Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation.
End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.


Influenza vaccination effectiveness for people aged under 65 years in Japan, 2013/2014 season: application of a doubly robust method to a large-scale, real-world dataset.
Influenza vaccination is recognized as a primary public health intervention which prevents the illness of patients and relieves the societal burdens of influenza for medical community as well as the economy. To date, no effectiveness study of influenza vaccination has been conducted including a large population with a wide age span, in Japan. Here, we evaluated the clinical effectiveness of influenza vaccination in a large Japanese population. We conducted a cohort study using a large-scale claims database for employee health care insurance plans. Vaccination status was identified using plan records for influenza vaccination subsidies. We excluded people aged 65 years or more because of the unavailability of vaccination records. Effectiveness of vaccination in preventing influenza and its complication was evaluated with doubly robust methods using inversed probability treatment weighting to adjust health conscious behaviours and other confounders. During the 2013/2014 influenza season, 369,425 subjects with age range from 1 to 64 years were eligible. Vaccination rate was 39.5% and an estimated odds ratio (OR) for influenza onset was 0.775 after doubly robust adjustment. Age-stratified ORs were significantly reduced in all age groups; lowest in subjects aged 1 to 4 years (0.600) and highest in those aged 13 to 19 (0.938). ORs for all the influenza complication outcomes were also statistically significant (0.403-0.709). We confirmed the clinical effectiveness of influenza vaccination in people aged 1 to 64 years. Influenza vaccination significantly prevented influenza onset and was more effective in reducing secondary risks of influenza complications.


A scoping review of new implementations of interprofessional bedside rounding models to improve teamwork, care, and outcomes in hospitals.
Poor communication within healthcare teams occurs commonly, contributing to inefficiency, medical errors, conflict, and other adverse outcomes. Interprofessional bedside rounds (IBR) are a promising model that brings two or more health professions together with patients and families as part of a consistent, team-based routine to share information and collaboratively arrive at a daily plan of care. The purpose of this systematic scoping review was to investigate the breadth and quality of IBR literature to identify and describe gaps and opportunities for future research. We followed an adapted Arksey and O'Malley Framework and PRISMA scoping review guidelines. PubMed, CINAHL, PsycINFO, and Embase were systematically searched for key IBR words and concepts through June 2020. Seventy-nine articles met inclusion criteria and underwent data abstraction. Study quality was assessed using the Mixed Methods Assessment Tool. Publications in this field have increased since 2014, and the majority of studies reported positive impacts of IBR implementation across an array of team, patient, and care quality/delivery outcomes. Despite the preponderance of positive findings, great heterogeneity, and a reliance on quantitative non-randomized study designs remain in the extant research. A growing number of interventions to improve safety, quality, and care experiences in hospital settings focus on redesigning daily inpatient rounds. Limited information on IBR characteristics and implementation strategies coupled with widespread variation in terminology, study quality, and design create challenges in assessing the effectiveness of models of rounds and optimal implementation strategies. This scoping review highlights the need for additional studies of rounding models, implementation strategies, and outcomes that facilitate comparative research.


Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS.
IFN receptor signaling induces cell-autonomous immunity to infections with intracellular bacterial pathogens. Here, we demonstrate that IFN-inducible guanylate binding protein (Gbp) proteins stimulate caspase-11-dependent, cell-autonomous immunity in response to cytoplasmic LPS. Caspase-11-dependent pyroptosis is triggered in IFN-activated macrophages infected with the Gram-negative bacterial pathogen Legionella pneumophila. The rapid induction of pyroptosis in IFN-activated macrophages required a cluster of IFN-inducible Gbp proteins encoded on mouse chromosome 3 (Gbp(chr3)). Induction of pyroptosis in naive macrophages by infections with the cytosol-invading ΔsdhA L. pneumophila mutant was similarly dependent on Gbp(chr3), suggesting that these Gbp proteins play a role in the detection of bacteria accessing the cytosol. Cytoplasmic LPS derived from Salmonella ssp. or Escherichia coli has recently been shown to trigger caspase-11 activation and pyroptosis, but the cytoplasmic sensor for LPS and components of the caspase-11 inflammasome are not yet defined. We found that the induction of caspase-11-dependent pyroptosis by cytoplasmic L. pneumophila-derived LPS required Gbp(chr3) proteins. Similarly, pyroptosis induced by cytoplasmic LPS isolated from Salmonella was diminished in Gbp(chr3)-deficient macrophages. These data suggest a role for Gbp(chr3) proteins in the detection of cytoplasmic LPS and the activation of the noncanonical inflammasome.


Concurrent visual and motor selection during visual working memory guided action.
Visual working memory enables us to hold onto past sensations in anticipation that these may become relevant for guiding future actions. Yet laboratory tasks have treated visual working memories in isolation from their prospective actions and have focused on the mechanisms of memory retention rather than utilization. To understand how visual memories become used for action, we linked individual memory items to particular actions and independently tracked the neural dynamics of visual and motor selection when memories became used for action. This revealed concurrent visual-motor selection, engaging appropriate visual and motor brain areas at the same time. Thus we show that items in visual working memory can invoke multiple, item-specific, action plans that can be accessed together with the visual representations that guide them, affording fast and precise memory-guided behavior.


Association of inflammatory, lipid and mineral markers with cardiac calcification in older adults.
Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data. We evaluated analytes reflecting lipid (lipoprotein (Lp) (a), Lp-associated phospholipase A2 (LpPLA2) mass and activity), inflammatory (interleukin-6, soluble (s) CD14) and mineral metabolism (fetuin-A, fibroblast growth factor (FGF)-23) pathways that were measured within 5 years of echocardiography. The relationships of plasma biomarkers with aortic valve calcification (AVC), aortic annular calcification (AAC) and mitral annular calcification (MAC) were assessed with relative risk (RR) regression. Calcification was prevalent: AVC 59%, AAC 45% and MAC 41%. After adjustment, Lp(a), LpPLA2 mass and activity and sCD14 were positively associated with AVC. RRs for AVC per SD (95% CI) were as follows: Lp(a), 1.051 (1.022 to 1.081); LpPLA2 mass, 1.036 (1.006 to 1.066) and LpPLA2 activity, 1.037 (1.004 to 1.071); sCD14, 1.039 (1.005 to 1.073). FGF-23 was positively associated with MAC, 1.040 (1.004 to 1.078) and fetuin-A was negatively associated, 0.949 (0.911 to 0.989). No biomarkers were significantly associated with AAC. This study shows novel associations of circulating FGF-23 and fetuin-A with MAC, and LpPLA2 and sCD14 with AVC, confirming that previously reported for Lp(a). Further investigation of Lp and inflammatory pathways may provide added insight into the aetiology of AVC, while study of phosphate regulation may illuminate the pathogenesis of MAC.


Changing patterns of adult (45-74 years) neurological deaths in the major Western world countries 1979-1997.
To compare changes in 'adult' (45-74 years) 'all-cause deaths' (ACDs) with all neurological death categories by age and gender in the 10 major Western countries between the 1970s (1979-1981) and the 1990s (1995-1997). World Health Organization standardized mortality data for age and gender (1979/97) were used to examine changes in adult mortality rates per million based upon ICD-9 categories for ACDs, 'neurological deaths' and the special neurological categories of 'other neurological deaths' (ONDs) and 'mental disorder deaths' (MDDs), which include the dementias. Ratios of ratios were calculated to demonstrate how each individual country's pattern changed over the period by age and gender, resolving the problem of cross-national comparisons. Rates of change across the endpoints and between age groups (45-54, 55-64, 65-74 and 75+ years) were examined using analysis of variance, stepwise regression analysis and cross-tabulation analyses. Meningitis deaths fell substantially, but there was little change in multiple sclerosis or epilepsy deaths. OND rates for the 1990s increased compared with the 1970s rates for males and female, in actual terms and relative to ACDs for almost all countries. Many of the relative rates of increase were substantially higher than 20%. There were significant statistical differences with respect to relative rates of ONDs between the 1970s and the 1990s data, even when the 75+ years age group was excluded. Significant differences were also found between age groups, but only in the 1990s data. MDD rates showed similar trends. Analyses of actual rates of increase in these causes of death showed that males outnumber females in all ages below 74 years. The extent of this difference remained constant across the endpoints. However, in those aged 75 years and over, females outnumbered males at both endpoints, but this disparity widened significantly in the 1990s data. The 1990s data indicate substantial increases compared with the 1970s data for ONDs (especially amongst 65-74 year olds), and rises in MDDs in 55-64 year olds in five countries, including England and Wales and Germany, and in 65-74 year olds in most countries, suggesting earlier onsets of the underlying conditions. Further country-specific research is required to explain the emerging morbidity and mortality.


