Evaluating the impact of anatomical and physiological variability on human equivalent doses using PBPK models.

Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure (PODs) for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.

Prevalence and prevention of suicidal ideation among asylum seekers in a high-risk urban post-displacement setting.

AIMS: Among asylum seekers in a high-risk unstable post-displacement context, we aimed to investigate the prevalence of and risk for suicidal ideation (study 1), and then to test whether and how Mindfulness-Based Trauma Recovery for Refugees (MBTR-R) may prevent or treat suicidal ideation (study 2). METHODS: Study 1 was conducted among a community sample of N = 355 (31.8% female) East African asylum seekers in a high-risk urban post-displacement setting in the Middle East (Israel). Study 2 was a secondary analysis of a randomised waitlist-control trial of MBTR-R among 158 asylum-seekers (46.2% female) from the same community and post-displacement setting. RESULTS: Prevalence of suicidal ideation was elevated (31%). Post-migration living difficulties, as well as posttraumatic stress, depression, anxiety and their multi-morbidity were strongly associated with suicidal ideation severity. Likewise, depression and multi-morbidity prospectively predicted the onset of suicidal ideation. Relative to its incidence among waitlist-control (23.1%), MBTR-R prevented the onset of suicidal ideation at post-intervention assessment (15.6%) and 5-week follow-up (9.8%). Preventive effects of MBTR-R on suicidal ideation were mediated by reduced posttraumatic stress, depression, anxiety and their multi-morbidity. MBTR-R did not therapeutically reduce current suicidal ideation present at the beginning of the intervention. CONCLUSIONS: Findings warn of a public health crisis of suicidality among forcibly displaced people in high-risk post-displacement settings. Although preliminary, novel randomised waitlist-control evidence for preventive effects of MBTR-R for suicidal ideation is promising. Together, findings indicate the need for scientific, applied and policy attention to mental health post-displacement in order to prevent suicide among forcibly displaced people.

Flood Risk to Hospitals on the United States Atlantic and Gulf Coasts From Hurricanes and Sea Level Rise.

Hurricanes have caused major healthcare system disruptions. No systematic assessment of hurricane risk to United States hospital-based healthcare delivery has been performed. Here, we show that 25 of 78 metropolitan statistical areas (MSAs) on the United States Atlantic and Gulf Coasts have half or more of their hospitals at risk of flooding from relatively weak hurricanes. 0.82 m of sea level rise expected within this century from climate change increases the odds of hospital flooding 22%. Furthermore, in 18 MSAs at least half of the roads within 1.6 km of hospitals were at risk of flooding from a category 2 storm. These findings identify previously undescribed risks to hospital-based care delivery in Atlantic and Gulf Coast communities. They suggest that lower intensity hurricanes can have outsized impacts on healthcare access, particularly in places where per capita bed availability is low.

Diagnosis of Schizophrenia Based on the Data of Various Modalities: Biomarkers and Machine Learning Techniques (Review).

Schizophrenia is a socially significant mental disorder resulting frequently in severe forms of disability. Diagnosis, choice of treatment tactics, and rehabilitation in clinical psychiatry are mainly based on the assessment of behavioral patterns, socio-demographic data, and other investigations such as clinical observations and neuropsychological testing including examination of patients by the psychiatrist, self-reports, and questionnaires. In many respects, these data are subjective and therefore a large number of works have appeared in recent years devoted to the search for objective characteristics (indices, biomarkers) of the processes going on in the human body and reflected in the behavioral and psychoneurological patterns of patients. Such biomarkers are based on the results of instrumental and laboratory studies (neuroimaging, electro-physiological, biochemical, immunological, genetic, and others) and are successfully being used in neurosciences for understanding the mechanisms of the emergence and development of nervous system pathologies. Presently, with the advent of new effective neuroimaging, laboratory, and other methods of investigation and also with the development of modern methods of data analysis, machine learning, and artificial intelligence, a great number of scientific and clinical studies is being conducted devoted to the search for the markers which have diagnostic and prognostic value and may be used in clinical practice to objectivize the processes of establishing and clarifying the diagnosis, choosing and optimizing treatment and rehabilitation tactics, predicting the course and outcome of the disease. This review presents the analysis of the works which describe the correlates between the diagnosis of schizophrenia, established by health professionals, various manifestations of the psychiatric disorder (its subtype, variant of the course, severity degree, observed symptoms, etc.), and objectively measured characteristics/quantitative indicators (anatomical, functional, immunological, genetic, and others) obtained during instrumental and laboratory examinations of patients. A considerable part of these works has been devoted to correlates/biomarkers of schizophrenia based on the data of structural and functional (at rest and under cognitive load) MRI, EEG, tractography, and immunological data. The found correlates/biomarkers reflect anatomic disorders in the specific brain regions, impairment of functional activity of brain regions and their interconnections, specific microstructure of the brain white matter and the levels of connectivity between the tracts of various structures, alterations of electrical activity in various parts of the brain in different EEG spectral ranges, as well as changes in the innate and adaptive links of immunity. Current methods of data analysis and machine learning to search for schizophrenia biomarkers using the data of diverse modalities and their application during building and interpretation of predictive diagnostic models of schizophrenia have been considered in the present review.

