both technical and human factors. Third, ensure that students and faculty are sufficiently prepared for success. Fourth, maintain a strong focus on clinical education. Finally, remain flexible through program implementation, working together with students to adjust the program to address local needs and challenges.


Reservoir competence of native North American birds for the lyme disease spirochete, Borrelia burgdorfieri.
Reservoir competence for the Lyme disease spirochete, Borrelia burgdorferi, was tested for six species of native North American birds: American robin, gray catbird, brown thrasher, eastern towhee, song sparrow, and northern cardinal. Wild birds collected by mist netting on Fire Island, NY, were held in a field laboratory in cages over water and locally collected larval ticks were placed on the birds, harvested from the water after engorgement, and tested for infection by direct fluorescentantibody staining after molting to the nymphal stage. American robins were competent reservoirs, infecting 16.1% of larvae applied to wild-caught birds, compared with 0% of control ticks placed on uninfected laboratory mice. Robins that were previously infected in the laboratory by nymphal feeding infected 81.8% of applied larvae. Wild-caught song sparrows infected 4.8% of applied larvae and 21.1% when infected by nymphal feeding. Results suggest moderate levels of reservoir competence for northern cardinals, lower levels for gray catbirds, and little evidence of reservoir competence for eastern towhees or brown thrashers. Lower infection rates in larvae applied to wild-caught birds compared with birds infected in the laboratory suggest that infected birds display temporal variability in infectiousness to larval ticks. Engorged larvae drop from birds abundantly during daylight, so the abundance of these bird species in the peridomestic environment suggests that they might contribute infected ticks to lawns and gardens.


Pollutant removal efficacy of three wet detention ponds.
Monthly inflow and outflow data were collected from three wet detention ponds in Wilmington, North Carolina, for a 29-mo period. Two ponds drained urban areas consisting primarily of residential, mixed services, and retail usage, while the third mainly drained residential and golf course areas. One of the urban ponds achieved significant reductions in total nitrogen, nitrate, ammonium, total phosphorus, orthophosphate, and fecal coliform bacterial counts. This pond was characterized by a high length to width ratio, with most inputs directed into the upper area, and extensive coverage by a diverse community of aquatic macrophyte vegetation. The second urban pond achieved significant reductions in turbidity and fecal coliform bacterial counts, but there were no significant differences between inflowing and outflowing water nutrient concentrations. There were substantial suburban runoff inputs entering the mid- and lower-pond areas that short-circuited pollutant removal contact time. The golf course pond showed significant increases in nitrate, ammonium, total phosphorus, and orthophosphate in the outflow relative to the inflow, probably as a result of course fertilization. However, nutrient concentrations in the outflow water were low compared with discharges from a selection of other area golf courses, possibly a result of the outflow passing through a wooded wetland following pond discharge. To achieve good reduction in a variety of pollutants, wet pond design should include maximizing the contact time of inflowing water with rooted vegetation and organic sediments. This can be achieved through a physical pond design that provides a high length to width ratio, and planting of native macrophyte species.


Antimurine antibody formation following OKT3 therapy.
OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)


Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma.
Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.


Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Unlike other malignancies, TP53 mutations are rare in MPM. Recent studies have showed that altered expression of microRNA (miRNA) is observed in human malignant tumors. In this study, we investigated the alterations of miR-34s, a direct transcriptional target of TP53, and the role of miR-34s on the pathogenesis of MPM. Aberrant methylation and expression of miR-34s were examined in MPM cell lines and tumors. miR-34b/c was transfected to MPM cells to estimate the protein expression, cell proliferation, invasion, and cell cycle. Aberrant methylation was present in 2 (33.3%) of 6 MPM cell lines and 13 (27.7%) of 47 tumors in miR-34a and in all 6 MPM cell lines (100%) and 40 (85.1%) of 47 tumors in miR-34b/c. Expression of miR-34a and 34b/c in all methylated cell lines was reduced and restored with 5-aza-2'-deoxycytidine treatment. Because epigenetic silencing was the major event in miR-34b/c, we investigated the functional role of miR-34b/c in MPM. miR-34b/c-transfected MPM cells with physiologic miR-34b/c expression exhibited antiproliferation with G(1) cell cycle arrest and suppression of migration, invasion, and motility. The forced overexpression of miR-34b/c, but not p53, showed a significant antitumor effect with the induction of apoptosis in MPM cells. We show that the epigenetic silencing of miR-34b/c by methylation is a crucial alteration and plays an important role in the tumorigenesis of MPM, suggesting potential therapeutic options for MPM.


The Impact of Different Animal-Derived Protein Sources on Adiposity and Glucose Homeostasis during Ad Libitum Feeding and Energy Restriction in Already Obese Mice.
Low-fat diets and energy restriction are recommended to prevent obesity and to induce weight loss, but high-protein diets are popular alternatives. However, the importance of the protein source in obesity prevention and weight loss is unclear. The aim of this study was to investigate the ability of different animal protein sources to prevent or reverse obesity by using lean or obese C57BL/6J mice fed high-fat/high-protein or low-fat diets with casein, cod or pork as protein sources. Only the high-fat/high-protein casein-based diet completely prevented obesity development when fed to lean mice. In obese mice, ad libitum intake of a casein-based high-fat/high-protein diet modestly reduced body mass, whereas a pork-based high-fat/high-protein diet aggravated the obese state and reduced lean body mass. Caloric restriction of obese mice fed high-fat/high-protein diets reduced body weight and fat mass and improved glucose tolerance and insulin sensitivity, irrespective of the protein source. Finally, in obese mice, ad libitum intake of a low-fat diet stabilized body weight, reduced fat mass and increased lean body mass, with the highest loss of fat mass found in mice fed the casein-based diet. Combined with caloric restriction, the casein-based low-fat diet resulted in the highest loss of fat mass. Overall, the dietary protein source has greater impact in obesity prevention than obesity reversal.