Effects of beta-carotene and alpha-tocopherol on bleomycin-induced chromosomal damage.
The number of bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes has been proposed as a measure of the sensitivity of an individual to carcinogens. Although "mutagen sensitivity" (clastogenicity) may be a useful biomarker for the identification of individuals at high risk for DNA damage, there is some uncertainty whether the results of this assay can be modified by environmental factors, such as diet. We designed an intervention study to determine whether micronutrient supplementation with beta-carotene and alpha-tocopherol influenced the mutagenicity score among 22 healthy volunteers. This intervention study followed a double-blind, randomized, cross-over design. Chromatid breaks ranged from 0.30 to 2.30 per cell and were uncorrelated with plasma beta-carotene (r = -0.07; P = 0.50) and a-tocopherol (r = -0.01; P = 0.92) levels, after accounting for the time of the measurement. The average number of breaks per cell was similar (P for difference in means = 0.90) among subjects during periods of vitamin supplementation (mean = 0.87 breaks per cell) and placebo (mean = 0.86 breaks per cell), averaged over groups and after adjustment for baseline breaks. Substantial within-person variation may indicate some imprecision in the mutagen sensitivity assessment. Our results suggest that mutagen sensitivity is not affected by plasma levels of beta-carotene or alpha-tocopherol. Although mutagen sensitivity does not appear to be modified by changes in plasma levels of two common antioxidant vitamins, it may be useful for the identification of high-risk individuals for participation in large intervention studies with cancer outcomes.


High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor.
Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3',5'-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 10(5) GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces "molecule noise." Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons.


Environmental enrichment during development decreases intravenous self-administration of methylphenidate at low unit doses in rats.
Despite the efficacy and widespread use of methylphenidate (MPH) as a treatment modality for attention deficit hyperactivity disorder, clinical and preclinical findings indicate that it has abuse potential. Environmental enrichment reduces susceptibility to cocaine and amphetamine self-administration and decreases impulsive behavior, but its effects on MPH self-administration are unknown. The present experiments sought to determine the influence of environmental enrichment on MPH self-administration. Male rats were raised in an enriched condition (EC) or isolated condition (IC). They were trained to self-administer MPH (0.3 mg/kg/infusion) and then exposed to varying doses of MPH on either a fixed-ratio (experiment 1) or a progressive-ratio (experiment 2) schedule of reinforcement. EC rats earned significantly fewer infusions of MPH at low doses (0.03 and 0.056 mg/kg/infusion) compared with IC rats under both schedules; however, no differences were observed at high unit doses (0.1-1.0 mg/kg/infusion). During saline substitution at the end of MPH self-administration, EC rats also responded less for saline compared with IC rats, indicative of more rapid extinction. As with other stimulant drugs with different mechanisms of action, environmental enrichment during development protects against self-administration of MPH at low unit doses but not at high unit doses.


Beer goggles: blood alcohol concentration in relation to attractiveness ratings for unfamiliar opposite sex faces in naturalistic settings.
The popular notion that alcohol intoxication enhances perceptions of the physical attractiveness of the opposite sex has been inconsistently supported. The current study tested intoxicated and non-intoxicated persons of both genders in naturalistic settings after measuring their blood alcohol concentration (BAC) by a breath test. A sample of 80 heterosexual university student social drinkers was recruited at a campus pub and campus parties over a 3-month period to take a survey rating the attractiveness of unfamiliar faces of the opposite gender presented in photographs. Attractiveness ratings were positively correlated with BAC. Analysis of covariance (ANCOVA) was conducted on attractiveness ratings with independent variables of gender and BAC group, with three levels of the latter: non-intoxicated (BAC = 0), moderately intoxicated (BAC .01% - .09%), and highly intoxicated (BAC .10% - .19%). Both intoxicated groups gave significantly higher attractiveness ratings than non-intoxicated controls. The findings confirm the "beer goggles" phenomenon of folk psychology for both genders, although the mechanism remains unclear.


The impact of high density receptor clusters on VEGF signaling.
Vascular endothelial growth factor (VEGF) signaling is involved in the process of blood vessel development and maintenance. Signaling is initiated by binding of the bivalent VEGF ligand to the membrane-bound receptors (VEGFR), which in turn stimulates receptor dimerization. Herein, we discuss experimental evidence that VEGF receptors localize in caveloae and other regions of the plasma membrane, and for other receptors, it has been shown that receptor clustering has an impact on dimerization and thus also on signaling. Overall, receptor clustering is part of a complex ecosystem of interactions and how receptor clustering impacts dimerization is not well understood. To address these questions, we have formulated the simplest possible model. We have postulated the existence of a single high affinity region in the cell membrane, which acts as a transient trap for receptors. We have defined an ODE model by introducing high- and low-density receptor variables and introduce the corresponding reactions from a realistic model of VEGF signal initiation. Finally, we use the model to investigate the relation between the degree of VEGFR concentration, ligand availability, and signaling. In conclusion, our simulation results provide a deeper understanding of the role of receptor clustering in cell signaling.


Vigor in the face of fluctuating rates of reward: an experimental examination.
Two fundamental questions underlie the expression of behavior, namely what to do and how vigorously to do it. The former is the topic of an overwhelming wealth of theoretical and empirical work particularly in the fields of reinforcement learning and decision-making, with various forms of affective prediction error playing key roles. Although vigor concerns motivation, and so is the subject of many empirical studies in diverse fields, it has suffered a dearth of computational models. Recently, Niv et al. [Niv, Y., Daw, N. D., Joel, D., & Dayan, P. Tonic dopamine: Opportunity costs and the control of response vigor. Psychopharmacology (Berlin), 191, 507-520, 2007] suggested that vigor should be controlled by the opportunity cost of time, which is itself determined by the average rate of reward. This coupling of reward rate and vigor can be shown to be optimal under the theory of average return reinforcement learning for a particular class of tasks but may also be a more general, perhaps hard-wired, characteristic of the architecture of control. We, therefore, tested the hypothesis that healthy human participants would adjust their RTs on the basis of the average rate of reward. We measured RTs in an odd-ball discrimination task for rewards whose magnitudes varied slowly but systematically. Linear regression on the subjects' individual RTs using the time varying average rate of reward as the regressor of interest, and including nuisance regressors such as the immediate reward in a round and in the preceding round, showed that a significant fraction of the variance in subjects' RTs could indeed be explained by the rate of experienced reward. This validates one of the key proposals associated with the model, illuminating an apparently mandatory form of coupling that may involve tonic levels of dopamine.


Immunostaining of modified histones defines high-level features of the human metaphase epigenome.
Immunolabeling of metaphase chromosome spreads can map components of the human epigenome at the single cell level. Previously, there has been no systematic attempt to explore the potential of this approach for epigenomic mapping and thereby to complement approaches based on chromatin immunoprecipitation (ChIP) and sequencing technologies. By immunostaining and immunofluorescence microscopy, we have defined the distribution of selected histone modifications across metaphase chromosomes from normal human lymphoblastoid cells and constructed immunostained karyotypes. Histone modifications H3K9ac, H3K27ac and H3K4me3 are all located in the same set of sharply defined immunofluorescent bands, corresponding to 10- to 50-Mb genomic segments. Primary fibroblasts gave broadly the same banding pattern. Bands co-localize with regions relatively rich in genes and CpG islands. Staining intensity usually correlates with gene/CpG island content, but occasional exceptions suggest that other factors, such as transcription or SINE density, also contribute. H3K27me3, a mark associated with gene silencing, defines a set of bands that only occasionally overlap with gene-rich regions. Comparison of metaphase bands with histone modification levels across the interphase genome (ENCODE, ChIP-seq) shows a close correspondence for H3K4me3 and H3K27ac, but major differences for H3K27me3. At metaphase the human genome is packaged as chromatin in which combinations of histone modifications distinguish distinct regions along the euchromatic chromosome arms. These regions reflect the high-level interphase distributions of some histone modifications, and may be involved in heritability of epigenetic states, but we also find evidence for extensive remodeling of the epigenome at mitosis.


Protocol-developing meta-ethnography reporting guidelines (eMERGe).
Designing and implementing high-quality health care services and interventions requires robustly synthesised evidence. Syntheses of qualitative research studies can provide evidence of patients' experiences of health conditions; intervention feasibility, appropriateness and acceptability to patients; and advance understanding of health care issues. The unique, interpretive, theory-based meta-ethnography synthesis approach is suited to conveying patients' views and developing theory to inform service design and delivery. However, meta-ethnography reporting is often poor quality, which discourages trust in, and use of, meta-ethnography findings. Users of evidence syntheses require reports that clearly articulate analytical processes and findings. Tailored research reporting guidelines can raise reporting standards but none exists for meta-ethnography. This study aims to create an evidence-based meta-ethnography reporting guideline articulating the methodological standards and depth of reporting required to improve reporting quality. The mixed-methods design of this National Institute of Health Research-funded study (http://www.stir.ac.uk/emerge/) follows good practice in research reporting guideline development comprising: (1) a methodological systematic review (PROSPERO registration: CRD42015024709) to identify recommendations and guidance in conducting/reporting meta-ethnography; (2) a review and audit of published meta-ethnographies to identify good practice principles and develop standards in conduct/reporting; (3) an online workshop and Delphi studies to agree guideline content with 45 international qualitative synthesis experts and 45 other stakeholders including patients; (4) development and wide dissemination of the guideline and its accompanying detailed explanatory document, a report template for National Institute of Health Research commissioned meta-ethnographies, and training materials on guideline use. Meta-ethnography, devised in the field of education, is now used widely in other disciplines. Methodological advances relevant to meta-ethnography conduct exist. The extent of discipline-specific adaptations of meta-ethnography and the fit of any adaptions with the underpinning philosophy of meta-ethnography require investigation. Well-reported meta-ethnography findings could inform clinical decision-making. A bespoke meta-ethnography reporting guideline is needed to improve reporting quality, but to be effective potential users must know it exists, trust it and use it. Therefore, a rigorous study has been designed to develop and promote a guideline. By raising reporting quality, the guideline will maximise the likelihood that high-quality meta-ethnographies will contribute robust evidence to improve health care and patient outcomes.