Ligamentous healing potential of the acromioclavicular ligament following acute anatomical reconstruction.

BACKGROUND: Horizontal instability following acute acromioclavicular joint (ACJ) reconstruction still occurs with a high prevalence. Although the human acromioclavicular ligament complex (ACLC) represents the major horizontal ACJ stabilizer, experimental studies on healing characteristics are lacking. Therefore, the purpose of this histological study was to investigate the healing potential of the ACLC following acute anatomical reconstruction METHODS: In this prospective clinical-experimental study, 28 ACLC biopsies were performed in patients with complete ACJ dislocations (Rockwood type 4 or 5) during acute hook plate stabilization (IG: implantation group; n = 14) and hook plate removal (EG: explantation group; n = 14). Histological analyses included Giemsa staining, polarized light microscopy and immunostaining against CD68, αSMA and collagen type I and type III. Histomorphological evaluation entailed cell counts, collagen expression score, ligament tissue maturity index (LTMI) and descriptive analysis of specific ligamentous structures. Statistics consisted of nonparametric Mann-Whitney U tests and a level of significance of P < .05. RESULTS: Total cell counts (cells/mm2 1491 ± 296 vs. 635 ± 430; P < 0.001) and collagen III expression (3.22 ± 0.22 vs. 1.78 ± 0.41; P < 0.001) were higher in EG compared to IG. Inversely αSMA + (11 ± 9 vs. 179 ± 186; P < 0.001) and CD68 + cell counts (56 ± 20 vs. 100 ± 57; P 0.009) were significantly lower in the EG. The EG revealed a comparable reorientation of ligamentous structures. Consistently, ACLC samples of the EG (21.6 ± 2.4) displayed a high total but differently composed LTMI score (IG: 24.5 ± 1.2; P < 0.001). CONCLUSIONS: This experimental study proved the ligamentous healing potential of the human ACLC following acute anatomical reconstruction. Histomorphologically, the ACLC reliably showed a ligamentous state of healing at a mean of about 12 weeks after surgery. However, processes of ligamentous remodeling were still evident. These experimental findings support recent clinical data showing superior horizontal ACJ stability with additional AC stabilization in the context of acute ACJ reconstruction. Though, prospective clinical and biomechanical studies are warranted to evaluate influencing factors on ACLC healing and potential impacts of acute ACLC repair on clinical outcome. STUDY TYPE: Controlled Laboratory Study.

The tissue-renin-angiotensin-system of the human intervertebral disc.

Symptomatic intervertebral disc (IVD) degeneration accounts for significant socioeconomic burden. Recently, the expression of the tissue renin-angiotensin system (tRAS) in rat and bovine IVD was demonstrated. The major effector of tRAS is angiotensin II (AngII), which participates in proinflammatory pathways. The present study investigated the expression of tRAS in human IVDs, and the correlation between tRAS, inflammation and IVD degeneration. Human IVD tissue was collected during spine surgery and distributed according to principal diagnosis. Gene expression of tRAS components, proinflammatory and catabolic markers in the IVD tissue was assessed. Hydroxyproline (OHP) and glycosaminoglycan (GAG) content in the IVD tissue were determined. Tissue distribution of tRAS components was investigated by immunohistochemistry. Gene expression of tRAS components such as angiotensin-converting enzyme (ACE), Ang II receptor type 2 (AGTR2), angiotensinogen (AGT) and cathepsin D (CTSD) was confirmed in human IVDs. IVD samples that expressed tRAS components (n = 21) revealed significantly higher expression levels of interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5 compared to tRAS-negative samples (n = 37). Within tRAS-positive samples, AGT, matrix-metalloproteinases 13 and 3, IL-1, IL-6 and IL-8 were more highly expressed in traumatic compared to degenerated IVDs. Total GAG/DNA content of non-tRAS expressing IVD tissue was significantly higher compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD. The present study identified the existence of tRAS in the human IVD and suggested a correlation between tRAS expression, inflammation and ultimately IVD degeneration.