Genetic differences in anticonvulsant sensitivity in mouse lines selectively bred for ethanol withdrawal severity.
WSP (withdrawal seizure-prone) mice exhibit approximately 10-fold more severe withdrawal convulsions than WSR (withdrawal seizure-resistant) mice after identical chronic ethanol exposure. Although WSP and WSR mice do not differ in threshold for seizures elicited by electroconvulsive shock (ECS), WSR mice are more sensitive to ethanol-induced elevation of ECS seizure thresholds. The current experiments demonstrated that WSR mice showed more ECS-induced seizure threshold elevation than WSP mice when tested after the administration of C1-C5 straight-chain alcohols. Whereas the brain concentrations of the C1 and C2 alcohols did not differ between the lines, WSP mice tended to have higher brain concentrations than WSR mice of the C3-C5 alcohols, even though they exhibited the smaller behavioral response in all cases. Thus, the difference between WSP and WSR mice was one of neurosensitivity and could not be attributed to pharmacokinetic differences. The WSR line was also more sensitive to ethchlorvynol, methyprylon, barbital, phenobarbital, pentobarbital, diazepam, valproic acid and phenytoin in this test. Examining loss of righting reflex (RR), we found that WSP and WSR mice did not differ in ED50, latency to lose RR or duration of loss of RR. Thus, the genetic anticonvulsant sensitivity difference is not simply a genetic difference in sensitivity to central nervous system depression between the lines. In summary, WSR mice were more sensitive to the anticonvulsant effects of a variety of compounds than WSP mice, suggesting that some genes influence both ethanol withdrawal seizures and ethanol's anticonvulsant effects.


Infant Feeding and Risk of Type 1 Diabetes in Two Large Scandinavian Birth Cohorts.
Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes. We included two population-based cohorts of children followed from birth (1996-2009) to 2014 (Denmark) or 2015 (Norway). We analyzed data from a total of 155,392 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC). Parents reported infant dietary practices when their child was 6 and 18 months old. The outcome was clinical type 1 diabetes, ascertained from nationwide childhood diabetes registries. Hazard ratios (HRs) were estimated using Cox regression. Type 1 diabetes was identified in 504 children during follow-up, and the incidence of type 1 diabetes per 100,000 person-years was 30.5 in the Norwegian cohort and 23.5 in the Danish cohort. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed (HR 2.29 [95% CI 1.14-4.61] for no breastfeeding vs. any breastfeeding for ≥12 months). Among those who were breastfed, however, the incidence of type 1 diabetes was independent of duration of both full breastfeeding (HR per month 0.99 [95% CI 0.97-1.01]) and any breastfeeding (0.97 [0.92-1.03]). Suggestive evidence supports the contention that breastfeeding reduces the risk of type 1 diabetes. Among those who were breastfed, however, no evidence indicated that prolonging full or any breastfeeding was associated with a reduced risk of type 1 diabetes.


Initiating Maintenance Dialysis Before Living Kidney Donor Transplantation When a Donor Candidate Evaluation Is Well Underway.
Preemptive kidney transplants result in better outcomes and patient experiences than transplantation after dialysis onset. It is unknown how often a person initiates maintenance dialysis before living kidney donor transplantation when their donor candidate evaluation is well underway. Using healthcare databases, we retrospectively studied 478 living donor kidney transplants from 2004 to 2014 across 5 transplant centers in Ontario, Canada, where the recipients were not receiving dialysis when their donor's evaluation was well underway. We also explored some factors associated with a higher likelihood of dialysis initiation before transplant. A total of 167 (35%) of 478 persons with kidney failure initiated dialysis in a median of 9.7 months (25th-75th percentile, 5.4-18.7 months) after their donor candidate began their evaluation and received dialysis for a median of 8.8 months (3.6-16.9 months) before kidney transplantation. The total cohort's dialysis cost was CAD $8.1 million, and 44 (26%) of 167 recipients initiated their dialysis urgently in hospital. The median total donor evaluation time (time from evaluation start to donation) was 10.6 months (6.4-21.6 months) for preemptive transplants and 22.4 months (13.1-38.7 months) for donors whose recipients started dialysis before transplant. Recipients were more likely to start dialysis if their donor was female, nonwhite, lived in a lower-income neighborhood, and if the transplant center received the recipient referral later. One third of persons initiated dialysis before receiving their living kidney donor transplant, despite their donor's evaluation being well underway. Future studies should consider whether some of these events can be prevented by addressing inappropriate delays to improve patient outcomes and reduce healthcare costs.


Long-term disability after lacunar stroke: secondary prevention of small subcortical strokes.
To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke. SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0-14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile. Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85-0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75-2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001). In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.