EPR and X-ray crystallographic characterization of the product-bound form of the MnII-loaded methionyl aminopeptidase from Pyrococcus furiosus.
Methionine aminopeptidases (MetAPs) are ubiquitous metallohydrolases that remove the N-terminal methionine from nascent polypeptide chains. Although various crystal structures of MetAP in the presence of inhibitors have been solved, the structural aspects of the product-bound step has received little attention. Both perpendicular- and parallel-mode electron paramagnetic resonance (EPR) spectra were recorded for the Mn(II)-loaded forms of the type-I (Escherichia coli) and type-II (Pyrococcus furiosus) MetAPs in the presence of the reaction product l-methionine (L-Met). In general, similar EPR features were observed for both [MnMn(EcMetAP-I)]-L-Met and [MnMn(PfMetAP-II)]-L-Met. The observed perpendicular-mode EPR spectra consisted of a six-line hyperfine pattern at g = 2.03 (A = 8.8 mT) with less intense signals with eleven-line splitting at g = 2.4 and 1.7 (A = 4.4 mT). The former feature results from mononuclear, magnetically isolated Mn(II) ions and this signal are 3-fold more intense in the [MnMn(PfMetAP-II)]-L-Met EPR spectrum than in the [MnMn(EcMetAP-I)]-L-Met spectrum. Inspection of the EPR spectra of both [MnMn(EcMetAP-I)]-L-Met and [MnMn(PfMetAP-II)]-L-Met at 40 K in the parallel mode reveals that the [Mn(EcMetAP-I)]-L-Met spectrum exhibits a well-resolved hyperfine split pattern at g = 7.6 with a hyperfine splitting constant of A = 4.4 mT. These data suggest the presence of a magnetically coupled dinuclear Mn(II) center. On the other hand, a similar feature was not observed for the [MnMn(PfMetAP-II)]-L-Met complex. Therefore, the EPR data suggest that L-Met binds to [MnMn(EcMetAP-I)] differently than [MnMn(PfMetAP-II)]. To confirm these data, the X-ray crystal structure of [MnMn(PfMetAP-II)]-L-Met was solved to 2.3 A resolution. Both Mn1 and Mn2 reside in a distorted trigonal bipyramidal geometry, but the bridging water molecule, observed in the [CoCo(PfMetAP-II)] structure, is absent. Therefore, L-Met binding displaces this water molecule, but the carboxylate oxygen atom of L-Met does not bridge between the two Mn(II) ions. Instead, a single carboxylate oxygen atom of L-Met interacts with only Mn1, while the N-terminal amine nitrogen atom binds to M2. This L-Met binding mode is different from that observed for L-Met binding [CoCo(EcMetAP-I)]. Therefore, the catalytic mechanisms of type-I MetAPs may differ somewhat from type-II enzymes when a dinuclear metalloactive site is present.


Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.
Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.


Vitamin D Supplementation As a Potential therapeutic Mediator in Asthma: Does Dose Really Matter? a Critical Review of the Literature.
Around 400 million people across the globe will suffer from asthma in the next 10 years. Although most asthmatics use asthma medications regularly, they occasionally visit the emergency department for aggressive treatment amidst family anxiousness. Vitamin D (VD) not only regulates the expression of genes associated with calcium homeostasis, but also the genes associated with cancers, autoimmune diseases, and infection. VD has also non-genomic activities e.g. it is a potentially safe and effective novel strategy for decreasing the asthma episodes and controlling exacerbations. Our review assessed the dose, serum level, duration of administration and outcomes of VD in cases of asthmas. Although a body of research evidences the effectiveness of VD supplementation in asthma, other studies showed the insignificant response of VD to asthma either with low dose or low achieved serum VD levels. Nevertheless, recent reviews suggest that manipulating VD status holds promise for primary prevention and treatment of asthma. Future research on the relationship between VD and asthma should consider utilizing adequate doses of VD preparations for sufficient duration (likely to be >12 months) aiming to achieve appropriate level of serum VD (25-hydroxyvitamin D) concentration (likely to be at least >40 ng/mL).


Helical structures in proteins.
We examine a minimal model for helix-forming polymers. The monomer-monomer potential energy is based on the anisotropic potentials seen in proteins and is used in conjunction with a wormlike backbone. We show that the coil-helix transition involves four states. As the temperature is lowered, the first observed state is a coil state, the second a collapsed globular, the third a highly flexible helical state, and the fourth a crystalline helical state. We discuss in detail what effect the potential energy form has on these various states by systematically varying the potential from strongly anisotropic to isotropic. The data demonstrate that the foldability of a helix is strongly related to anisotropic nature of the potential. In the isotropic case, we show that the transition following a globular collapse is not first order as postulated for these systems. In the strongly anisotropic case the globular-helix transition is consistent with cooperative first-order-like behavior.


Radiographically negative, asymptomatic, sentinel lymph node positive cutaneous T-cell lymphoma in a 3-year-old male: a case report.
We present a case of a 3-year-old male originally diagnosed with a CD30+ anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB) was performed as an additional step in the workup and showed microscopic disease. Current management/recommendations for cutaneous T-cell lymphoma do not include SLNB. Medical and surgical management of cutaneous malignancies is dramatically different for local versus advanced disease. Therefore adequate evaluation is necessary to properly stage patients for specific treatment. Such distinction in extent of disease suggests more extensive therapy including locoregional radiation and systemic chemotherapy versus local excision only. Two international case reports have described SLNB in cutaneous T-cell lymphoma with one demonstrating evidence of node positive microscopic disease despite a negative metastatic disease workup. This case is being presented as a novel case in a child with implications including lymphoscintigraphy and SLNB as a routine procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient does not demonstrate evidence of metastatic disease on routine workup.


Pulse compression by use of deformable mirrors.
An electrostatically deformable, gold-coated, silicon nitride membrane mirror was used as a phase modulator to compress pulses from 92 to 15 fs. Both an iterative genetic algorithm and single-step dispersion compensation based on frequency-resolved optical gating calibration of the mirror were used to compress pulses to within 10% of the transform limit. Frequency-resolved optical gating was used to characterize the pulses and to test the range of the deformable-mirror-based compressor.


Numerical investigation of quasi-coplanar plasmonic waveguide-based photonic components.
Using 3-dimensional numerical simulations, we investigated the characteristics and performance of essential photonic components based on the recently proposed quasi-coplanar waveguide (QCPW) including bends, couplers, and splitters. The results confirmed the QCPW's potential in high density photonic integration. We also explored the application of various RF-originated concepts and techniques to QCPW-based photonic components to enhance and enrich their functionalities.


Comparison of Direct and Indirect Methods of Measuring Arterial Blood Pressure in Healthy Male Rhesus Macaques (Macaca mulatta).
Blood pressure is a critical parameter for evaluating cardiovascular health, assessing effects of drugs and procedures, monitoring physiologic status during anesthesia, and making clinical decisions. The placement of an arterial catheter is the most direct and accurate method for measuring blood pressure; however, this approach is invasive and of limited use during brief sedated examinations. The objective of this study was to determine which method of indirect blood pressure monitoring was most accurate compared with measurement by direct arterial catheterization. In addition, we sought to determine the relative accuracy of each indirect method (compared with direct arterial measurement) at a given body location and to assess whether the accuracy of each indirect method was dependent on body location. We compared direct blood pressure measurements by means of catheterization of the saphenous artery with oscillometric and ultrasonic Doppler flow detection measurements at 3 body locations (forearm, distal leg, and tail base) in 16 anesthetized, male rhesus macaques. The results indicate that oscillometry at the forearm is the best indirect method and location for accurately and consistently measuring blood pressure in healthy male rhesus macaques.


Horizontal and vertical dimensions of visual extinction: a theta burst stimulation study.
After a lesion of the posterior parietal cortex (PPC), the perception of a contra-lesional stimulus in presence of a simultaneous, ipsilesional stimulus may be impaired, a phenomenon referred to as visual extinction. In the present study, visual extinction was transiently induced in healthy subjects by interfering with the function of the right PPC by means of continuous theta burst stimulation (TBS). We investigated to which extent the horizontal and vertical position of visual stimuli influenced the extinction rate. A single TBS train over the right PPC induced a significant increase of left visual extinctions of at least 30 min. Left visual extinction rate was higher when the left sided visual stimulus was presented at a more eccentric position on the horizontal axis (irrespective of right sided visual stimulus position) and in the lower part of the visual field. The results are discussed within the framework of current explanatory models and of putative inter- and intrahemispheric mechanisms directing visuospatial attention.