Immunohistochemical analysis of sensory corpuscles in human transplants of the anterior cruciate ligament.

BACKGROUND: Sensory nerve endings in ligaments play an important role for the proprioceptive function. Clinical trials show that the sense of body position does not fully recover in the knee joint after reconstructive surgery of the ruptured anterior cruciate ligament. The aim of this study is to identify sensory corpuscles in autogenous and allogenous transplants of the ligament and to compare their quantity between the used allografts and autografts. METHODS: Thirty-three patients were included in this study. Three patellar tendon allografts, 14 patellar tendon autografts and 12 semitendinosus autografts were harvested during revision surgery after traumatic rerupture of the graft. The control consisted of 4 healthy anterior cruciate ligaments after fresh rupture. After haematoxylin staining, immunohistochemical analysis was performed using antibodies against S100, p75 and PGP9.5. Microscopical examination was carried out, and the number of mechanoreceptors was counted. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Two types of mechanoreceptors were identified in each graft: Ruffini corpuscles and free nerve endings. The number of Ruffini corpuscles per square centimeter was the highest in the control. Comparing the grafts, the highest number of receptors could be detected in the semitendinosus autograft. The amount of free nerve endings was higher in the semitendinosus and patellar tendon autografts than in the control; the allografts showed the lowest number of receptors. With increasing time after reconstruction, the number of both types of receptors showed a decrease in the semitendinosus graft, whereas it increased in the patellar tendon graft and allograft. The number of mechanoreceptors in the semitendinosus and patellar tendon graft decreased over time after graft-failure, whereas it increased slightly in the allograft. CONCLUSION: This study was the first to identify mechanoreceptors in human transplants of the anterior cruciate ligament. The partial increase in the number of receptors over time after reconstruction could indicate a reinnervation of the grafts.

Free-ranging wild boar (Sus scrofa) in Switzerland: casual observations and model-based projections during open and closed season for hunting.

INTRODUCTION: Wild boar (i.e., Sus scrofa) are susceptible to a range of diseases that can be transmitted to domestic pigs. Assessing the potential risk of transmission-related events involves identifying where wild boar occur in Switzerland and where they still can colonize. It also involves identifying zones where piggeries are dense. In the work presented here, the distribution of wild boar in Switzerland was projected from grid data as probabilities of presence using an approach based on statistical modeling, separately for closed and open season for hunting. The predicted probabilities of wild boar presence were related to the density of piggeries in the six agricultural zones. The resulting maps show how the potential risk of transmission-related events, as a proxy for disease transmission, is distributed in Switzerland. Wild boar presence data consisted of hunting data and casual observations recorded from September 2011 to February 2018 at the coordinate level. They were obtained from all 16 Swiss cantons maintaining a license hunting system plus Solothurn (for 2017) and Zurich, as well as from info fauna. The probability of wild boar occurrence was high (> 0.7) in Jura, the valleys of the Southern Alps, the Rhone Valley down the river from Martigny, and the Rhine Valley down the river from Bündner Herrschaft; it was fair (0.5-0.7) in the Swiss Plateau. These regions broadly overlap agricultural zones with a high density of piggeries. Patches of perennially suitable, but currently not colonized habitat were found in the cantons of Berne, Obwalden, Uri, Schwyz, Glarus, and Grisons. The probability of wild boar occurrence across the entire study area, including the Alps, increased by 12% during closed season for hunting. The results were discussed with reference to similar studies.