Acanthamoeba-cytopathic protein induces apoptosis and proinflammatory cytokines in human corneal epithelial cells by cPLA2α activation.
We have shown that Acanthamoeba interacts with a mannosylated protein on corneal epithelial cells and stimulates trophozoites to secrete a mannose-induced 133 kDa protease (MIP-133), which facilitates corneal invasion and induces apoptosis. The mechanism of MIP-133-induced apoptosis is unknown. The aim of this study was to determine if MIP-133 induces apoptosis and proinflammatory cytokines/chemokines in human corneal epithelial (HCE) cells via the cytosolic phospholipase A(2α) (cPLA(2α)) pathway. HCE cells were incubated with or without MIP-133 at doses of 7.5, 15, and 50 μg/mL for 6, 12, and 24 hours. The effects of cPLA(2α) inhibitors on cPLA(2α), arachidonic acid (AA) release, and apoptosis were tested in vitro. Inhibition of cPLA(2α) involved preincubating HCE cells for 1 hour with cPLA(2α) inhibitors (10 μM methyl-arachidonyl fluorophosphonate [MAFP] or 20 μM arachidonyl trifluoromethyl ketone [AACOCF3]) with or without MIP-133 for 24 hours. Expression of cPLA(2α) mRNA and enzyme was examined by RT-PCR and cPLA(2) activity assays, respectively. Apoptosis of corneal epithelial cells was determined by caspase-3 and DNA fragmentation assays. Expression of IL-8, IL-6, IL-1β, and IFN-γ was examined by RT-PCR and ELISA. MIP-133 induced significant cPLA(2α) (approximately two to four times) and AA release (approximately six times) from corneal cells while cPLA(2α) inhibitors significantly reduced cPLA(2α) (approximately two to four times) and AA release (approximately three times) (P < 0.05). cPLA(2α) inhibitors significantly inhibited MIP-133-induced DNA fragmentation approximately 7 to 12 times in HCE cells (P < 0.05). MIP-133 specifically activates cPLA(2α) enzyme activity in HCE cells, which is blocked by preincubation with anti-MIP-133 antibody. In addition, MIP-133 induced significant IL-8, IL-6, IL-1β, and IFN-γ production, approximately two to three times (P < 0.05). MIP-133 interacts with phospholipids on plasma membrane of HCE cells and activates cPLA(2α). cPLA(2α) is involved in apoptosis, AA release, and activation of proinflammatory cytokines/chemokines from HCE cells. cPLA(2α) inhibitors may be a therapeutic target in Acanthamoeba keratitis.


Should scientists be required to use a model-based solution to adjust for possible distance-based detectability bias?
The most popular method used to gain an understanding of population trends or of differences in bird abundance among land condition categories is to use information derived from point counts. Unfortunately, various factors can affect one's ability to detect birds, and those factors need to be controlled or accounted for so that any difference in one's index among time periods or locations is an accurate reflection of differences in bird abundance and not differences in detectability. Avian ecologists could use appropriately sized fixed-area surveys to minimize the chance that they might be deceived by distance-based detectability bias, but the current method of choice is to use a modeling approach that allows one to account for distance-based bias by modeling the effects of distance on detectability or occupancy. I challenge the idea that modeling is the best approach to account for distance-based effects on the detectability of birds because the most important distance-based modeling assumptions can never be met. The use of a fixed-area survey method to generate an index of abundance is the simplest way to control for distance-based detectability bias and should not be universally condemned or be the basis for outright rejection in the publication process.


Hippocampal and cortical atrophy in amyloid-negative mild cognitive impairments: comparison with amyloid-positive mild cognitive impairment.
Although patients with amnestic mild cognitive impairment (aMCI) are at higher risk of developing Alzheimer's disease (AD), their pathologies could be heterogeneous. We aimed to evaluate structural changes in amyloid-negative and amyloid-positive aMCI patients. Forty-eight aMCI patients who underwent Pittsburgh compound B (PiB) positron emission tomography were recruited. They were classified as PiB (-) aMCI (N = 16) and PiB (+) (N = 32). Hippocampal shape and regional cortical thickness were compared with 41 subjects with normal cognition (NC). Relative to NC, PiB(-) aMCI exhibited hippocampal deformity in the right cornu ammonis 1, whereas PiB(+) aMCI exhibited hippocampal deformity in bilateral subiculum and cornu ammonis 1 subregions. Relative to NC, PiB(-) aMCI showed cortical thinning in the left medial prefrontal and right anterior temporal regions, whereas PiB(+) aMCI exhibited cortical thinning in bilateral medial temporal regions, temporoparietal junctions and precuneus, and prefrontal cortices. Our findings suggest that structural changes in PiB(-) aMCI might be due to several possible pathologic changes, whereas structural changes in PiB(+) aMCI reflect AD-like structural changes.


Diversity-Oriented Approach to N-Heterocyclic Compounds from α-Phenyl-β-enamino Ester via a Mitsunobu-Michael Reaction Sequence.
Herein we delineate a novel route for the diastereoselective construction of diversely substituted N-heterocyclic ring systems as valuable scaffolds for natural products and pharmaceuticals, starting from an easily accessible prochiral α-phenyl-β-enamino ester. The reaction sequence relies on the unexplored reactivity of α-phenyl-β-enamino ester as a nucleophilic partner in the Mitsunobu reaction to forge the N-tethered alkene-alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero-Michael addition reaction under mild conditions to furnish the respective N-heterocyclic compounds embedded with an exocyclic chiral center in high yields and excellent diastereoselectivities. The methodology is amenable for a broad range of substrates based on a metal-free approach.


A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.


The potential hazards of xenotransplantation: an overview.
Xenotransplantation, in particular the transplantation of pig cells, tissues and organs into human recipients, may alleviate the current shortage of suitable allografts available for human transplantation. This overview addresses the physiological, immunological and microbial factors involved in xenotransplantation. The issues reviewed include the merits of using pigs as xenograft source species, the compatibility of pig and human organ physiology, and the rejection mechanism and attempts to overcome this immunological challenge. The authors discuss advances in the prevention of pig organ rejection through the creation of genetically modified pigs, more suited to the human micro-environment. Finally, in regard to microbial hazards, the authors review possible viral infections originating from pigs.