Dynamic ubiquitin signaling in cell cycle regulation.
The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation.


An abnormality in glucocorticoid receptor expression differentiates steroid responders from nonresponders in keloid disease.
Glucocorticoids (GCs) are first-line treatment for keloid disease (KD) but are limited by high incidence of resistance, recurrence and undesirable side-effects. Identifying patient responsiveness early could guide therapy. Nineteen patients with KD were recruited at week 0 (before treatment) and received intralesional steroids. At weeks 0, 2 and 4, noninvasive imaging and biopsies were performed. Responsiveness was determined by clinical response and a significant reduction in vascular perfusion following steroid treatment, using full-field laser perfusion imaging (FLPI). Responsiveness was also evaluated using (i) spectrophotometric intracutaneous analysis to quantify changes in collagen and melanin and (ii) histology to identify changes in epidermal thickness and glycosaminoglycan (GAG) expression. Biopsies were used to quantify changes in glucocorticoid receptor (GR) expression using quantitative reverse transcriptase polymerase chain reaction, immunoblotting and immunohistochemistry. At week 2, the FLPI was used to separate patients into steroid responsive (n = 12) and nonresponsive groups (n = 7). All patients demonstrated a significant decrease in GAG at week 2 (P < 0.05). At week 4, responsive patients exhibited significant reduction in melanin, GAG, epidermal thickness (all P < 0.05) and a continued reduction in perfusion (P < 0.001) compared with nonresponders. Steroid-responsive patients had increased GR expression at baseline and showed autoregulation of GR compared with nonresponders, who showed no change in GR transcription or protein. This is the first demonstration that keloid response to steroids can be measured objectively using noninvasive imaging. FLPI is a potentially reliable tool to stratify KD responsiveness. Altered GR expression may be the mechanism gating therapeutic response.


Emergency Department Overcrowding And The Full Capacity Protocol Cross Over Study: What Patients Who Have Experienced Both Think About Being An Extra Patient In The Emergency Department Or On A Ward.
Hospital overcrowding is evidenced by Emergency Department (ED) overcrowding. The Full Capacity Protocol (FCP) is activated to move patients to temporary extra beds placed in the inpatient wards. This research aims to establish patient preferences when waiting for a ward bed in an Irish Hospital. The FCP in Beaumont Hospital was updated in the context of national guidelines. Patients' attitudes towards boarding in the ED as opposed to being in extra beds on the wards were assessed using a questionnaire based structured interview. Ninety nine patients took part in the study. Eighty three patients (83.83%) preferred being an additional patient on the ward, 12 (12.12%) had no preference and four (4.04%) preferred being boarded in the ED. Moving patients from the ED into extra beds on the wards creates space, facilitating safer care delivery. The vast majority of patients who have experienced both, prefer being boarded in the ward rather than in the ED.


Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.
Recessive ryanodine receptor 1 (RYR1) mutations cause congenital myopathies including multiminicore disease (MmD), congenital fiber-type disproportion and centronuclear myopathy. We created a mouse model knocked-in for the Q1970fsX16+A4329D RYR1 mutations, which are isogenic with those identified in a severely affected child with MmD. During the first 20 weeks after birth the body weight and the spontaneous running distance of the mutant mice were 20% and 50% lower compared to wild-type littermates. Skeletal muscles from mutant mice contained 'cores' characterized by severe myofibrillar disorganization associated with misplacement of mitochondria. Furthermore, their muscles developed less force and had smaller electrically evoked calcium transients. Mutant RyR1 channels incorporated into lipid bilayers were less sensitive to calcium and caffeine, but no change in single-channel conductance was observed. Our results demonstrate that the phenotype of the RyR1Q1970fsX16+A4329D compound heterozygous mice recapitulates the clinical picture of multiminicore patients and provide evidence of the molecular mechanisms responsible for skeletal muscle defects.


Incorporating patient perspectives into the personal health record: implications for care and caring.
Electronic personal health records (ePHRs) can potentially maximize access and coordination of health information and improve patient/clinician collaboration, patient self-management, and health outcomes. Most ePHRs are designed by vendors, physicians, and other proprietary partners and have neglected the patient perspective. This study sought to incorporate patient feedback into an existing ePHR system. Patients participated in a semistructured interview after one to two weeks of using an ePHR. Interviews addressed strengths and weaknesses of the PHR. Two iterations of interviews, referred to as Wave 1 and Wave 2, occurred sequentially. An iterative process of theme identification was used, and three theme categories (User, System Acceptance, and Technology) were identified in the two waves. Seven technology themes with 40 specific questions were identified and were rank ordered by importance and feasibility, and 20 suggestions were subsequently implemented into the ePHR. Thus, incorporating patient feedback on specific utilities and functionality into an existing ePHR is possible.


The impact of labor-saving technology on first birth intervals in rural Ethiopia.
Across the developing world labor-saving technologies introduce considerable savings in the time and energy that women allocate to work. Hormonal studies on natural fertility populations indicate that such a reduction in energetic expenditure (rather than improved nutritional status alone) can lead to increased ovarian function. Other qualitative studies have highlighted a link between labor-saving technology and behavioral changes affecting subsequent age at marriage, which may affect fertility. This biodemographic study was designed to investigate whether these physiological and behavioral changes affect fertility at a population level by focusing on a recent water development scheme in Southern Ethiopia. The demographic consequences of a reduction in women's workload following the installation of water points, specifically the variation in length of first birth interval (time lapsed between marriage and first birth), are investigated. First birth interval length is closely associated with lifetime fertility in populations that do not practice contraception, longer intervals being associated with lower fertility. Using life tables and multivariate hazard modeling techniques a number of significant predictors of first birth interval length are identified. Covariates such as age at marriage, season of marriage, village ecology, and access to improved water supply have significant effects on variation in first birth intervals. When entered into models as a time-varying covariate, access to a water tap stand is associated with an immediate reduction in length of first birth intervals.


Can the 12-item General Health Questionnaire be used to measure positive mental health?
Well-being is an important determinant of health and social outcomes. Measures of positive mental health states are needed for population-based research. The 12-item General Health Questionnaire (GHQ-12) has been widely used in many settings and languages, and includes positively and negatively worded items. Our aim was to test the hypothesis that the GHQ-12 assesses both positive and negative mental health and that these domains are independent of one another. Exploratory (EFA) and confirmatory (CFA) factor analyses were conducted using data from the British Household Panel Survey (BHPS) and the Health Survey for England (HSE). Regression models were used to assess whether associations with individual and household characteristics varied across positive and negative mental health dimensions. We also explored higher-level variance in these measures, between electoral wards. We found a consistent, replicable factor structure in both datasets. EFA results indicated a two-factor solution, and CFA demonstrated that this was superior to a one-factor model. These factors correspond to 'symptoms of mental disorder' and 'positive mental health'. Further analyses demonstrated independence of these factors in associations with age, gender, employment status, poor housing and household composition. Statistically significant ward-level variance was found for symptoms of mental disorder but not positive mental health. The GHQ-12 measures both positive and negative aspects of mental health, and although correlated, these dimensions have some independence. The GHQ-12 could be used to measure positive mental health in population-based research.


Wear resistance of cryogenically treated stainless steel files.
Cryogenic treatment, which involves ultra-sub-zero treatment of metal alloys, has been shown to improve the wear resistance of several types of stainless steel. The purpose of this study was to examine the effect of cryogenic treatment on wear resistance of Flex-R and Hedstrom (Union Broach) files. These instruments were attached to an Instron testing machine and underwent 300 push-pull strokes (6-mm movement range, 600-mm/min speed, 1-N loading) against 1.5-mm thick dentin wafers. Their wear was determined by comparing the depth of grooves (without changing file position) cut in acrylic specimens (1.5-mm thick) before and after machining dentin. The mean and standard deviation (n = 20) of the relative change in cutting efficiency was determined for the files. An analysis of variance showed that the cutting efficiency of all files decreased significantly after wearing on dentin (p < 0.0001). However, when comparing the post-/pre-cutting efficiency ratios of the files, it was seen that cryogenic treatment did not affect the wear resistance of the files.


Why do patients turn to complementary medicine? An empirical study.
Over 250 patients from three complementary medicine practices-acupuncture, osteopathy and homoeopathy-completed a questionnaire rating 20 potential reasons for seeking complementary treatment. The reasons that were most strongly endorsed were "because I value the emphasis on treating the whole person'; "because I believe complementary therapy will be more effective for my problem than orthodox medicine'; "because I believe that complementary medicine will enable me to take a more active part in maintaining my health'; and "because orthodox treatment was not effective for my particular problem'. Five factors were identified, in order of importance: a positive valuation of complementary treatment, the ineffectiveness of orthodox treatment for their complaint, concern about the adverse effects of orthodox medicine, concerns about communication with doctors and, of less importance, the availability of complementary medicine. Groups were compared, using analysis of covariance to control for demographic differences between the three patient groups. Osteopathy patients' reasons indicated they were least concerned about the side effects of orthodox medicine and most influenced by the availability of osteopathy for their complaints. Homoeopathy patients were most strongly influenced by the ineffectiveness of orthodox medicine for their complaints, a fact which was largely accounted for by the chronicity of their complaints. Results are discussed in terms of the limited research in this area. Future studies should separate the reasons for beginning complementary treatment from the reasons for continuing it. It is possible, for instance, that the failure of orthodox medicine is the strongest motive for seeking complementary treatment but that, once treatment has been experienced, other more positive factors become more important.