INTRODUCTION: Le sanglier (Sus scrofa) est sensible à plusieurs maladies qui peuvent être transmises au cochon domestique. Afin d'estimer le risque potentiel de transmission, il est important d'identifier les zones occupées par le sanglier en Suisse ainsi que celles qu'il pourrait encore coloniser. De plus, cela implique également de pouvoir situer les secteurs où les élevages de cochons sont les plus abondant. Dans le présent travail, la distribution du sanglier a été projetée selon une grille à l'échelle de la Suisse à partir des présences confirmées en utilisant des méthodes statistiques, ceci en considérant la période d'ouverture de chasse d'une part et la période de fermeture d'autre part. Les probabilités de présence calculées ont été misent en relation avec la densité des porcheries dans les différentes zones agricoles. Les cartes résultant de cet exercice montrent comment le risque potentiel de transmission de maladies est distribué en Suisse. La base de données utilisée contenait des informations sur les sangliers tirés lors de la chasse, ainsi que des observations occasionnelles, rapportées à l'échelle de la coordonnée entre Septembre 2011 et Février 2018. Ces données ont étés obtenues de l'ensemble des 16 cantons maintenant un système de chasse à patente, plus Soleure (2017) et Zurich, et des données disponibles sur info fauna. La probabilité de trouver des sanglier est élevée (> 0.7) dans le Jura, les vallées du sud des Alpes, la vallée du Rhône en aval de Martigny et la vallée du Rhin en aval de Bündner Herrschaft. Elle est modérée (0.5­0.7) pour le Plateau Suisse. Ces régions correspondent à peu près aux zones agricoles possédant les plus grandes densités de porcheries. Des secteurs offrant des conditions favorables toute l'année, mais encore inoccupés par le sanglier ont été trouvés dans les cantons de Berne, Obwald, Uri, Schwyz, Glaris et les Grisons. Sur l'ensemble de la zone d'étude, la probabilité de présence des sangliers était supérieur de 12% en dehors de la période de chasse. Les résultats ont été discutés en les comparant à des études similaires.

Low-Energy Physics Reach of Xenon Detectors for Nuclear-Recoil-Based Dark Matter and Neutrino Experiments.

Dual-phase xenon detectors lead the search for keV-scale nuclear recoil signals expected from the scattering of weakly interacting massive particle (WIMP) dark matter, and can potentially be used to study the coherent nuclear scattering of MeV-scale neutrinos. New capabilities of such experiments can be enabled by extending their nuclear recoil searches down to the lowest measurable energy. The response of the liquid xenon target medium to nuclear recoils, however, is not well characterized below a few keV, leading to large uncertainties in projected sensitivities. In this work, we report a new measurement of ionization signals from nuclear recoils in liquid xenon down to the lowest energy reported to date. At 0.3 keV, we find that the average recoil produces approximately one ionization electron; this is the first measurement of nuclear recoil signals at the single-ionization-electron level, approaching the physical limit of liquid xenon ionization detectors. We discuss the implications of these measurements on the physics reach of xenon detectors for nuclear-recoil-based WIMP dark matter searches and the detection of coherent elastic neutrino-nucleus scattering.

Results of a Search for Sub-GeV Dark Matter Using 2013 LUX Data.

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

Diagnosis of warm dense conditions in foil targets heated by intense femtosecond laser pulses using Kα imaging spectroscopy.

Warm dense conditions in titanium foils irradiated with intense femtosecond laser pulses are diagnosed using an x-ray imaging spectroscopy technique. The line shapes of radially resolved titanium Kα spectra are measured with a toroidally bent GaAs crystal and an x-ray charge-coupled device. Measured spectra are compared with the K-shell emissions modeled using an atomic kinetics - spectroscopy simulation code. Kα line shapes are strongly affected by warm (5-40 eV) bulk electron temperatures and imply multiple temperature distributions in the targets. The spatial distribution of temperature is dependent on the target thickness, and a thin target shows an advantage to generate uniform warm dense conditions in a large area.

Release behavior of VAN from four types of CaP-ceramic granules using various loading methods at two different degrees of acidity.

The release behavior of vancomycin (VAN) from beta-tricalciumphosphate (ßTCP), hydroxyapatite (HA), glass ceramic (GC) and sponge-like collagen ßTCP granule composite (sponge) was studied. Vacuum and drip loading methods were compared. The influence of VAN concentration and pH on release behavior was analyzed with respect to a stable release level of VAN above the minimum inhibitory concentration over 14 days. Initially the morphology of the granule carrier systems was examined with ESEM, stereomicroscopy, µCT-imaging and Camsizer® regarding porosity, interconnecting pores and granule size. Drug release patterns following a vacuum and a drip loading method with VAN at concentrations of 5 and 50 mg/ml were compared. The influence of pH 7.4 compared to pH 5.0 on release behavior was studied. The drug was released in bidistilled water at 37 °C, the concentration determined by photometry at 220 nm. For statistical purposes, the mean and standard deviation were calculated and analyzed by Origin 9.1 Professional SR1 (OriginLab). Due to low interconnectivity and low porosity, the vacuum loading method was unable to attain complete drug loading of the ceramic granules. The sponge showed an inhomogeneous distribution of ßTCP granules. Drug release was high at pH 7.4, at pH 5.0 it practically did not occur. All samples except for the collagen-complex show an initial VAN burst release with a following steady release. Loading with 5 mg/ml concentrated VAN resulted in a higher percentage of available drug being released. However, when loaded with 50 mg/ml, the absolute amount of drug released was higher.