The proportion of youths' physical inactivity attributable to neighbourhood built environment features.
We investigated the independent association between several neighbourhood built environment features and physical inactivity within a national sample of Canadian youth, and estimated the proportion of inactivity within the population that was attributable to these built environment features. This was a cross-sectional study of 6626 youth aged 11-15 years from 272 schools across Canada. Participants resided within 1 km of their school. Walkability, outdoor play areas (parks, wooded areas, yards at home, cul-de-sacs on roads), recreation facilities, and aesthetics were measured objectively within each school neighbourhood using geographic information systems. Physical inactivity (<5 days/week of 60 minutes of moderate-to-vigorous physical activity) was assessed by questionnaire. Multilevel logistic regression analyses, which controlled for several covariates, examined relationships between built environment features and physical inactivity. The final regression model indicated that, by comparison to youth living in the least walkable neighbourhoods, the risks for physical inactivity were 28-44% higher for youth living in neighbourhoods in the remaining three walkability quartiles. By comparison to youth living in neighbourhoods with the highest density of cul-de-sacs, risks for physical inactivity were 28-32% higher for youth living in neighbourhoods in the lowest two quartiles. By comparison to youth living in neighbourhoods with the least amount of park space, risks for physical inactivity were 28-37% higher for youth living in the neighbourhoods with a moderate to high (quartiles 2 and 3) park space. Population attributable risk estimates suggested that 23% of physical inactivity within the population was attributable to living in walkable neighbourhoods, 16% was attributable to living in neighbourhoods with a low density of cul-de-sacs, and 15% was attributable to living in neighbourhoods with a moderate to high amount of park space. Of the neighbourhood built environment exposure variables measured in this study, the three that were the most highly associated with inactivity were walkability, the density of cul-de-sacs, and park space. The association between some of these features and youths' activity levels were in the opposite direction to what has previously been reported in adults and younger children.


Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury.
Opening of cardiac ATP-sensitive potassium channels (K(ATP) channels) is a well-characterized protective mechanism against ischemia and reperfusion injury. Evidence exists for an involvement of both sarcolemmal and mitochondrial K(ATP) channels in such protection. Classically, cardiac sarcolemmal K(ATP) channels are thought to be composed of Kir6.2 (inward-rectifier potassium channel 6.2) and SUR2A (sulfonylurea receptor type 2A) subunits; however, the evidence is strong that SUR1 (sulfonylurea receptor type 1) subunits are also expressed in the heart and that they may have a functional role. The aim of this study, therefore, was to examine the role of SUR1 in myocardial infarction. We subjected mice lacking SUR1 subunits to in vivo myocardial ischemia/reperfusion injury. Interestingly, the SUR1-null mice were markedly protected against the ischemic insult, displaying a reduced infarct size and preservation of left ventricular function, which suggests a role for this K(ATP) channel subunit in cardiovascular function during conditions of stress. SUR1 subunits have a high sensitivity toward many sulfonylureas and certain K(ATP) channel-opening drugs. Their potential role during ischemic events should therefore be considered both in the interpretation of experimental data with pharmacological agents and in the clinical arena when the cardiovascular outcome of patients treated with antidiabetic sulfonylureas is being considered.


Poor performance of current prognostic scores for early risk of recurrence after minor stroke.
The ABCD(2) score predicts the early risk of stroke after transient ischemic attack. The early risk of recurrence after minor stroke is as high but the only validated prognostic scores for use in minor stroke predict long-term risk of recurrence: the Essen Stroke Risk Score and the Stroke Prognosis Instrument II. We determined the prognostic value of the ABCD(2) score, Essen Stroke Risk Score, and Stroke Prognosis Instrument II in a prospective population-based study in Oxfordshire, UK, of all incident and recurrent stroke (Oxford Vascular Study). Minor stroke was defined as an National Institutes of Health Stroke Scale score ≤5 at the time of first assessment. The 90-day risks of recurrent stroke were determined in relation to each score. Areas under the receiver operator curves indicated predictive value. Of 1247 first events in the study period, 488 were transient ischemic attacks, 520 were minor strokes, and 239 were major strokes. The ABCD(2) score was modestly predictive (area under the receiver operator curve, 0.64; 0.53 to 0.74; P=0.03) of recurrence at 7 days after minor stroke and at 90 days (0.62; 0.54 to 0.70; P=0.004). Neither Essen Stroke Risk Score (0.50; 0.42 to 0.59; P=0.95) nor Stroke Prognosis Instrument II (0.48; 0.39 to 0.60; P=0.92) were predictive of 7-day or 90-day risk of recurrent stroke. Of the traditional vascular risk factors, etiologic classification (Trial of ORG 10172 in Acute Stroke Treatment) and variables in the ABCD(2) score, only blood pressure >140/90 mm Hg (hazard ratio, 2.75; 1.18 to 6.38; P=0.02) and large artery disease (hazard ratio, 2.21; 1.00 to 4.88; P=0.05) were predictive of 90-day risk. The predictive power of the ABCD(2) score is modest in patients with minor stroke, and neither the Essen Stroke Risk Score nor the Stroke Prognosis Instrument II predicts early recurrence. More reliable early risk prediction after minor stroke is required.