Health status and the housing system.
Most research on housing and health seeks causal links between dwelling conditions and the incidence of physical and mental disease. Less attention has been paid to the more sociological question of how health status affects housing opportunities. This paper shows how, and considers why, medical factors influence access to housing, whether in the public sector (where accommodation is traditionally allocated according to 'need') or in the housing market (where dwelling availability depends on ability to pay). In Britain, whose experience is taken as an example, a shrinking council housing stock can no longer accommodate general medical needs. Consequently, notwithstanding the importance of 'special' housing initiatives, many sick people are forced to seek accommodation in the private sector. Whether they succeed or fail (and so become homeless), this raises questions concerning the health selective role of the housing system which analysts have scarcely begun to address.


Usefulness of an individualized balance and gait intervention programme based on the problem-oriented assessment of mobility in nursing home residents.
To examine the usefulness of an individualized balance and gait training proramme according to the specific problems identified from the problem-oriented assessment of mobility (POAM) in residents of a nursing home. The clinical records of 74 NH residents (49 female, 25 male) who were consecutively referred to physical therapy for problems related to poor balance or gait or a recent fall in a 2 year period were reviewed retrospectively for the study. According to the medical charts, patients had received a four week (20 sessions) problem-oriented exercise programme that specifically targeted balance and gait deficits identified from the POAM and the retest had been done after four weeks of training. The mean initial and final balance scores were 8.47+/-3.80. and 10.77+ /-3.37. respectively, and the mean gait scores were 6.73+/-2.30 initially and 7.71+/-1.95 finally. A Wilcoxon signed-rank comparison of the initial and final POAM indicated that significant improvement occurred in the balance scores (Z = 5.345, p < 0.0001) and the gait scale (Z = 3.589, p < 0.0001) in this group. Item analysis demonstrated the number of patients who improved or did not change on individual items. Both balance and gait were significantly improved after a four-week intervention programme based on the deficits identified by POAM. The POAM is a useful tool to guide the clinician to target specific balance and gait deficits for individual nursing home elders.


Diagnosing Large Vestibular Aqueduct: Radiological Review of High-Resolution CT Versus High-Resolution Volumetric MRI.
To compare the diagnostic yield of high-resolution volumetric T2-weighted MRI (HRT2-MRI) with high-resolution computed tomography (HRCT) for diagnosis of large vestibular aqueduct (LVA). Three board-certified neuroradiologists performed an independent, blinded radiological review for diagnosing LVA with 2:1 age-matched controls on patients with both HRCT and HRT2-MRI imaging. Tertiary referral center. All patients between 2002 and 2016 with hearing loss who underwent both HRCT and HRT2-MRI and were diagnosed with LVA on either modality. Concordance rate for LVA between HRCT and HRT2-MRI. Concordance rate for HRCT and HRT2-MRI for diagnosing LVA was 88% (124/141) when assessing both the midpoint and external aperture diameters. Fifteen ears had LVA on computed tomography (CT), but not on magnetic resonance imaging (MRI); in comparison, two ears had LVA on MRI, but not on CT (p = 0.002). Excellent inter-rater reliability among the three radiologists was demonstrated. Historically, HRCT has been the imaging modality of choice for diagnosing LVA. Although a higher concordance rate of HRT2-MRI was found compared with previous studies utilizing earlier MRI technology, HRCT still detected a larger number of patients with clinically significant hearing loss compared with MRI. Given the high concordance rate and efficacy of both modalities in diagnosing LVA, the ultimate decision of which modality to choose may depend on other patient-specific and clinical factors.


Validity of identification of gonion and antegonion in frontal cephalograms.
This study was designed to develop a method of transferring gonion from lateral to frontal cephalograms, and to use this method as gold standard when evaluating observer performance in identifying gonion in frontal cephalograms. Observer ability to identify antegonion was also evaluated. There was a range of 28 mm in the observers' identification of gonion and a statistically significant deviation from gold standard. The factors "observer" and "cephalogram," regarded as random effects in an ANOVA analysis, and their interaction, each influenced the result, P < .001. The deviation from the mean of all observations for antegonion ranged 8 mm with "cephalogram" having a statistically significant influence. The results suggest that neither gonion nor antegonion can be routinely used as valid landmarks in frontal cephalograms. Gonion can, however, be used if first identified in a lateral cephalogram and transferred to a paired frontal cephalogram aided by radiographic indicators combined with a bilateral scrutiny of projection geometry in different planes through gonion and indicator.


Schizophrenia is a cognitive illness: time for a change in focus.
Schizophrenia is currently classified as a psychotic disorder. This article posits that this emphasis on psychosis is a conceptual fallacy that has greatly contributed to the lack of progress in our understanding of this illness and hence has hampered the development of adequate treatments. Not only have cognitive and intellectual underperformance consistently been shown to be risk factors for schizophrenia, several studies have found that a decline in cognitive functioning precedes the onset of psychosis by almost a decade. Although the question of whether cognitive function continues to decline after psychosis onset is still debated, it is clear that cognitive function in schizophrenia is related to outcome and little influenced by antipsychotic treatment. Thus, our focus on defining (and preventing) the disorder on the basis of psychotic symptoms may be too narrow. Not only should cognition be recognized as the core component of the disorder, our diagnostic efforts should emphasize the changes in cognitive function that occur earlier in development. Putting the focus back on cognition may facilitate finding treatments for the illness before psychosis ever emerges.


Sufentanil infusion before extubation suppresses coughing on emergence without delaying extubation time and reduces postoperative analgesic requirement without increasing nausea and vomiting after desflurane anesthesia.
Coughing, hypertension, tachycardia, and even laryngospasm can occur due to airway irritation during emergence from anesthesia. We investigated the effect of maintaining a sufentanil infusion during emergence from anesthesia by evaluating the incidence of cough and recovery profiles at extubation. In total, eighty-four patients undergoing an elective laparoscopic hysterectomy were randomly divided into two sufentanil groups and a control group. During emergence, sufentanil was administered in the sufentanil groups at a rate of 0.2 µg/kg/hr (Group S1) or 0.3 µg/kg/hr (Group S2), and saline was administered to the control group. Cough score, hemodynamic changes, and recovery profiles, such as duration from skin closure to a bispectral index of 80, to eye opening at verbal command, to tracheal extubation and the total duration of study solution infusion, were recorded. The pain score, the total volume of administered patient-controlled analgesia (PCA), and the postoperative nausea and vomiting (PONV) score were evaluated 1, 6, and 24 hours after surgery. Groups S1 and S2 showed significantly lower cough scores and smaller hemodynamic changes on extubation compared to Group C. Recovery profiles showed no significant differences among the three groups. Pain score, PONV at 1 hour postoperatively, and the total volume of PCA administered at all evaluation times were significantly lower in Groups S1 and S2 than in the control group. However, pain score, and PONV at 6 hours and 24 hours postoperatively showed no significant differences. A sufentanil infusion (0.2-0.3 µg/kg/hr) during emergence from desflurane anesthesia may suppress coughing on extubation in patients with body mass indexes (BMI) of 21-26 without delaying extubation time. It may also reduce the postoperative analgesic requirement without increasing PONV.


Hypoglycaemia and antimalarial drugs: quinidine and release of insulin.
Life threatening hypoglycaemia has been closely associated with the use of quinine, but the effect of quinidine and the synthetic antimalarials on the homoeostasis of glucose has not been investigated. In volunteers given a fixed dose of 500 mg base and patients with malaria given a quinidine loading dose (15 mg base/kg) mean (SEM) plasma insulin concentrations rose from 6.1 (1.5) mU/l to 10.9 (4.4) mU/l (p less than 0.02) and 10.4 (2.0) mU/l to 18.5 (5.3) mU/l (p less than 0.04), respectively. Plasma glucose concentrations fell from 4.5 (1.1) mmol/l (81 (20) mg/100 ml) to 4.0 (0.3) mmol/l (72 (5) mg/100 ml) in volunteers (p less than 0.04) and from 5.7 (1.3) mmol/l (102 (23) mg/100 ml) to 4.8 (1.6) mmol/l (86 (29) mg/100 ml) in patients (p less than 0.05). One of two patients with cerebral malaria and acute renal failure became profoundly hypoglycaemic (plasma glucose concentration 1.4 mmol/l (25 mg/100 ml), plasma insulin concentration 3.1 mU/l). Hypoglycaemia may occur in any severely ill fasting patient given parenteral quinidine. The other antimalarials tested, chloroquine, amodiaquine, mefloquine, and halofantrine, did not stimulate the release of insulin, an important advantage that should be taken into account when treatment is chosen for Plasmodium falciparum malaria.