Limits on Spin-Dependent WIMP-Nucleon Cross Section Obtained from the Complete LUX Exposure.

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=1.6×10^{-41} cm^{2} (σ_{p}=5×10^{-40} cm^{2}) at 35 GeV c^{-2}, almost a sixfold improvement over the previous LUX spin-dependent results. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

First Searches for Axions and Axionlike Particles with the LUX Experiment.

The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.

Results from a Search for Dark Matter in the Complete LUX Exposure.

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

High velocity suspension flame spraying (HVSFS) of metal doped bioceramic coatings.

•Bioceramic coatings doped with metals for antibacterial effect.•Combination of suspension and precursor flame spraying.•Successful deposition of submicron metallic particles in bioceramic matrix.

A Single Dose of the Anti-Resorptive Peptide Human Calcitonin Paradoxically Augments Particle- and Endotoxin-Mediated Pro-Inflammatory Cytokine Production In Vitro.

The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10(-9) M). Cytokine production of tumour necrosis factor (TNF)-α was quantified on both RNA and protein levels while interleukins (IL)-1ß and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-α mRNA production and protein secretion of TNF-α, IL-1ß, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti-resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined.

Improved Limits on Scattering of Weakly Interacting Massive Particles from Reanalysis of 2013 LUX Data.

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4} kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium ß source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c^{-2}, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c^{-2} WIMP mass.

Results on the Spin-Dependent Scattering of Weakly Interacting Massive Particles on Nucleons from the Run 3 Data of the LUX Experiment.

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4} kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9.4×10^{-41} cm^{2} (σ_{p}=2.9×10^{-39} cm^{2}) at 33 GeV/c^{2}. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

The relationship between challenging behaviours, mood and interest/pleasure in adults with severe and profound intellectual disabilities.

BACKGROUND: We investigated whether current mood and interest/pleasure ratings in adults with moderate to profound intellectual disabilities were predictive of challenging behaviour [self-injurious behaviour (SIB), aggressive/destructive behaviour and stereotypic behaviour] and vice versa. METHOD: In this combined cross-sectional and longitudinal study, staff members of a Hungarian residential facility completed translated versions of the Behaviour Problems Inventory-Short Form (BPI-S), the Challenging Behaviour Interview (CBI) and the Mood, Interest and Pleasure Questionnaire-Short Form (MIPQ-S) for 50 participants at two time points, approximately 4 to 5 months apart. RESULTS: Bivariate correlations from data concurrently assessed at Time-1 showed significant linear relationships between the SIB (both frequency and severity scores) and Interest/Pleasure sub-scales, and the Aggressive/Destructive Behaviour (severity scores) and the MIPQ-S Mood sub-scales (unadjusted for multiple correlations). All of these effects were found with the BPI-S data, but not with the CBI. Multiple regression analyses revealed that (1) low interest/pleasure assessed at Time-1 predicted high SIB (frequency and severity) at Time-2. (2) Interest/pleasure was not predictive of aggressive or stereotypic behaviour. (3) Mood at Time-1 did not predict any of the three types of behaviour problems at Time-2. (4) In reverse, high SIB (frequency and severity) at Time-1 predicted low interest/pleasure ratings at Time-2. (5) Surprisingly, frequent aggressive/destructive behaviour predicted high interest/pleasure. (6) Stereotypic behaviour scores at Time-1 did not predict interest/pleasure ratings at Time-2. Again, all of these effects were only found with the BPI-S data, but not with the CBI. Internal consistency, test-retest reliability and concurrent validity of the Hungarian versions of all three questionnaires had generally satisfactory outcomes. DISCUSSION: The fact that increasingly frequent and severe SIB was predicted by declining measures of interest/pleasure is consistent with previous studies. Contrary to those earlier studies, however, we found that SIB was not predicted by mood and that aggressive/destructive behaviour actually predicted future elevated mood. Implications for future research regarding the directional relationship between affective states such as mood and interest and pleasure, on the one hand, and challenging behaviour, on the other, were discussed.