3D models of MBP, a biologically active metabolite of bisphenol A, in human estrogen receptor α and estrogen receptor β.
Bisphenol A [BPA] is a widely dispersed environmental chemical that is of much concern because the BPA monomer is a weak transcriptional activator of human estrogen receptor α [ERα] and ERβ in cell culture. A BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene [MBP], has transcriptional activity at nM concentrations, which is 1000-fold lower than the concentration for estrogenic activity of BPA, suggesting that MBP may be an environmental estrogen. To investigate the structural basis for the activity of MBP at nM concentrations and the lower activity of BPA for human ERα and ERβ, we constructed 3D models of human ERα and ERβ with MBP and BPA for comparison with estradiol in these ERs. These 3D models suggest that MBP, but not BPA, has key contacts with amino acids in human ERα and ERβ that are important in binding of estradiol by these receptors. Metabolism of BPA to MBP increases the spacing between two phenolic rings, resulting in contacts between MBP and ERα and ERβ that mimic those of estradiol with these ERs. Mutagenesis of residues on these ERs that contact the phenolic hydroxyls will provide a test for our 3D models. Other environmental chemicals containing two appropriately spaced phenolic rings and an aliphatic spacer instead of an estrogenic B and C ring also may bind to ERα or ERβ and interfere with normal estrogen physiology. This analysis also may be useful in designing novel chemicals for regulating the actions of human ERα and ERβ.


Chemical Defense Against Diverse Coral-Reef Herbivores.
Five secondary metabolites from tropical marine algae and one related compound from an herbivorous sea-hare (Aplysidae) were coated, at approximately natural concentrations, onto the palatable seagrass Thalassia testudinum and placed on coral reefs where they could be eaten by the diverse group of herbivorous fishes that occur there. Laboratory feeding assays with the herbivorous sea urchin Diadema antillarum were also conducted. When compared to appropriate controls, the following terpenoid compounds significantly reduced the amount of Thalassia eaten by both Diadema and reef fishes: stypotriol, from the brown seaweed Stypopodium zonale; pachydictyol-A, which is produced by several genera of tropical (Dictyota and Dilophus) and warm-temperate (Pachydictyon and Glossophora) brown seaweeds; elatol, from the tropical red alga Laurencia obtusa; and isolaurinterol, which is produced by several tropical and warm-temperate species of Laurencia. Under very mild acid conditions, isolaurinterol is converted to a structurally similar compound, aplysin, found in high concentrations in sea-hares that feed on isolaurinterol-containing Laurencia species. Aplysin did not deter feeding by either type of herbivore. Cymopol, a terpenoid bromohydroquinone from the green alga Cymopolia barbata, significantly reduced feeding by reef fishes but significantly stimulated feeding by Diadema. Pharmacological and crude bioactivity tests suggest that several of these compounds function as generalized toxins. However, these generalized laboratory assays are not necessarily good predictors of how compounds will affect feeding by herbivores. For example, pachydictyol-A and stypotroil were equally effective at deterring fishes and Diadema, even though pachydictyol-A shows almost no bioactivity in laboratory assays while stypotriol and its oxidation product, stypoldione, are very bioactive. Herbivory on coral reefs is more intense than in any other habitat studied and the diversity of herbivore types is high. It appears that this intense grazing has provided strong selection for seaweeds that synthesize unique secondary metabolites that significantly reduce the consumption of plants exposed to attack by a diverse group of reef herbivores.


Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center.
Studies detailing differences in positive surgical margin among open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted laparoscopic radical prostatectomy are lacking. A retrospective review of all prostatectomies with positive surgical margin performed at our center in 2007 disclosed 99 cases, 6 (5%) of which were reinterpreted cases as having negative margins. Ninety-three cases were, therefore, included, corresponding to 37 retropubic radical prostatectomies, 19 laparoscopic radical prostatectomies, and 37 robotic-assisted laparoscopic radical prostatectomies. The relationship of positive surgical margin characteristics to clinicopathologic parameters and biochemical recurrence was assessed. The most commonly found positive surgical margin site was the apex/distal third in all groups (62% retropubic prostatectomies, 79% laparoscopic prostatectomies, 60% robotic-assisted prostatectomies). Total linear length of positive surgical margin sites was significantly correlated with preoperative prostate-specific antigen, preoperative prostate-specific antigen density, pT stage, and tumor volume (P ≤ .001). We found no significant differences among the 3 groups with respect to total linear length, number of foci, laterality, or location of positive surgical margin. The rate of biochemical recurrence was also comparable in the 3 groups. On univariate analyses, biochemical recurrence was significantly associated with preoperative prostate-specific antigen values, preoperative prostate-specific antigen density, Gleason score, number of positive surgical margins, and total linear length of positive surgical margin (P ≤ .02). Only preoperative prostate-specific antigen density and number of positive surgical margin foci were statistically significant (P ≤ .03) independent predictors of biochemical recurrence. We found no significant difference in positive surgical margin characteristics or biochemical recurrence among the 3 radical prostatectomy modalities. Preoperative prostate-specific antigen density and number of positive surgical margin foci were the only independent predictors of biochemical recurrence.


Triangulation method for determining capillary blood flow and physical characteristics of the skin.
A method capable of measuring blood flow at precise depths within the skin is described. The method determines the static and the dynamic properties of light that is backscattered to small areas on the surface of the skin at several contiguous locations along the expected trajectory of laser-light propagation. From observations the method has been shown to be capable of determining physical characteristics that are unique to the different layers of the skin.


Trends in reporting delay in United States central cancer registries.
Timeliness is one of the key indicators of cancer surveillance data quality, as delayed reporting of cases results in an underestimation of the cancer rate in a population. The purpose of this paper is to assess temporal trends in reporting delay by cancer site from 1999-2010. Using data from the Surveillance, Epidemiology, and End Results (SEER) 9 cancer registries and the New York State Cancer Registry, I calculated short-, medium-, and long-term delay for the most common cancer sites for each year and identified the linear trend. Nearly all sites showed a decrease in delay over the period, and many showed a statistically significant decrease. The decrease in delay was more pronounced in the New York State data. These findings reflect long-term improvement in the timeliness of cancer reporting, but there remains room for improvement. Leukemia and myeloma are especially problematic, as these sites are heavily dependent on reporting by private physicians.