Highly homogeneous antibody modification through optimisation of the synthesis and conjugation of functionalised dibromopyridazinediones.
Due to their exquisite cysteine-selectivity, excellent stability, and ability to functionally rebridge disulfide bonds, dibromopyridazinediones are emerging as an exciting new class of bioconjugation reagents, particularly in the field of antibody conjugation. Despite this, relatively little work has been performed on the optimisation of their synthesis and subsequent reaction with immunoglobulins. Herein we present a novel synthetic route towards functionalised dibromopyridazinediones, proceeding via an isolatable dibromopyridazinedione-NHS ester. Reaction of this activated intermediate with a variety of amines produces functional dibromopyridazinediones in good to excellent yields. The disulfide rebridging capacity of these reagents was optimised on the clinically relevant IgG1 trastuzumab, resulting in a general method which allows for the generation of site-selectively modified native trastuzumab with over 90% homogeneity (no disulfide scrambling) without the need for protein engineering or enzymatic conjugation.


There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy.
In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively. Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108 patients and revealed a complete response in 1 patient of each Rx arm, a partial response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm 2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm 2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The pattern of failure was local in all patients. Morbidity of treatment was similar in both Rx arms, with no significant toxicity (including hearing loss) reported. Autopsy was performed in 6 patients, and confirmed the presence of extensive residual tumor in these cases. The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.


Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout.
Radioiodines, particularly 131I, may be released into the environment in breach-of-containment nuclear reactor accidents and localize in and irradiate the thyroid with an attendant risk of neoplastic growth and other adverse health effects. Pharmacologic thyroid blockade by oral potassium iodide (KI) (50-100 mg in adults) can substantially reduce thyroid uptake of and irradiation by internalized radioiodine. In the current analysis, computer modeling of iodine metabolism has been used to systematically elucidate the effects of two practically important but highly variable factors on the radioprotective effect of KI: the time of administration relative to exposure to radioiodine and the dietary level of iodine. In euthyroid adults receiving iodine-sufficient diets (250 microg d(-1) in the current analysis), KI administered up to 48 h before 131I exposure can almost completely block thyroid uptake and therefore greatly reduce the thyroid absorbed dose. However, KI administration 96 h or more before 131I exposure has no significant protective effect. In contrast, KI administration after exposure to radioiodine induces a smaller and rapidly decreasing blockade effect. KI administration 16 h or later after 131I exposure will have little effect on thyroid uptake and absorbed dose and therefore little or no protective effect. The 131I thyroid absorbed dose is two-fold greater with insufficient levels of dietary iodine, 2,900 cGy/37 MBq, than with sufficient levels of dietary iodine, 1,500 cGy/37 MBq. When KI is administered 48 h or less before 131I intake, the thyroid absorbed doses (in cGy/37 MBq) are comparably low with both sufficient and insufficient dietary iodine levels. When KI is administered after 131I intake, however, the protective effect of KI is less and decreases more rapidly with insufficient than with sufficient dietary iodine. For example, KI administration 2 and 8 h after 131I intake yields protective effects of 80 and 40%, respectively, with iodine-sufficient diets, but only 65 and 15% with iodine-deficient diets. In conclusion, whether exposed populations receive sufficient or insufficient dietary iodine, oral KI is an effective means of reducing thyroid irradiation from environmentally dispersed radioiodine but is effective only when administered within 2 d before to approximately 8 h after radioiodine intake.


Transgenic expression of oncogenic BRAF induces loss of stem cells in the mouse intestine, which is antagonized by β-catenin activity.
Colon cancer cells frequently carry mutations that activate the β-catenin and mitogen-activated protein kinase (MAPK) signaling cascades. Yet how oncogenic alterations interact to control cellular hierarchies during tumor initiation and progression is largely unknown. We found that oncogenic BRAF modulates gene expression associated with cell differentiation in colon cancer cells. We therefore engineered a mouse with an inducible oncogenic BRAF transgene, and analyzed BRAF effects on cellular hierarchies in the intestinal epithelium in vivo and in primary organotypic culture. We demonstrate that transgenic expression of oncogenic BRAF in the mouse strongly activated MAPK signal transduction, resulted in the rapid development of generalized serrated dysplasia, but unexpectedly also induced depletion of the intestinal stem cell (ISC) pool. Histological and gene expression analyses indicate that ISCs collectively converted to short-lived progenitor cells after BRAF activation. As Wnt/β-catenin signals encourage ISC identity, we asked whether β-catenin activity could counteract oncogenic BRAF. Indeed, we found that intestinal organoids could be partially protected from deleterious oncogenic BRAF effects by Wnt3a or by small-molecule inhibition of GSK3β. Similarly, transgenic expression of stabilized β-catenin in addition to oncogenic BRAF partially prevented loss of stem cells in the mouse intestine. We also used BRAF(V637E) knock-in mice to follow changes in the stem cell pool during serrated tumor progression and found ISC marker expression reduced in serrated hyperplasia forming after BRAF activation, but intensified in progressive dysplastic foci characterized by additional mutations that activate the Wnt/β-catenin pathway. Our study suggests that oncogenic alterations activating the MAPK and Wnt/β-catenin pathways must be consecutively and coordinately selected to assure stem cell maintenance during colon cancer initiation and progression. Notably, loss of stem cell identity upon induction of BRAF/MAPK activity may represent a novel fail-safe mechanism protecting intestinal tissue from oncogene activation.


Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity.
The centrosome plays an important role in maintenance of cell polarity and in progression through the cell cycle by determining the number, polarity, and organization of interphase and mitotic microtubules. By examining a set of 35 high grade human breast tumors, we show that centrosomes of adenocarcinoma cells generally display abnormal structure, aberrant protein phosphorylation, and increased microtubule nucleating capacity in comparison to centrosomes of normal breast epithelial and stromal tissues. These structural and functional centrosome defects have important implications for understanding the mechanisms by which genomic instability and loss of cell polarity develop in solid tumors.


Efficacy and safety of filgotinib in Japanese patients with refractory rheumatoid arthritis: Subgroup analyses of a global phase 3 study (FINCH 2).
To evaluate efficacy and safety of filgotinib in Japanese RA patients who have failed or were intolerant to one or more biologic disease-modifying antirheumatic drugs (bDMARD) from the global FINCH 2 study (NCT02873936). This subgroup analysis was performed using the predefined statistical analyses. The FINCH 2 study is a randomized, double-blind, placebo-controlled, Phase 3 study in adult RA patients with inadequate response to bDMARDs. The randomized patients were treated with once-daily filgotinib 200 mg, filgotinib 100 mg or placebo on a background of csDMARDs for 24 weeks. Of 449 patients enrolled in the overall population, 40 patients were enrolled from Japan. In the Japanese population, the American College of Rheumatology 20% response rates at week 12 (primary endpoint) were 83.3% and 53.3% for filgotinib, 200 mg and 100 mg, respectively, vs 30.8% for placebo. Filgotinib was well tolerated, similar to the overall population. Both doses of once-daily filgotinib 200 mg and filgotinib 100 mg were effective, and generally well-tolerated in Japanese patients with active refractory RA.


Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGluR at excitatory synapses.
The nanoscale co-organization of neurotransmitter receptors facing presynaptic release sites is a fundamental determinant of their coactivation and of synaptic physiology. At excitatory synapses, how endogenous AMPARs, NMDARs, and mGluRs are co-organized inside the synapse and their respective activation during glutamate release are still unclear. Combining single-molecule superresolution microscopy, electrophysiology, and modeling, we determined the average quantity of each glutamate receptor type, their nanoscale organization, and their respective activation. We observed that NMDARs form a unique cluster mainly at the center of the PSD, while AMPARs segregate in clusters surrounding the NMDARs. mGluR5 presents a different organization and is homogenously dispersed at the synaptic surface. From these results, we build a model predicting the synaptic transmission properties of a unitary synapse, allowing better understanding of synaptic physiology.


Infection of the germ line by retroviral particles produced in the follicle cells: a possible mechanism for the mobilization of the gypsy retroelement of Drosophila.
The gypsy retroelement of Drosophila moves at high frequency in the germ line of the progeny of females carrying a mutation in the flamenco (flam) gene. This high rate of de novo insertion correlates with elevated accumulation of full-length gypsy RNA in the ovaries of these females, as well as the presence of an env-specific RNA. We have prepared monoclonal antibodies against the gypsy Pol and Env products and found that these proteins are expressed in the ovaries of flam females and processed in the manner characteristic of vertebrate retroviruses. The Pol proteins are expressed in both follicle and nurse cells, but they do not accumulate at detectable levels in the oocyte. The Env proteins are expressed exclusively in the follicle cells starting at stage 9 of oogenesis, where they accumulate in the secretory apparatus of the endoplasmic reticulum. They then migrate to the inner side of the cytoplasmic membrane where they assemble into viral particles. These particles can be observed in the perivitelline space starting at stage 10 by immunoelectron microscopy using anti-Env antibodies. We propose a model to explain flamenco-mediated induction of gypsy mobilization that involves the synthesis of gypsy viral particles in the follicle cells, from where they leave and infect the oocyte, thus explaining gypsy insertion into the germ line of the subsequent generation.


The Incidence of Cisplatin-induced Hypomagnesemia in Cervical Cancer Patients Receiving Cisplatin Alone.
Hypomagnesemia is one side effect in patients receiving cisplatin. However, there are few reports of cisplatin-induced hypomagnesemia in Japan. We retrospectively investigated the incidence of hypomagnesemia and nephrotoxicity in patients undergoing radiation therapy who were treated with cisplatin alone (dosage: 40 mg/m2, administration interval: 1 week) for cervical cancer. Thirty-two patients undergoing radiation therapy who received cisplatin alone for cervical cancer between January 2012 and May 2016 at Aichi Medical University Hospital were included. We measured patients' serum magnesium and creatinine levels on the day before cisplatin was administered. We utilized the RIFLE criteria (categorized into "risk", "injury", "failure", "loss", and "end-stage kidney disease") to define levels of cisplatin-induced nephrotoxicity, and classified cisplatin-induced nephrotoxicity into "risk" or "injury". Eighteen patients (56.3%) had cisplatin-induced hypomagnesemia, the majority of which occurred after the 4th treatment cycle. The number of patients with moderate renal dysfunction classified as "risk" in the hypomagnesemia group was not significantly higher than in the non-hypomagnesemia group (hypomagnesemia group=27.8%, non-hypomagnesemia group=7.1%; p=0.20). This survey sheds light on the incidence rates of cisplatin-induced hypomagnesemia in patients receiving cisplatin alone. We recommend monitoring the serum magnesium levels during cisplatin administration to prevent hypomagnesemia.


Transferable tetracycline resistance in Clostridium perfringens strains of porcine origin.
These studies represent the first systematic survey of the incidence of conjugative antibiotic resistance in Clostridium perfringens. Ninety-two antibiotic-resistant porcine strains were examined to see if they could donate their antibiotic-resistance determinants to sensitive recipient strains. Fifteen of the 89 tetracycline-resistant strains transferred their tetracycline resistance in mixed-plate mating experiments but no transfer of macrolide-lincosamide resistance was detected. The efficiencies of transfer of tetracycline resistance varied from 1.3 X 10(-3) to 1.9 X 10(-6) transconjugants per donor cell. Significantly higher transfer efficiencies were observed when both the donor and recipient strains were derivatives of strain CW 362. These values ranged from 3.7 X 10(-1) to 4.6 X 10(-2) transconjugants per donor cell. This high frequency transfer system should prove invaluable for further genetic studies on this microorganism.


Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide receptor chimeras reveal domains that determine specificity of vasoactive intestinal polypeptide binding and activation.
Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are closely related G protein-coupled receptors with seven-transmembrane domains. The VIP receptor can bind both VIP and PACAP with high affinity, whereas the PACAP receptor binds only PACAP with high affinity. To elucidate the structural domains involved in a selectivity for VIP binding and the subsequent receptor activation, a series of chimeric receptors between the VIP and PACAP receptors was constructed, expressed in COS-7 cells, and analyzed for ligand binding and cAMP generation. All chimeric constructs bound PACAP with high affinity and subsequently activated cAMP generation similarly to the wild-type receptors. In contrast, profound differences were observed in the potencies of VIP for competition of 125I-labeled PACAP binding to both wild-type receptors and the chimeric receptors. The cAMP responses of these receptors generally correlated with the ability of VIP to compete for PACAP radioligand binding with the exceptions for some particular chimeras. In this report we demonstrate that several domains, including the amino-terminal extracellular domain, the transmembrane domains I and II, and the first extracellular loop of the VIP receptor, are important for the selectivity for VIP binding and responsiveness to VIP. We further show that the third extracellular loop and its proximal domains of the VIP receptor appear to be involved in the VIP recognition, especially the receptor activation process. On the other hand, the direct binding experiments of the VIP radioligand demonstrated that both wild-type receptors and all chimeric receptors have a high affinity binding site for VIP, although this high affinity VIP binding resulted in a biological response only in the VIP receptor or VIP receptor-like chimeras. This suggests that there is a nonbiologically relevant high affinity VIP-binding site within the rat PACAP receptor.


Highly Oriented Atomically Thin Ambipolar MoSe2 Grown by Molecular Beam Epitaxy.
Transition metal dichalcogenides (TMDCs), together with other two-dimensional (2D) materials, have attracted great interest due to the unique optical and electrical properties of atomically thin layers. In order to fulfill their potential, developing large-area growth and understanding the properties of TMDCs have become crucial. Here, we have used molecular beam epitaxy (MBE) to grow atomically thin MoSe2 on GaAs(111)B. No intermediate compounds were detected at the interface of as-grown films. Careful optimization of the growth temperature can result in the growth of highly aligned films with only two possible crystalline orientations due to broken inversion symmetry. As-grown films can be transferred onto insulating substrates, allowing their optical and electrical properties to be probed. By using polymer electrolyte gating, we have achieved ambipolar transport in MBE-grown MoSe2. The temperature-dependent transport characteristics can be explained by the 2D variable-range hopping (2D-VRH) model, indicating that the transport is strongly limited by the disorder in the film.


Factors influencing consumption of nutrient rich forest foods in rural Cameroon.
Studies show that a number of forest foods consumed in Cameroon are highly nutritious and rich in health boosting bioactive compounds. This study assessed the knowledge and perceptions towards the nutritional and health promoting properties of forest foods among forest dependent communities. The relationship between knowledge, perceptions and socio-demographic attributes on consumption of forest foods was also determined. A total of 279 females in charge of decision making with respect to food preparation were randomly selected from 12 villages in southern and eastern Cameroon and interviewed using researcher administered questionnaires. Multivariate logistic regression analysis was used to identify the factors affecting consumption of forest foods. Baillonella toxisperma (98%) and Irvingia gabonesis (81%) were the most known nutrient rich forest foods by the respondents. About 31% of the respondents were aware of the nutritional value and health benefits of forest foods. About 10%-61% of the respondents expressed positive attitudes to questions related with health benefits of specific forest foods. Consumption of forest foods was found to be higher among polygamous families and also positively related to length of stay in the forest area and age of respondent with consumption of forest foods. Education had an inverse relationship with use of forest foods. Knowledge and positive attitude towards the nutritional value of forest foods were also found to positively influence consumption of forest foods. Since knowledge was found to influence attitude and consumption, there is need to invest in awareness campaigns to strengthen the current knowledge levels among the study population. This should positively influence the attitudes and perceptions towards increased consumption of forest foods.


Glyconanomaterials for biosensing applications.
Nanomaterials constitute a class of structures that have unique physiochemical properties and are excellent scaffolds for presenting carbohydrates, important biomolecules that mediate a wide variety of important biological events. The fabrication of carbohydrate-presenting nanomaterials, glyconanomaterials, is of high interest and utility, combining the features of nanoscale objects with biomolecular recognition. The structures can also produce strong multivalent effects, where the nanomaterial scaffold greatly enhances the relatively weak affinities of single carbohydrate ligands to the corresponding receptors, and effectively amplifies the carbohydrate-mediated interactions. Glyconanomaterials are thus an appealing platform for biosensing applications. In this review, we discuss the chemistry for conjugation of carbohydrates to nanomaterials, summarize strategies, and tabulate examples of applying glyconanomaterials in in vitro and in vivo sensing applications of proteins, microbes, and cells. The limitations and future perspectives of these emerging glyconanomaterials sensing systems are furthermore discussed.


Deriving effective vaccine allocation strategies for pandemic influenza: Comparison of an agent-based simulation and a compartmental model.
Individuals are prioritized based on their risk profiles when allocating limited vaccine stocks during an influenza pandemic. Computationally expensive but realistic agent-based simulations and fast but stylized compartmental models are typically used to derive effective vaccine allocation strategies. A detailed comparison of these two approaches, however, is often omitted. We derive age-specific vaccine allocation strategies to mitigate a pandemic influenza outbreak in Seattle by applying derivative-free optimization to an agent-based simulation and also to a compartmental model. We compare the strategies derived by these two approaches under various infection aggressiveness and vaccine coverage scenarios. We observe that both approaches primarily vaccinate school children, however they may allocate the remaining vaccines in different ways. The vaccine allocation strategies derived by using the agent-based simulation are associated with up to 70% decrease in total cost and 34% reduction in the number of infections compared to the strategies derived by using the compartmental model. Nevertheless, the latter approach may still be competitive for very low and/or very high infection aggressiveness. Our results provide insights about potential differences between the vaccine allocation strategies derived by using agent-based simulations and those derived by using compartmental models.


Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury.
Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca2+- activated K+ channel, KCa3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent KCa3.1 inhibitor. In primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL-1β release. In vivo, senicapoc showed high CNS penetrance and when administered to rats with peripheral nerve injury, it significantly reversed tactile allodynia similar to the standard of care, gabapentin. In contrast to gabapentin, senicapoc achieved efficacy without any overt impact on locomotor activity. Together, the data demonstrate that the KCa3.1 inhibitor senicapoc is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury.