Cell Origins of High-Grade Serous Ovarian Cancer.
High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates. Traditionally, the ovarian surface epithelium (OSE) was long believed to be the origin of HGSC. Since the late 1990s, the fallopian tube epithelium has emerged as a potential primary origin of HGSC. Particularly, serous tubal intraepithelial carcinoma (STIC), a noninvasive tumor lesion formed preferentially in the distal fallopian tube epithelium, was proposed as a precursor for HGSC. It was hypothesized that STIC lesions would progress, over time, to malignant and metastatic HGSC, arising from the fallopian tube or after implanting on the ovary or peritoneum. Many clinical studies and several mouse models support the fallopian tube STIC origin of HGSC. Current evidence indicates that STIC may serve as a precursor for HGSC in high-risk women carrying germline BRCA1 or 2 mutations. Yet not all STIC lesions appear to progress to clinical HGSCs, nor would all HGSCs arise from STIC lesions, even in high-risk women. Moreover, the clinical importance of STIC remains less clear in women in the general population, in which 85⁻90% of all HGSCs arise. Recently, increasing attention has been brought to the possibility that many potential precursor or premalignant lesions, though composed of microscopically-and genetically-cancerous cells, do not advance to malignant tumors or lethal malignancies. Hence, rigorous causal evidence would be crucial to establish that STIC is a bona fide premalignant lesion for metastatic HGSC. While not all STICs may transform into malignant tumors, these lesions are clearly associated with increased risk for HGSC. Identification of the molecular characteristics of STICs that predict their malignant potential and clinical behavior would bolster the clinical importance of STIC. Also, as STIC lesions alone cannot account for all HGSCs, other potential cellular origins of HGSC need to be investigated. The fallopian tube stroma in mice, for instance, has been shown to be capable of giving rise to metastatic HGSC, which faithfully recapitulates the clinical behavior and molecular aspect of human HGSC. Elucidating the precise cell(s) of origin of HGSC will be critical for improving the early detection and prevention of ovarian cancer, ultimately reducing ovarian cancer mortality.


Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group.
Hereditary spastic paraplegia (HSP) is a diverse group of inherited disorders characterized by progressive lower-extremity spasticity and weakness. Insight into the genetic basis of these disorders is expanding rapidly. Uncomplicated autosomal dominant, autosomal recessive, and X-linked HSP are genetically heterogeneous: different genes cause clinically indistinguishable disorders. A locus for autosomal recessive HSP is on chromosome 8q. Loci for autosomal dominant HSP have been identified on chromosomes 2p, 14q, and 15q. One locus (Xq22) has been identified for X-linked, uncomplicated HSP and shown to be due to a proteolipoprotein gene mutation in one family. The existence of HSP families for whom these loci are excluded indicates the existence of additional, as yet unidentified HSP loci. There is marked clinical similarity among HSP families linked to each of these loci, suggesting that gene products from HSP loci may participate in a common biochemical cascade, which, if disturbed, results in axonal degeneration that is maximal at the ends of the longest CNS axons. Identifying the single gene defects that cause HSPs distal axonopathy may provide insight into factors responsible for development and maintenance of axonal integrity. We review clinical, genetic, and pathologic features of HSP and present differential diagnosis and diagnostic criteria of this important group of disorders. We discuss polymorphic microsatellite markers useful for genetic linkage analysis and genetic counseling in HSP.


Morphological and physiological differentiation of Purkinje neurons in cultures of rat cerebellum.
During ontogeny, vertebrate CNS neurons differentiate from relatively simple stem cells to complex units that express unique morphological and electrophysiological characteristics. We have examined several aspects of this developmental process in an identified CNS neuronal type, the Purkinje neuron (PN) of the cerebellum. Our approach has included the use of a tissue culture preparation and immunohistochemical and electrophysiological techniques. Using immunohistochemical techniques, we have identified immature PNs in culture and examined their morphological and synaptic development. These studies have shown that PNs undergo extensive morphological and synaptic development in culture, the morphological characteristics of the immature PNs in culture and the developmental sequence and time course are reflective of that described for PNs in vivo, synapse formation is initiated at an early stage of PN development in culture and proceeds concurrently with the morphological development, and the main period of synapse formation is associated with the main period of dendritic development, reflecting the preferential location of synaptic sites at the dendritic region of mature PN. Using electrophysiological techniques, we have examined the physiological development of PNs in culture and have correlated the stages in physiological, morphological, and synaptic development. Results from these studies show the following. Mature PNs in culture exhibit complex electrophysiological properties, including the ability to generate 2 types of spike events, simple and complex spikes, and endogenously generated activity. Expression of electrophysiological properties begins at an early stage in PN development, when the PNs consist of little more than a soma with a few fine perisomatic processes. The earliest physiological characteristics to be expressed by the PN include sensitivity to transmitters, the ability to respond to synaptic input, and the ability to generate simple spikes. Synaptic input produces spontaneous activity in young PNs, but the patterns of activity change during development as mechanisms underlying endogenously generated activity and complex spike generation are expressed, and synapse formation proceeds.(ABSTRACT TRUNCATED AT 400 WORDS)