Ileal apparent protein and amino acid digestibilities and endogenous nitrogen losses in pigs fed soybean and rapeseed products.
We investigated the effects of various protein sources on the apparent ileal digestibilities (AID) of CP and amino acids (AA) and on the recoveries of ileal endogenous nitrogen (N) in pigs. Ileal endogenous N losses (ENL) were measured using the 15N-isotope dilution method. Thirteen pigs (BW of 13 to 20 kg) were fitted with a post-valve-T-cecal cannula and two indwelling blood catheters. They were fed twice daily at a level of 2.6 times ME for maintenance. Cornstarch-based diets contained a soy concentrate (SC; 180.5 g/kg), soybean meal (SBM; 295 g/kg), or a mixture of toasted and untoasted soybean meal (mSBM; 330.4 g/kg) in Trial I or three rapeseed cakes, dehulled-toasted (RC1; 395 g/kg), non-dehulled-toasted (RC2; 458 g/kg), and dehulled-untoasted (RC3; 390 g/kg) in Trial II. The protein sources provided diets with similar levels of apparent ileal digestible CP (108 g/kg as-fed diet) and Lys, Met+Cys, Thr, and Trp. The AID of CP was greater (P < .05) for the SC (86.8%) and SBM (82.8%) than for the SBM (68.1%) diet. In Trial II, the AID of CP was greater (P < .05) for RC1 (76.2%) and RC3 (75.8%) than for the RC2 (69.5%) diet. For all diets, the differences in the AID for most of the AA corresponded to the differences in the AID of CP. The ENL (g/kg DMI) were greater (P < .05) for the mSBM diet (3.75) than for the SC (2.53) and SBM (2.53) diets in Trial I but were similar (P > .05; 2.24, 3.03, and 2.89 for RC1, RC2, and RC3, respectively) among diets in Trial II. We concluded that AID of CP of the soybean diets were associated with endogenous and dietary N losses. For these diets, increased ENL and dietary N losses were associated with a higher dietary trypsin inhibitor activity. For the rapeseed diets, dehulling increased AID of CP and AA, due to reduced ENL (P = .08) and dietary N losses (P < .05). Toasting of dehulled rapeseed cake did not affect the AID of CP and AA (P > .05) while reducing the true ileal CP digestibility (P < .05).


Association between fruit, vegetable, seafood, and dairy intake and a reduction in the prevalence of type 2 diabetes in Qingdao, China.
Fruit, vegetable, seafood, and dairy intake may reduce the risk of type 2 diabetes, but this relationship is unclear. We aimed to examine the associations between fruit, vegetable, seafood, and dairy intake and type 2 diabetes prevalence in a Chinese population. A total of 4,343 individuals aged 35-74 years participated in a population-based cross-sectional study in Qingdao, China. The frequency and quantity of fruit, vegetable, seafood, and dairy intake were determined using a standard food frequency questionnaire. Diabetes was classified according to the WHO/IDF 2006 criteria. Logistic regression analysis was employed to estimate odds ratio (OR) for type 2 diabetes in relation to fruit, vegetable, seafood, and dairy intake in a multivariable model. The multivariate-adjusted ORs (95% confidence interval) for the presence of type 2 diabetes were 0.68 (0.46-0.98), 0.50 (0.37-0.68), and 0.91 (0.66-1.25), respectively, for the highest versus the lowest groups regarding total fruit and vegetable, fruit or vegetable intake in women. The ORs for type 2 diabetes prevalence regarding the quantity of fruit and vegetable, fruit, and yogurt intake were 0.88 (0.78-0.99), 0.71 (0.61-0.82), and 0.56 (0.32-0.98) in women, but not in men. Seafood consumption was inversely associated with diabetes risk in men, but not in women; the corresponding figures were 0.58 (0.35-0.96) and 0.92 (0.63-1.36), respectively. Fruit, vegetable, and yogurt intake in women and seafood intake in men were inversely associated with type 2 diabetes prevalence in this Chinese population. These findings require confirmation in a prospective study.


Mobility and adjustments: paths to the resolution of residential stress.
In theory, residential mobility is a response to environmental stress only if households do not reduce dissatisfaction through other alternatives, such as housing improvements or repairs. Despite the attention given to stress-reducing alternatives, however, no attempt has been made to test empirically the residential satisfaction model with adjustments. Using data from the Annual Housing Survey: 1978-1981, I model three stages in the mobility process and investigate potential sources of specification error in previous tests. Blocks of family cycle, background/action state, and location/housing variables are shown to affect adjusting significantly. Residential satisfaction strongly affects mobility preferences; and all theoretically relevant blocks of explanatory variables predict mobility. Alternatives to mobility should be included in the residential satisfaction model.


Public health consequences of terrorism on maternal-child health in New York City and Madrid.
Past research provides evidence for trajectories of health and wellness among individuals following disasters that follow specific pathways of resilience, resistance, recovery, or continued dysfunction. These individual responses are influenced by event type and pre-event capacities. This study was designed to utilize the trajectories of health model to determine if it translates to population health. We identified terrorist attacks that could potentially impact population health rather than only selected individuals within the areas of the attacks. We chose to examine a time series of population birth outcomes before and after the terrorist events of the New York City (NYC) World Trade Center (WTC) attacks of 2001 and the Madrid, Spain train bombings of 2004 to determine if the events affected maternal-child health of those cities and, if so, for how long. For percentages of low birth weight (LBW) and preterm births, we found no significant effects from the WTC attacks in NYC and transient but significant effects on rates of LBW and preterm births following the bombings in Madrid. We did find a significant positive and sustained effect on infant mortality rate in NYC following the WTC attacks but no similar effect in Madrid. There were no effects on any of the indicator variables in the comparison regions of New York state and the remainder of Spain. Thus, population maternal-health in New York and Madrid showed unique adverse effects after the terrorist attacks in those cities. Short-term effects on LBW and preterm birth rates in Madrid and long-term effects on infant mortality rates in NYC were found when quarterly data were analyzed from 1990 through 2008/2009. These findings raise questions about chronic changes in the population's quality of life following catastrophic terrorist attacks. Public health should be monitored and interventions designed to address chronic stress, environmental, and socioeconomic threats beyond the acute aftermath of events.


Hormone therapy for radiorecurrent prostate cancer.
The management of patients who relapse after radical radiotherapy is a challenging problem for the multidisciplinary team. This group of men may have been considered ineligible or chosen not to be treated with an initial surgical approach as a result of high-risk features or significant comorbid conditions. It is important not to miss the opportunity for definitive local salvage therapies at this stage, and eligible patients should undergo careful restaging to determine their suitability for these approaches. For those men not suitable for local treatment, androgen deprivation therapy (ADT) remains an option. Literature review of the evidence relating to the management of hormone therapy for radiorecurrent prostate cancer. Results from retrospective studies have shown that not all men with biochemical relapse will experience distant metastasis or a reduction in survival due to prostate cancer progression. Therefore, the timing of ADT commencement remains controversial. However, it would seem appropriate to offer immediate therapy to men with advanced disease or unfavourable prostate-specific antigen (PSA) kinetics at relapse. Patients with more favourable risk factors and PSA kinetics may be considered for watchful waiting and deferred ADT to avoid or delay the associated toxicities. Patients with non-metastatic disease can be given the option of castration-based therapy or an antiandrogen such as bicalutamide which may have potential advantages in maintenance of sexual function, physical capacity and bone mineral density but at the expense of an increase in gynaecomastia and mastalgia. Recent data suggest the burden of toxicity from ADT may be reduced by the use of intermittent hormone therapy without compromising survival in this group of patients with radiorecurrence. Hormone therapy remains an option for men with radiorecurrent prostate cancer.


Sickle cell disease.
Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.


Integrating Radio-Over-Fiber Communication System and BOTDR Sensor System.
In this paper, we propose and experimentally demonstrate for the first time, the integration of a radio-over-fiber (RoF) communication system and a Brillouin optical time-domain reflectometry (BOTDR) distributed sensor system using a single optical fiber link. In this proof-of-concept integrated system, the communication system is composed of three modulation formats of quadrature phase-shift keying (QPSK), 16-quadrature amplitude modulation (16-QAM) and 64-QAM, which are modulated onto an orthogonal frequency division multiplexing (OFDM) signal. Whereas, the BOTDR sensor system is used for strain and/or temperature monitoring over the fiber distance with a spatial resolution of 5 m using a 25 km single-mode silica fiber. The error vector magnitude (EVM) is analyzed in three modulation formats in the presence of various BOTDR input pump powers. Using QPSK modulation, optimized 18 dBm sensing and 10 dBm data power, the measured EVM values with and without bandpass filter are 3.5% and 14.5%, respectively. The proposed system demonstrates a low temperature measurement error (±0.49 °C at the end of 25 km) and acceptable EVM values, which were within the 3GPP requirements. The proposed integrated system can be effectively applied for practical applications, which significantly reduces the fiber infrastructure cost by effective usage of a single optical fiber link.