Function of N-terminal pro-brain natriuretic peptide in Takayasu arteritis disease monitoring.
Increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality. Inflammation may also affect levels of NT-proBNP. We investigated the relationship of NT-proBNP with inflammation, disease activity, disease severity, and progression of Takayasu arteritis (TA). Plasma levels of NT-proBNP were determined in 68 patients with TA and in 90 control subjects. Disease activity and disease severity in patients with TA were defined according to the National Institutes of Health and Ishikawa's criteria, respectively. NT-proBNP levels were higher in patients with active disease (915.0 ± 328.0 pmol/l) and patients in remission (618.2 ± 243.4 pmol/l) than in controls (427.2 ± 81.4 pmol/l) (p < 0.001). Patients with severe TA showed significantly higher NT-proBNP levels than those with mild-moderate TA (924.0 ± 332.4 pmol/l vs 653.8 ± 269.1 pmol/l; p = 0.001). In patients with longitudinal data, NT-proBNP levels at the active phase were significantly higher than those at the stable phase (944.1 ± 216.7 pmol/l vs 552.1 ± 178.2 pmol/l; p = 0.001). Inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, were independently associated with NT-proBNP levels after adjustment for other confounding factors (R(2) adjusted = 0.307, p = 0.001). NT-proBNP levels were significantly increased in patients with active TA exhibiting complications. NT-proBNP levels were independently associated with inflammation. These results indicate that NT-proBNP may be a useful marker to assess the status, severity, and progression of TA.


Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin.
Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.


Ether-linked lysophospholipids initiate insulin secretion. Lysophospholipids may mediate effects of phospholipase A2 activation on hormone release.
Phospholipase A2 activation may be a pivotal step in glucose-induced insulin secretion; however, recent studies have focused on only one by-product (arachidonic acid). To examine the possible role of the other by-product (lysophospholipids), the lysoderivatives of alkylacyl- (ether linked) or diacylphospholipids were applied to rat islets in static incubations. 1-O-alkyl-2-lyso-sn-glyceryl-3-phosphorylcholine [lyso-PAF, the precursor of platelet-activating factor (PAF)] or lysophosphatidylcholine initiated insulin release at 1.7 mM glucose. Two preparations of PAF itself (0.005-5000 ng/ml) were without effect at 1.7 or 16.7 mM glucose, but PAF was nearly equipotent to lyso-PAF at greater than or equal to 20 micrograms/ml. A precursor-product relationship was suggested because the precursors (alkylacyl- or diacylglyceryl-phosphorylcholine) of all three active metabolites were inactive. The stimulatory effect of lyso-PAF is largely independent of any toxic or lytic effect, being biphasic, reversible, unassociated with impairment of the subsequent physiologic functioning of treated islets, and inhibitable (by Ni2+, La3+, or nordihydroguaiaretic acid but not by other lipoxygenase inhibitors). It also occurred at threshold concentrations at which islet morphology and 51Cr retention were preserved. Furthermore, lyso-PAF-induced insulin secretion was markedly impaired by reduced ambient temperature (16 degrees C) or by the impermeant anion isethionate, further implying initiation of true exocytotic granule release and fission. Lyso-PAF (but not arachidonic acid) also circumvented the inhibition of glucose-induced insulin release caused by phospholipase inhibitors. Generation of endogenous lysophospholipids through exogenous application of phospholipase A2 also initiated insulin release, an effect responding to a panel of potential inhibitors identically to that induced by exogenously provided lysophospholipids. We propose that glucose activates phospholipase A2 in the pancreatic islet, leading to the generation of lysophospholipids; the latter may couple energy production to insulin release, at least in part via the promotion of Ca2+ translocation.


CrimAnalyzer: Understanding Crime Patterns in São Paulo.
São Paulo is the largest city in South America, with crime rates that reflect its size. The number and type of crimes vary considerably around the city, assuming different patterns depending on urban and social characteristics of each particular location. Previous works have mostly focused on the analysis of crimes with the intent of uncovering patterns associated to social factors, seasonality, and urban routine activities. Therefore, those studies and tools are more global in the sense that they are not designed to investigate specific regions of the city such as particular neighborhoods, avenues, or public areas. Tools able to explore specific locations of the city are essential for domain experts to accomplish their analysis in a bottom-up fashion, revealing how urban features related to mobility, passersby behavior, and presence of public infrastructures (e.g., terminals of public transportation and schools) can influence the quantity and type of crimes. In this paper, we present CrimAnalyzer, a visual analytic tool that allows users to study the behavior of crimes in specific regions of a city. The system allows users to identify local hotspots and the pattern of crimes associated to them, while still showing how hotspots and corresponding crime patterns change over time. CrimAnalyzer has been developed from the needs of a team of experts in criminology and deals with three major challenges: i) flexibility to explore local regions and understand their crime patterns, ii) identification of spatial crime hotspots that might not be the most prevalent ones in terms of the number of crimes but that are important enough to be investigated, and iii) understand the dynamic of crime patterns over time. The effectiveness and usefulness of the proposed system are demonstrated by qualitative and quantitative comparisons as well as by case studies run by domain experts involving real data. The experiments show the capability of CrimAnalyzer in identifying crime-related phenomena.


Abuse against elderly in India--the role of education.
Abuse against the elderly is recognized as an important challenge to elderly health, but its determinants are not yet well understood. We present findings from a new dataset which covers a representative sample of the population aged 60 years and above from seven Indian states across India - all of which have a higher proportion aged 60 plus compared to the national average. Earlier studies suggest that schooling levels can be relevant in determining the level of abuse against seniors. This study focuses on the role of education on the prevalence of elderly abuse in India. We conduct an analysis of cross sectional primary data that contains information on elderly abuse. The households in the sample were randomly selected from the seven demographically oldest states in India. These states are Himachal Pradesh, Kerala, Maharashtra, Odisha, Punjab, Tamil Nadu and West Bengal. A total of 9852 elderly from 8329 households were interviewed. The statistical analysis is based on logistic regression to understand the independent relation of education with abuse against the elderly. Our findings reveal that 11% of 60+ year olds have experienced at least one type of elderly abuse (Physical 5.3%, Verbal 10.2%, Economic 5.4%, Disrespect 6%, Neglect 5.2%). The most common perpetrator is the son, who is reported to be responsible for the abuse among 41% of male victims and 43% of female victims. Formal education among elderly beyond a certain level (8 years) has a strong relation with reduced violence against elderly. Our findings suggest that level of schooling among elderly is strongly negatively related to abuse against them. More members in the household reduces the chance of abuse while having a greater number of children increases the chance of abuse (neglect and verbal abuse). We find that education even after controlling for wealth and other relevant variables is the factor that most consistently lowers elderly abuse. However, the relation of education to abuse is limited to those with more than 8 years of schooling. This suggests that the ongoing educational expansion beyond the basic schooling years in India may lead to a decline in the incidence of elderly abuse.


Hospital volume and the risk of revision in Oxford unicompartmental knee arthroplasty in the Nordic countries -an observational study of 14,496 cases.
High procedure volume and dedication to unicompartmental knee arthroplasty (UKA) has been suggested to improve revision rates. This study aimed to quantify the annual hospital volume effect on revision risk in Oxfordu nicompartmental knee arthroplasty in the Nordic countries. 14,496 cases of cemented medial Oxford III UKA were identified in 126 hospitals in the four countries included in the Nordic Arthroplasty Register Association (NARA) database from 2000 to 2012. Hospitals were divided by quartiles into 4 annual procedure volume groups (≤11, 12-23, 24-43 and ≥44). The outcome was revision risk after 2 and 10 years calculated using Kaplan Meier method. Multivariate Cox regression analysis was used to assess the Hazard Ratio (HR) of any revision due to specific reasons with 95% confidence intervals (CI). The implant survival was 80% at 10 years in the volume group ≤11 procedures per year compared to 83% in other volume groups. The HR adjusted for age category, sex, year of surgery and nation was 0.87 (95% CI: 0.76-0.99, p = 0.036) for the group 12-23 procedures per year, 0.78 (95% CI: 0.68-0.91, p = 0.002) for the group 24-43 procedures per year and 0.82 (95% CI: 0.70-0.94, p = 0.006) for the group ≥44 procedures per year compared to the low volume group. Log-rank test was p = 0.003. The risk of revision for unexplained pain was 40-50% higher in the low compared with other volume groups. Low volume hospitals performing ≤11 Oxford III UKAs per year were associated with an increased risk of revision compared to higher volume hospitals, and unexplained pain as revision cause was more common in low volume hospitals.


Photo-elastic properties of the wing imaginal disc of Drosophila.
In the study of developmental biology, the physical properties and constraints of the developing tissues are of great importance. In spite of this, not much is known about the elastic properties of biologically relevant tissues that are studied in biology labs. Here, we characterize properties of the wing imaginal disc of Drosophila, which is a precursor organ intensely studied in the framework of growth control and cell polarity. In order to determine the possibility of measuring mechanical stresses inside the tissue during development, we quantify the photo-elastic properties of the tissue by direct mechanical manipulation. We obtain a photo-elastic constant of 2 x 10(-10) Pa(-1).


Feasibility of a RCT of techniques for managing an impacted fetal head during emergency caesarean section: the MIDAS scoping study.
Second-stage caesarean sections, of which there are around 34,000 per year in the UK, have greater maternal and perinatal morbidity than those in the first stage. The fetal head is often deeply impacted in the maternal pelvis, and extraction can be difficult. Numerous techniques are reported, but the superiority of one over another is contentious and there is no national guidance. To determine the feasibility of a randomised trial of different techniques for managing an impacted fetal head during emergency caesarean. A scoping study with five work packages: (1) national surveys to determine current practice and acceptability of research in this area, and a qualitative study to determine acceptability to women who have experienced a second-stage caesarean; (2) a national prospective observational study to determine incidence and rate of complications; (3) a Delphi survey and consensus meeting on choice of techniques and outcomes for a trial; (4) the design of a trial; and (5) a national survey and qualitative study to determine acceptability of the proposed trial. Secondary care. Health-care professionals, pregnant women, women who have had a second-stage caesarean, and parents. Most (244/279, 87%) health-care professionals believe that a trial in this area would help guide their practice, and 90% (252/279) would be willing to participate in such a trial. Thirty-eight per cent (98/259) of parents reported that they would take part. Women varied in which technique they thought was most acceptable. Our observational study found that impacted head is common (occurring in 16% of second-stage caesareans) and leads to both maternal (41%) and neonatal (3.5%) complications. It is most often treated by an assistant pushing the head up vaginally. We designed a randomised clinical trial comparing the fetal pillow with the vaginal push technique. The vast majority of health-care professionals, 83% of midwives and 88% of obstetricians, would be willing to participate in the trial proposed, and 37% of parents reported that they would take part. Our qualitative study found that most participants thought the trial would be feasible and acceptable. Our survey is subject to the limitation that, although responses refer to contemporaneous real cases, they are self-reported by the surgeon and collected after the event. Willingness to participate in a hypothetical trial may not translate into recruitment to a real trial. We proposed a trial to compare a new device, the fetal pillow, with a long-established procedure, the vaginal push technique. Such a trial would be widely supported by health-care professionals. We recommend that it be powered to test an effect on important short term maternal and baby outcomes which would require 754 participants per group. Despite the well-known difference between intent and action, this would be feasible within the UK. We recommend a randomised controlled trial of two techniques for managing an impacted fetal head with an in-built internal pilot phase and alongside economic and qualitative substudies. This study is registered as Research Registry 4942. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 6. See the NIHR Journals Library website for further project information.


Ebola hemorrhagic Fever.
Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers.