Soldiers initiate foraging activities in the subterranean termite, Heterotermes tenuis.
Caste polyethism has been recorded in some termite species, however the foraging behavior of subterranean termites remains poorly known. Heterotermes tenuis Hagen (Isoptera: Rhinotermitidae) is a subterranean termite that is native to Brazil and is an agricultural and urban pest. The aim of this study was to investigate which caste acts as scouts when searching for food sources and determinate the percentages of each caste present in the foraging territories of field colonies of H. tenuis. Our results showed no significant differences among the caste proportions present in the foraging territories of the three colonies studied in the field. Laboratory experiments showed that minor soldiers were the most frequent initiators of foraging activities. This result suggests that the exploratory phase of the foraging behavior may be regulated by the number of soldiers present in the foraging territories of each colony.


Gradient-based enhancement of tubular structures in medical images.
Vesselness filters aim at enhancing tubular structures in medical images. The most popular vesselness filters are based on eigenanalyses of the Hessian matrix computed at different scales. However, Hessian-based methods have well-known limitations, most of them related to the use of second order derivatives. In this paper, we propose an alternative strategy in which ring-like patterns are sought in the local orientation distribution of the gradient. The method takes advantage of symmetry properties of ring-like patterns in the spherical harmonics domain. For bright vessels, gradients not pointing towards the center are filtered out from every local neighborhood in a first step. The opposite criterion is used for dark vessels. Afterwards, structuredness, evenness and uniformness measurements are computed from the power spectrum in spherical harmonics of both the original and the half-zeroed orientation distribution of the gradient. Finally, the features are combined into a single vesselness measurement. Alternatively, a structure tensor that is suitable for vesselness can be estimated before the analysis in spherical harmonics. The two proposed methods are called Ring Pattern Detector (RPD) and Filtered Structure Tensor (FST) respectively. Experimental results with computed tomography angiography data show that the proposed filters perform better compared to the state-of-the-art.


Language and life history: a new perspective on the development and evolution of human language.
It has long been claimed that Homo sapiens is the only species that has language, but only recently has it been recognized that humans also have an unusual pattern of growth and development. Social mammals have two stages of pre-adult development: infancy and juvenility. Humans have two additional prolonged and pronounced life history stages: childhood, an interval of four years extending between infancy and the juvenile period that follows, and adolescence, a stage of about eight years that stretches from juvenility to adulthood. We begin by reviewing the primary biological and linguistic changes occurring in each of the four pre-adult ontogenetic stages in human life history. Then we attempt to trace the evolution of childhood and juvenility in our hominin ancestors. We propose that several different forms of selection applied in infancy and childhood; and that, in adolescence, elaborated vocal behaviors played a role in courtship and intrasexual competition, enhancing fitness and ultimately integrating performative and pragmatic skills with linguistic knowledge in a broad faculty of language. A theoretical consequence of our proposal is that fossil evidence of the uniquely human stages may be used, with other findings, to date the emergence of language. If important aspects of language cannot appear until sexual maturity, as we propose, then a second consequence is that the development of language requires the whole of modern human ontogeny. Our life history model thus offers new ways of investigating, and thinking about, the evolution, development, and ultimately the nature of human language.


Pain assessment: subjectivity, objectivity, and the use of neurotechnology.
The pain clinician is confronted with the formidable task of objectifying the subjective phenomenon of pain so as to determine the right treatments for both the pain syndrome and the patient in whom the pathology is expressed. However, the experience of pain - and its expression - remains enigmatic. Can currently available evaluative tools, questionnaires, and scales actually provide adequately objective information about the experiential dimensions of pain? Can, or will, current and future iterations of biotechnology - whether used singularly or in combination (with other technologies as well as observational-behavioral methods) - afford objective validation of pain? And what of the clinical, ethical, legal and social issues that arise in and from the use - and potential misuse - of these approaches? Subsequent trajectories of clinical care depend upon the findings gained through the use of these techniques and their inappropriate employment - or misinterpretation of the results they provide - can lead to misdiagnoses and incorrect treatment. This essay is the first of a two-part series that explicates how the intellectual tasks of knowing about pain and the assessment of its experience and expression in the pain patient are constituent to the moral responsibility of pain medicine. Herein, we discuss the problem of pain and its expression, and those methods, techniques, and technologies available to bridge the gap between subjective experience and objective evaluation. We address how these assessment approaches are fundamental to apprehend both pain as an objective, neurological event, and its impact upon the subjective experience, existence, and expectations of the person in pain. In this way, we argue that the right use of technology - together with inter-subjectivity, compassion, and insight - can sustain the good of pain care as both a therapeutic and moral enterprise.


Adverse Events in the Operating Room: Definitions, Prevalence, and Characteristics. A Systematic Review.
Adverse events occur commonly in the operating room (OR) and often contribute to morbidity, mortality, and increased healthcare spending. Validated frameworks to measure and report postoperative outcomes have long existed to facilitate exchanges of structured information pertaining to postoperative complication rates in order to improve patient safety. However, systematic evidence regarding measurement and reporting of intraoperative adverse events (iAE) is still lacking. We searched Ovid Medline, Embase, and Cochrane databases for articles published up to June 2016 that measured and reported iAE. We presented the terms and definitions used to describe iAE. We identified the types of reported iAE and summarized them into discrete categories. We reported frequencies of iAE by detection methods. Of the 47 included studies, 30 were cross-sectional, 14 were case-series, and 3 were cohort studies. The studies used 16 different terms and 22 unique definitions to describe 74 types of iAE. Frequencies of iAE appeared to vary depending on the detection methods, with higher numbers reported when direct observation in the OR was used to detect iAE. Twenty studies assessed severity of iAE, which were mostly based on whether they resulted in postoperative outcomes. This study systematically reviewed the current evidence on prevalence and characteristics of iAE that were detected by direct observation, reviews of patient charts, administrative data and incident reports, and surveys and interviews of healthcare providers. Our findings suggest that direct observation method has the most potential to identify and characterize iAE in detail.


Culture conditions influence satellite cell activation and survival of single myofibers.
Single myofiber isolation protocols allow to obtain an in vitro system in which the physical association between the myofiber and its stem cells, the satellite cells, is adequately preserved. This technique is an indispensable tool by which the muscle regeneration process can be recapitulated and studied in each specific phase, from satellite cell activation to proliferation, from differentiation to fusion. This study aims to clarify the effect of different culture conditions on single myofibers, their associated satellite cells, and the physiological behavior of the satellite cells upon long term culture. By direct observations of the cultures, we compared different experimental conditions and their effect on both satellite cell behavior and myofiber viability.


Coffee consumption and risk of aortic valve stenosis: A prospective study.
Coffee contains many biologically active compounds with potential adverse or beneficial effects on the cardiovascular system. Whether coffee consumption is associated with the risk of aortic valve stenosis (AVS) is unknown. The purpose of this study was therefore to examine the association between coffee consumption and AVS incidence. This prospective study included 71 178 men and women who provided information on their coffee consumption through a questionnaire at baseline. Incident cases of AVS were identified through linkage with the Swedish National Patient and Cause of Death Registers. During a mean follow-up of 15.2 years, 1295 participants (777 men and 518 women) were diagnosed with AVS. Coffee consumption was positively associated with risk of AVS in a dose-response manner after adjustment for age, sex, smoking, and other risk factors (P-trend = 0.005). The multivariable hazard ratios were was 1.11 (95% confidence interval 1.04-1.19) per 2 cups/day increase of coffee consumption and 1.65 (95% confidence interval 1.10-2.48) when comparing the highest (≥6 cups/day) with the lowest (<0.5 cup/day) category of coffee consumption. The association was not modified by other risk factors. This study provides novel evidence that high coffee consumption is associated with an increased risk of AVS.


Evaluation and management of hepatitis B in pregnancy: a survey of current practices.
Optimal management of hepatitis B (HBV) during pregnancy is unclear. Safety and efficacy data of antiviral therapy are limited. We assessed the practice patterns of hepatologists, gastroenterologists, and other physicians for evaluating and managing pregnant patients with HBV as well as the variation of these practice patterns by primary specialty and practice description. An 18-question electronic survey was sent to physicians with a special interest in liver disease addressing the evaluation and management of HBV during pregnancy. A total of 226 physicians responded, of whom 68.5% characterized their primary specialty as hepatology, 26.5% as gastroenterology, and 4.9% as other; 62.4% were academic-based physicians, and 37.6% were community-based physicians. The average years in practice were 13.3. Initiation of antiviral therapy during pregnancy was supported by 51.8% of respondents. Of those against therapy initiation, 60.4% cited a lack of clear recommendations, 32.1% cited safety concerns, and 7.5% cited a lack of efficacy. For patients on antivirals who desired to become pregnant, 74.8% of respondents would continue antiviral therapy. The most common antiviral used in pregnancy was lamivudine (72.1%). HBV vaccination and HBV immunoglobulin for infants born to mothers with HBV were recommended by 98.7% of respondents; 57.5% would also recommend breastfeeding. If antivirals were being used, only 30.5% of respondents would still recommend breastfeeding. More hepatologists were "very comfortable" (P=.032) managing these patients compared to nonhepatologists. There is significant heterogeneity in the management of pregnant patients with HBV regardless of primary specialty or practice description. This variability likely reflects a lack of data and specific guidelines. Further research and more specific guidelines are needed.


Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies.
We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension (Family Blood Pressure Program). Subjects identified themselves as belonging to one of four major racial/ethnic groups (white, African American, East Asian, and Hispanic) and were recruited from 15 different geographic locales within the United States and Taiwan. Genetic cluster analysis of the microsatellite markers produced four major clusters, which showed near-perfect correspondence with the four self-reported race/ethnicity categories. Of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity. On the other hand, we detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ethnicity--as opposed to current residence--is the major determinant of genetic structure in the U.S. population. Implications of this genetic structure for case-control association studies are discussed.


Fracture strength of machined ceramic crowns as a function of tooth preparation design and the elastic modulus of the cement.
To determine, by means of static fracture testing the effect of the tooth preparation design and the elastic modulus of the cement on the structural integrity of the cemented machined ceramic crown-tooth complex. Human maxillary extracted premolar teeth were prepared for all-ceramic crowns using two preparation designs; a standard preparation in accordance with established protocols and a novel design with a flat occlusal design. All-ceramic feldspathic (Vita MK II) crowns were milled for all the preparations using a CAD/CAM system (CEREC-3). The machined all-ceramic crowns were resin bonded to the tooth structure using one of three cements with different elastic moduli: Super-Bond C&B, Rely X Unicem and Panavia F 2.0. The specimens were subjected to compressive force through a 4mm diameter steel ball at a crosshead speed of 1mm/min using a universal test machine (Loyds Instrument Model LRX.). The load at the fracture point was recorded for each specimen in Newtons (N). These values were compared to a control group of unprepared/unrestored teeth. There was a significant difference between the control group, with higher fracture strength, and the cemented samples regardless of the occlusal design and the type of resin cement. There was no significant difference in mean fracture load between the two designs of occlusal preparation using Super-Bond C&B. For the Rely X Unicem and Panavia F 2.0 cements, the proposed preparation design with a flat occlusal morphology provides a system with increased fracture strength. The proposed novel flat design showed less dependency on the resin cement selection in relation to the fracture strength of the restored tooth. The choice of the cement resin, with respect to its modulus of elasticity, is more important in the anatomic design than in the flat design.


Further clinical clarification of the muscle dysfunction in cervical headache.
The Headache Classification Committee of the International Headache Society listed impairments in cervical muscle function as criteria for headaches of cervical spine origin. Fifteen subjects with cervical headache and 15 controls were tested for the frequency of abnormal responses to passive stretching and abnormal muscle contraction. A new test of cranio-cervical flexion was used to assess the contraction of the deep neck flexors. Results indicated a trend towards a higher frequency of abnormal response to passive stretching of the muscles examined in the cervical headache group but only the upper trapezius proved significantly different to the control group. Deep neck flexor muscle contraction was significantly inferior in the cervical headache group. From the perspective of physical characterization of cervical headache, it appears that response from passive stretch of muscle may not be a strong criterion for cervical headache but deep neck flexor performance may have potential to identify musculoskeletal involvement in headache. The finding may also provide positive directions for conservative treatment of cervical headache.


Effects of dietary supplementation of selenium and iodine on growth performance, carcass characteristics and histology of thyroid gland in goats.
This study assessed the effects of dietary selenium (Se), iodine (I) and a combination of both on growth performance, thyroid gland activity, carcass characteristics and the concentration of iodine and selenium in Longissimus lumborum (LL) muscle in goats. Twenty-four bucks were randomly assigned to four dietary treatments: control (CON), basal diet without supplementation, basal diet + 0.6 mg Se/kg dry matter (DM) (SS), 0.6 mg I/kg DM (IP), or combination of 0.6 mg/kg DM Se and 0.6 mg/kg DM I (SSIP) and fed for 100 days. Animals fed diet SSIP exhibited higher (P < 0.05) body weight and better feed conversion ratio (FCR) than those fed other diets. Dressing percentage of goats fed the supplemented diets was higher (P < 0.05) than that of the control. Carcasses from the IP group had higher (P < 0.05) total fat proportion than the SSIP group. The levels of both elements were significantly elevated (P < 0.05) in LL muscle in supplemented goats. Thyroid follicular epithelial cells of IP and SSIP animals were significantly higher than those of CON and SS groups. The study demonstrated that the combined Se and I dietary supplementation improves growth performance, carcass dressing percentage and increases the retention of Se and I in goat meat.


Metabolic engineering to enhance bacterial hydrogen production.
Hydrogen fuel is renewable, efficient and clean, and fermentative bacteria hold great promise for its generation. Here we use the isogenic Escherichia coli K-12 KEIO library to rapidly construct multiple, precise deletions in the E. coli genome to direct the metabolic flux towards hydrogen production. Escherichia coli has three active hydrogenases, and the genes involved in the regulation of the formate hydrogen lyase (FHL) system for synthesizing hydrogen from formate via hydrogenase 3 were also manipulated to enhance hydrogen production. Specifically, we altered regulation of FHL by controlling the regulators HycA and FhlA, removed hydrogen consumption by hydrogenases 1 and 2 via the hyaB and hybC mutations, and re-directed formate metabolism using the fdnG, fdoG, narG, focA, fnr and focB mutations. The result was a 141-fold increase in hydrogen production from formate to create a bacterium (BW25113 hyaB hybC hycA fdoG/pCA24N-FhlA) that produces the largest amount of hydrogen to date and one that achieves the theoretical yield for hydrogen from formate. In addition, the hydrogen yield from glucose was increased by 50%, and there was threefold higher hydrogen production from glucose with this strain.


Suppression of endogenous murine leukemia virus by maternal resistance factor.
Females of the RF and SJL inbred mouse strains transmit to their progeny of both sexes a nonmendelian maternal resistance factor (MRF) able to suppress the expression of endogenous ecotropic murine leukemia virus (E-MuLV). This MRF is demonstrable in crosses with AKR mice by comparing E-MuLV expression in the spleens and thymuses of reciprocal F1 generations. DBA/2 and ST/b mice are MRF negative by these criteria. Neonatal inoculation of E-MuLV-containing spleen extracts gives rise to persistent expression of infectious virus in mice of the MRF- but not the MRF+ strains. However, inoculation of the virus in 30-d-old females of the MRF- strains no longer leads to a state of persistent infection; instead, these females become MRF+ and transmit protection against E-MuLV expression to their progeny by AKR and RF males. The MRF appears to be transmitted to the progeny mainly through the milk, since foster-nursing AKR neonates on RF (but not DBA/2) mothers greatly reduces E-MuLV expression in the progeny. These RF-fostered AKR mice also show a reduced and delayed lymphoma incidence, a finding consistent with the idea that maternally transmitted resistance to E-MuLV expression is the basis for the classic maternal resistance to lymphomagenesis seen in the progeny of RF mothers.


Peel strength of denture liner to PMMA and polyamide: laser versus air-abrasion.
This study investigated the effect of laser parameters and air-abrasion on the peel strength of silicon-based soft denture liner to different denture resins. Specimens (N=180) were prepared out of three different denture base resins (Rodex, cross-linked denture base acrylic resin; Paladent, heat-cured acrylic resin; Deflex, Polyamide resin) (75 mm × 25 mm × 3 mm). A silicon-based soft denture liner (Molloplast B) was applied to the denture resins after the following conditioning methods: a) Air-abrasion (50 µm), b) Er,Cr:YSGG laser (Waterlase MD Turbo, Biolase Technology) at 2 W-20 Hz, c) Er,Cr:YSGG laser at 2 W-30 Hz, d) Er,Cr:YSGG laser at 3 W-20 Hz, e) Er,Cr:YSGG laser at 3 W-30 Hz. Non-conditioned group acted as the control group. Peel test was performed in a universal testing machine. Failure modes were evaluated visually. Data were analyzed using two-way ANOVA and Tukey's test (α=.05). Denture liner tested showed increased peel strength after laser treatment with different parameters (3.9±0.4 - 5.58±0.6 MPa) compared to the control (3.64±0.5 - 4.58±0.5 MPa) and air-abraded groups (3.1±0.6 - 4.46±0.3 MPa), but the results were not statistically significant except for Paladent, with the pretreatment of Er,Cr:YSGG laser at 3 W-20 Hz. Polyamide resin after air-abrasion showed significantly lower peel strength than those of other groups (3.1±0.6 MPa). Heat-cured acrylic resin, PMMA, may benefit from Er,Cr:YSGG laser treatment at 3 W-20 Hz irradiation. Air-abrasion of polyamide resins should be avoided not to impair their peel bond strengths to silicon-based soft denture liners.


Cell line profiling to improve monoclonal antibody production.
Mammalian cell culture performance is influenced by both intrinsic (genetic) and extrinsic (media and process) factors. In this study, intrinsic capacity of various monoclonal antibody-producing Chinese Hamster Ovary (CHO) cell lines was compared by exposing them to the same culture condition. Microarray-based transcriptomics and LC-MS/MS shotgun proteomics technologies were utilized to obtain expression landscape of different cell lines. Specific transcripts and proteins correlating with productivity, growth rate and cell size have been identified. The proteomics analysis results showed a strong correlation between the intracellular protein expression levels of the recombinant DHFR and productivity. In contrast, neither the light chain nor the heavy chain of the recombinant monoclonal antibody showed correlation to productivity. Other top ranked proteins which demonstrated positive correlation to productivity included the adaptor protein complex subunits AP3D1and AP2B2, DNA repair protein DDB1 and the ER translocation complex component, SRPR. The subunits of molecular chaperone T-complex protein 1 and the regulator of mitochondrial one-carbon metabolism MTHFD2 showed negative correlation to productivity. The transcriptomics analysis has identified the regulators of calcium signaling, Tmem20 and Rcan1, as the top ranked genes displaying positive and negative correlation to productivity, respectively. For the second part of the study, the principal component analysis (PCA) was generated to view the underlying global structure of the expression data. A clear division and expression polarity was observed between the two distinct clusters of cell lines, independent of link to productivity or any other traits examined. The primary component of the PCA generated from either transcriptomics or proteomics data displayed a strong correlation to cell size and doubling time, while none of the main principal components showed correlation to productivity. Our findings suggest that productivity is rather a minor feature in the context of global transcriptional or protein expression space.


Determining Clinically Meaningful Thresholds for the Nonarthritic Hip Score in Patients Undergoing Arthroscopy for Femoroacetabular Impingement Syndrome.
The purpose of this study was to improve the interpretability of the Nonarthritic Hip Score (NAHS) by determining the minimal clinically important difference (MCID), patient acceptable symptomatic state (PASS), and substantial clinical benefit (SCB) after hip arthroscopy for femoroacetabular impingement. The secondary aim was to identify variables associated with achievement of the thresholds. Patients who underwent hip arthroscopy for femoroacetabular impingement and completed postoperative questionnaires between August 2019 and March 2020 were included. Patients were excluded if they underwent previous ipsilateral hip surgery, underwent gluteus medius repair, or had a previous hip condition. The MCID, PASS, and SCB thresholds were calculated for the NAHS at minimum 1-, 2-, and 5-year follow-up. Distribution- and anchor-based methods with receiver operating characteristic analysis were used to determine the thresholds. Multivariate logistic regression was performed to determine predictors of achieving the MCID and PASS. The study included 343 hips with an average follow-up period of 48 months. On the basis of the distribution-based approach, the MCID was 8.7 using a method in which the standard deviation of the baseline score was divided by 2. By use of a method in which the standard deviation of the change score was divided by 2, MCID scores of 9.1, 8.3, and 12.6 resulted at a minimum of 1, 2, and 5 years, respectively. The PASS thresholds for these time points were 81.9, 85.6, and 81.9. The absolute SCB thresholds were 91.9, 94.4, and 93.1 and the change score thresholds were 30.6, 24.4, and 29.3 for a minimum of 1, 2, and 5 years, respectively. The preoperative NAHS was positively associated with achievement of the PASS and inversely related to achievement of the MCID. This study provides important clinical thresholds for the NAHS. These thresholds were determined for minimum 1-, 2-, and 5-year time points. The MCID was determined as 8.7, the PASS ranged between 81.9 and 85.6, and the absolute SCB value ranged from 91.9 to 94.4. The preoperative NAHS was found to be positively associated with achievement of the PASS and inversely related to achievement of the MCID. Level IV, retrospective case series.


Clot friction variation with fibrin content; implications for resistance to thrombectomy.
Despite significant advancements in the procedural efficacy of mechanical thrombectomy in patients with ischemic stroke in recent years, there still remains a portion of the population that does not achieve good recanalization. The reasons for this may be varied. We hypothesized that static friction between the clot and the vessel, or catheter wall might contribute to the difficulty in removing the clot. To determine if there is a relationship between clot composition and the resistance to sliding (friction) which might contribute to resistance to clot removal. As clot composition can vary significantly, we investigated five different types of clot in order to measure their respective frictional properties. To do this, a custom-made testing apparatus was created, consisting of various replaceable low-friction surfaces on which the clots could be placed. The surface was then gradually tilted until the clots began to slide; the angle at which this occurred is related to the coefficient of friction of the clots. The experiment was repeated on a bovine aortic surface in order to confirm the results. We found that fibrin-rich clots (<20% red blood cell content) have a significantly higher coefficient of friction than clots with a red blood cell content >20%. This result was confirmed by repeating the experiment on a bovine aortic surface as a representation of the interaction between clots and the arterial wall. The friction properties of clots were found to be related to the content ratio of fibrin to red blood cells. Future imaging techniques that could show fibrin and red blood cell content might help us to predict the 'stickiness' of a clot.


On-site treatment of domestic wastewater using a small-scale horizontal subsurface flow constructed wetland.
A small-scale horizontal subsurface flow constructed wetland, located in North Greece, was designed and constructed to treat wastewater from a single-family residence. A three-year monitoring program was undertaken to evaluate the performance of this system. The monitoring campaigns were organized every 7 days. Water quality samples were collected at the inlet, at intermediate points (i.e. at the end of each treatment stage) and at the outlet of the system. Temperature, electrical conductivity, pH and DO were measured in-situ with the use of appropriate instruments at the same points of water sample collection. Water samples were analyzed for BOD, COD, TKN, ammonia, nitrate, nitrite, total phosphorus (TP), ortho-phosphate (OP), total suspended solids (TSS) and total coliforms (TC). Mean removal efficiencies for the monitoring period were: 86.5% for BOD, 84.6% for COD, 83.7% for TKN, 82.2% for ammonia, 63.1% for OP, 63.3% for TP, 79.3% for TSS and 99.9% for TC. Furthermore, based on statistical testing, TKN, ammonia and TP removal efficiencies showed dependence on temperature. The paper presents facility description, study details and monitoring results. The study shows that the use of constructed wetlands in wastewater treatment is a good option for single-family residences in rural areas.


The role of dobutamine stress cardiovascular magnetic resonance in the clinical management of patients with suspected and known coronary artery disease.
Recent studies have demonstrated the consistently high diagnostic and prognostic value of dobutamine stress cardiovascular magnetic resonance (DCMR). The value of DCMR for clinical decision making still needs to be defined. Hence, the purpose of this study was to assess the utility of DCMR regarding clinical management of patients with suspected and known coronary artery disease (CAD) in a routine setting. We prospectively performed a standard DCMR examination in 1532 consecutive patients with suspected and known CAD. Patients were stratified according to the results of DCMR: DCMR-positive patients were recommended to undergo invasive coronary angiography and DCMR-negative patients received optimal medical treatment. Of 609 (40%) DCMR-positive patients coronary angiography was performed in 478 (78%) within 90 days. In 409 of these patients significant coronary stenoses ≥ 50% were present (positive predictive value 86%). Of 923 (60%) DCMR-negative patients 833 (90%) received optimal medical therapy. During a mean follow-up period of 2.1 ± 0.8 years (median: 2.1 years, interquartile range 1.5 to 2.7 years) 8 DCMR-negative patients (0.96%) sustained a cardiac event.In 131 DCMR-positive patients who did not undergo invasive angiography, 20 patients (15%) suffered cardiac events. In 90 DCMR-negative patients (10%) invasive angiography was performed within 2 years (range 0.01 to 2.0 years) with 56 patients having coronary stenoses ≥ 50%. In a routine setting DCMR proved a useful arbiter for clinical decision making and exhibited high utility for stratification and clinical management of patients with suspected and known CAD.


PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection.
The virulence factor IpgD, delivered into nonphagocytic cells by the type III secretion system of the pathogen Shigella flexneri, is a phosphoinositide 4-phosphatase generating phosphatidylinositol 5 monophosphate (PtdIns5P). We show that PtdIns5P is rapidly produced and concentrated at the entry foci of the bacteria, where it colocalises with phosphorylated Akt during the first steps of infection. Moreover, S. flexneri-induced phosphorylation of host cell Akt and its targets specifically requires IpgD. Ectopic expression of IpgD in various cell types, but not of its inactive mutant, or addition of short-chain penetrating PtdIns5P is sufficient to induce Akt phosphorylation. Conversely, sequestration of PtdIns5P or reduction of its level strongly decreases Akt phosphorylation in infected cells or in IpgD-expressing cells. Accordingly, IpgD and PtdIns5P production specifically activates a class IA PI 3-kinase via a mechanism involving tyrosine phosphorylations. Thus, S. flexneri parasitism is shedding light onto a new mechanism of PI 3-kinase/Akt activation via PtdIns5P production that plays an important role in host cell responses such as survival.


The challenge of democratic patient representation: Understanding the representation work of patient organizations through methodological triangulation.
Increasingly, patient organizations (POs) play a role in health policy making. Their involvement is expected to contribute to the democratization of decision making. It is therefore important to study this contribution. Scholars hardly draw on representation theory for this. Yet exploring POs as a case of representation is crucial to better understand how POs add to democratizing health policy. Our study departs from the assumption that POs contribute to the democratization of health policy in case they perform democratic representation. We studied the representation work of 33 POs covering rare diseases in Austria, Germany and the Netherlands by conducting a thematic analysis of document and interview data collected in 2016. The results show that POs work on turning their representative efforts into democratic representation by applying different mechanisms of authorization and accountability. Yet because of difficulties that come along with these mechanisms, POs differ regarding their contribution to democratizing health policy. Our findings further suggest that not all means of authorization and accountability work out in representation practice as hoped for in representation theory. We therefore recommend policy makers to pay attention to what means of authorization and accountability POs use for their representation work.


Anomaly detection based on sensor data in petroleum industry applications.
Anomaly detection is the problem of finding patterns in data that do not conform to an a priori expected behavior. This is related to the problem in which some samples are distant, in terms of a given metric, from the rest of the dataset, where these anomalous samples are indicated as outliers. Anomaly detection has recently attracted the attention of the research community, because of its relevance in real-world applications, like intrusion detection, fraud detection, fault detection and system health monitoring, among many others. Anomalies themselves can have a positive or negative nature, depending on their context and interpretation. However, in either case, it is important for decision makers to be able to detect them in order to take appropriate actions. The petroleum industry is one of the application contexts where these problems are present. The correct detection of such types of unusual information empowers the decision maker with the capacity to act on the system in order to correctly avoid, correct or react to the situations associated with them. In that application context, heavy extraction machines for pumping and generation operations, like turbomachines, are intensively monitored by hundreds of sensors each that send measurements with a high frequency for damage prevention. In this paper, we propose a combination of yet another segmentation algorithm (YASA), a novel fast and high quality segmentation algorithm, with a one-class support vector machine approach for efficient anomaly detection in turbomachines. The proposal is meant for dealing with the aforementioned task and to cope with the lack of labeled training data. As a result, we perform a series of empirical studies comparing our approach to other methods applied to benchmark problems and a real-life application related to oil platform turbomachinery anomaly detection.


Cluster headache-like attack as an opening symptom of a unilateral infarction of the cervical cord: persistent anaesthesia and dysaesthesia to cold stimuli.
A 54 year old man experienced excruciating left retro-orbital pain with lacrimation and redness of the eye representative of a cluster headache attack. This was followed by left hemiparesis with plegia of the lower limb and left Horner's syndrome. Five days later the hemiparesis recovered while the patient developed hypoanaesthesia to cold stimuli that evoked painful burning dysaesthesia on the right side below the C4 level. MRI disclosed a discrete infarct in the left lateral aspect of the cord at C2 level concomitant to a left vertebral artery thrombosis. This limited infarct and the clinical symptoms suggest a hypoperfusion in the peripheral arterial system of the left hemicord, supplied both by the anterior and posterior spinal arteries. Cluster headache-like attack and persistent dysaesthesia to cold stimuli are discussed respectively in view of the central sympathetic involvement and partial spinothalamic system dysfunction.


Interactions between fused, a segment-polarity gene in Drosophila, and other segmentation genes.
Fused (fu) is a segment polarity gene whose product is maternally required in the posterior part of each segment. To define further the role of fused and determine how it interacts with other segmentation genes, we examined the phenotypes obtained by combining fused with mutations of pair rule, homeotic and other segment polarity loci. When it was possible, we also looked at the distribution of corresponding proteins in fused mutant embryos. We observed that fused-naked (fu;nkd) double mutant embryos display a phenotypic suppression of simple mutant phenotypes: both naked cuticle and denticle belts, which would normally have been deleted by one of the two mutants alone, were restored. In fused mutant embryos, engrailed (en) and wingless (wg) expression was normal until germ band extension, but partially and completely disappeared respectively during germ band retraction. In the fu;nkd double mutant embryo, en was expressed as in nkd mutant at germ band extension, but later this expression was restricted and became normal at germ band retraction. On the contrary, wg expression disappeared as in fu simple mutant embryos. We conclude that the requirements for fused, naked and wingless activities for normal segmental patterning are not absolute, and propose mechanisms by which these genes interact to specify anterior and posterior cell fates.


Minocycline ameliorates lung and liver dysfunction in a rodent model of hemorrhagic shock/resuscitation plus abdominal compartment syndrome.
We sought to elucidate whether minocycline, a broad-spectrum tetracycline antibiotic with potent anti-inflammation capacity, could mitigate inflammatory response and organ dysfunction in the lungs and liver induced by hemorrhagic shock/resuscitation (HS) plus abdominal compartment syndrome (ACS). Adult male rats were randomized to receive HS plus ACS or HS plus ACS plus minocycline (denoted as the HS/A and HS/A-M group, respectively; n = 12). Sham-instrumentation groups were employed to serve as the controls. Hemorrhagic shock/resuscitation was induced by blood drawing (mean arterial pressure: 40-45 mm Hg for 60 min) followed by shed blood/saline mixture reinfusion. Subsequently, intra-abdominal pressure (IAP) was increased to 25 mm Hg by injecting air into the preplaced intraperitoneal latex balloon to induce ACS. Minocycline (20 mg/kg) was intravenously administered immediately after resuscitation. IAP was maintained at 25 mm Hg for 6 h. Then, all rats were euthanized. The levels of polymorphonuclear leukocyte infiltration, the wet/dry weight ratio, and the concentrations of inflammatory molecules (e.g., chemokine, cytokine, and prostaglandin E2) in lung and liver tissues of the HS/A group were significantly higher than those of the HS/A-M groups (all P < 0.05). Moreover, the levels of lung dysfunction (assayed by arterial blood gas) and liver dysfunction (assayed by plasma concentrations of bilirubin, aspartate aminotransferase, and alaninine aminotransferase) of the HS/A group were significantly higher than those of the HS/A-M group (all P < 0.05). Minocycline ameliorates inflammatory response and organ dysfunction in the lungs and liver induced by hemorrhagic shock/resuscitation plus abdominal compartment syndrome.


Ultra-low voltage electrowetting using graphite surfaces.
The control of wetting behaviour underpins a variety of important applications from lubrication to microdroplet manipulation. Electrowetting is a powerful method to achieve external wetting control, by exploiting the potential-dependence of the liquid contact angle with respect to a solid substrate. Addition of a dielectric film to the surface of the substrate, which insulates the electrode from the liquid thereby suppressing electrolysis, has led to technological advances such as variable focal-length liquid lenses, electronic paper and the actuation of droplets in lab-on-a-chip devices. The presence of the dielectric, however, necessitates the use of large bias voltages (frequently in the 10-100 V range). Here we describe a simple, dielectric-free approach to electrowetting using the basal plane of graphite as the conducting substrate: unprecedented changes in contact angle for ultra-low voltages are seen below the electrolysis threshold (50° with 1 V for a droplet in air, and 100° with 1.5 V for a droplet immersed in hexadecane), which are shown to be reproducible, stable over 100 s of cycles and free of hysteresis. Our results dispel conventional wisdom that reversible, hysteresis-free electrowetting can only be achieved on solid substrates with the use of a dielectric. This work paves the way for the development of a new generation of efficient electrowetting devices using advanced materials such as graphene and monolayer MoS2.


Matrix-bound phosphine in sediments from Lake Illawarra, New South Wales, Australia.
Matrix-bound phosphine (MBP) has been measured in sediment from two cores in Lake Illawarra on the south east coast of Australia. The sediments were also dated in the upper layers. MBP concentrations found range from 142 to 1813 ng kg(-1), dw (dry weight of sediment) with some values being amongst the highest ever measured. Values of MBP in deeper sediments were higher than for near surface samples, but the patterns with depth were not consistent. Strong correlations were noted between MBP and organic phosphorus (OP, r>0.8) and with total phosphorus (TP, r>0.7), but only moderate correlations were found with organic carbon (OC, r>0.5). No correlations were found between MBP concentrations and the age of the sediments. It was confirmed that high MBP concentrations are indicative of a phosphorus rich environment. The results tend to support the premise that MBP is generated by microbial attack on OP under anaerobic conditions.


Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy.
Cerebral ischemia is the leading cause of preventable death in cases of major trauma with severe traumatic brain injury (TBI). Intracranial pressure (ICP) control and cerebral perfusion pressure (CPP) manipulation have significantly reduced the mortality but not the morbidity rate in these patients. In this study, the authors describe their 5-year experience with brain tissue oxygen (PbtO(2)) monitoring, and the effect of a brain tissue oxygen-directed critical care guide (PbtO(2)-CCG) on the 6-month clinical outcome (based on the 6-month Glasgow Outcome Scale score) in patients with TBIs. One hundred thirty-nine patients admitted to Creighton University Medical Center with major traumatic injuries (Injury Severity Scale [ISS] scores >or= 16) and TBI underwent prospective evaluation. All patients were treated with a PbtO(2)-CCG to maintain a brain oxygen level > 20 mm Hg, and control ICP < 20 mm Hg. The role of demographic, clinical, and imaging parameters in the identification of patients at risk for cerebral hypooxygenation and the influence of hypooxygenation on clinical outcome were recorded. Outcomes were compared with those in a historical ICP/CPP patient cohort. Subgroup analysis of severe TBI was performed and compared to data reported in the Traumatic Coma Data Bank. The majority of injuries were sustained in motor vehicle crashes (63%), and diffuse brain injury was the most common abnormality (58%). Mechanism of injury, severity of TBI, pathological entity, neuroimaging results, and trauma indices were not predictive of ischemia. Factors affecting death included gunshot injury, poor trauma indices, subarachnoid hemorrhage, and coma. After standard resuscitation, 65% of patients had an initially low PbtO(2). Data are presented as means +/- SDs. Treatment with the PbtO(2)-CCG resulted in a 44% improvement in mean PbtO(2) (16.21 +/- 12.30 vs 23.65 +/- 14.40 mm Hg; p < 0.001), control of ICP (mean 12.76 +/- 6.42 mm Hg), and the maintenance of CPP (mean 76.13 +/- 15.37 mm Hg). Persistently low cerebral oxygenation was seen in 37% of patients at 2 hours, 31% at 24 hours, and 18% at 48 hours of treatment. Thus elevated ICP and a persistent low PbtO(2) after 2 hours represented increasing odds of death (OR 14.3 at 48 hours). Survivors and patients with good outcomes generally had significantly higher mean daily PbtO(2) and CPP values compared to nonsurvivors. Polytrauma, associated with higher ISS scores, presented an increased risk of vegetative outcome (OR 9.0). Compared to the ICP/CPP cohort, the mean Glasgow Outcome Scale score at 6 months in patients treated with PbtO(2)-CCG was higher (3.55 +/- 1.75 vs 2.71 +/- 1.65, p < 0.01; OR for good outcome 2.09, 95% CI 1.031-4.24) as was the reduction in mortality rate (25.9 vs 41.50%; relative risk reduction 37%), despite higher ISS scores in the PbtO(2) group (31.6 +/- 13.4 vs 27.1 +/- 8.9; p < 0.05). Subgroup analysis of severe closed TBI revealed a significant relative risk reduction in mortality rate of 37-51% compared with the Traumatic Coma Data Bank data, and an increased OR for good outcome especially in patients with diffuse brain injury without mass lesions (OR 4.9, 95% CI 2.9-8.4). The prevention and aggressive treatment of cerebral hypooxygenation and control of ICP with a PbtO(2)-directed protocol reduced the mortality rate after TBI in major trauma, but more importantly, resulted in improved 6-month clinical outcomes over the standard ICP/CPP-directed therapy at the authors' institution.


Diverse pathways of epithelial mesenchymal transition related with cancer progression and metastasis and potential effects of endocrine disrupting chemicals on epithelial mesenchymal transition process.
Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with normal functions of natural hormones in the body, leading to a disruption of the endocrine system. Specifically, EDCs have the potential to cause formation of several hormone-dependent cancers, including breast, ovarian, and prostate cancers. Epithelial mesenchymal transition (EMT) process by which epithelial cells lose their cell polarity and cell-cell adhesion and acquire mesenchymal phenotype is closely associated with malignant transformation and the initiation of cancer metastasis. As a key epithelial marker responsible for adherens junction, E-cadherin enables the cells to maintain epithelial phenotypes. EMT event is induced by E-cadherin loss which can be carried out by many transcription factors (TFs), including Snail, Slug, ZEB1, ZEB2, Kruppel-like factor 8 (KLF8), and Twist. N-cadherin, fibronectin, and vimentin are mesenchymal markers needed for cellular migration. The EMT process is regulated by several signaling pathways mediated by transforming growth factor β (TGF-β), Wnt-β-catenin, Notch, Hedgehog, and receptor tyrosine kinases. In the present article, we reviewed the current understanding of cancer progression effects of synthetic chemical EDCs such as bisphenol A (BPA), phthalates, tetrachlorodibenzo-p-dioxin (TCDD), and triclosan by focusing their roles in the EMT process. Collectively, the majority of previous studies revealed that BPA, phthalates, TCDD, and triclosan have the potential to induce cancer metastasis through regulating EMT markers and migration via several signaling pathways associated with the EMT program. Therefore, it is considered that the exposure to these EDCs can increase the risk aggravating the disease for the patients suffering cancer and that more regulations about the use of these EDCs are needed.


Treatment for amphetamine withdrawal.
Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine withdrawal. Amineptine showed reduction in discontinuation rates and improvement in clinical presentation compared to placebo, but had no effect on reducing withdrawal symptoms or craving. In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. The benefits of mirtazapine as a withdrawal agent are less clear based on findings from two randomised controlled trials: one report showed improvements in amphetamine withdrawal symptoms over placebo; a second report showed no differences in withdrawal symptoms compared to placebo. Further potential treatment studies should examine medications that increase central nervous system activity involving dopamine, norepinephrine and/or serotonin neurotransmitters, including mirtazapine.


Awareness, knowledge, and practice for hepatitis B infection in Southeast Asia: a cross-sectional study.
The prevalence of hepatitis B virus (HBV) infection in Southeast Asia is high. Awareness and early detection are essential for timely prevention and treatment. We examined the awareness of, knowledge about, practices and views on treatment for HBV infection in Southeast Asia. A cross-sectional survey was conducted from December 2016 to February 2017 among individuals from six nations in Southeast Asia-Myanmar, Thailand, Vietnam, Cambodia, the Philippines, and Singapore. The study population comprised healthcare and non-healthcare personnel. In total, 799 healthcare personnel and 1079 non-healthcare personnel completed an online survey. The prevalence of the awareness of their own HBV infection status and risk of this regionally endemic infection was 85.6% (684/799) among healthcare personnel and 54.0% (583/1079) among non-healthcare personnel. Similarly, 85.9% of healthcare personnel and 45.5% of non-healthcare personnel had good knowledge about disease transmission, complications, and the need for treatment, and 76.6% of healthcare personnel and 39.8% of non-healthcare personnel followed good HBV infection-prevention practices. Overall, 90.6% found the idea of treatment acceptable. Awareness had a significant impact on both knowledge and practice scores among both healthcare personnel and non-healthcare personnel (p < 0.01) but without statistically significant differences in treatment acceptance between the two groups (p = 0.61). Awareness of HBV infection was relatively low among non-healthcare personnel in Southeast Asian populations. The provision of additional hepatitis B awareness campaigns is crucial to eliminating viral hepatitis in the region.


Impact of age on acute post-TBI neuropathology in mice expressing humanized tau: a Chronic Effects of Neurotrauma Consortium Study.
We hypothesized that polypathology is more severe in older than younger mice during the acute phase following repetitive mild traumatic brain injury (r-mTBI). Young and aged male and female mice transgenic for human tau (hTau) were exposed to r-mTBI or a sham procedure. Twenty-four hours post-last injury, mouse brain tissue was immunostained for alterations in astrogliosis, microgliosis, tau pathology, and axonal injury. Quantitative analysis revealed a greater percent distribution of glial fibrillary acid protein and Iba-1 reactivity in the brains of all mice exposed to r-mTBI compared to sham controls. With respect to axonal injury, the number of amyloid precursor protein-positive profiles was increased in young vs aged mice post r-mTBI. An increase in tau immunoreactivity was found in young and aged injured male hTau mice. We report the first evidence in our model that r-mTBI precipitates a complex sequelae of events in aged vs young hTau mice at an acute time point, typified by an increase in phosphorylated tau and astroglisosis, and a diminished microgliosis response and axonal injury in aged mice. These findings suggest differential age-dependent effects in TBI pathobiology.


Fibrinogen is degraded and internalized during incubation with neutrophils, and fibrinogen products localize to electron lucent vesicles.
A biologically relevant relationship exists between neutrophils and coagulation processes. Several studies have focused on the ability of neutrophil proteases (both intracellular and membrane-associated) to degrade fibrinogen. The present study investigates the events following the interaction of activated neutrophils with soluble fibrinogen. During incubation of PMA-stimulated neutrophils with fibrinogen at 37 degrees C, fibrinogenolysis occurred, and degraded fibrinogen became associated with the neutrophil. Immunoelectron microscopy identified these fibrinogen products to be located within electron lucent vesicles, and not on the surface of the cell, suggesting that they are internalized. Although a specific interaction between fibrinogen and the neutrophil membrane might assist uptake, in the presence of physiological concentrations of fibrinogen, internalization occurred largely via a non-specific pinocytic process. Studies at low temperature revealed that both intact and degraded forms of fibrinogen can associate with neutrophils. The fibrinogen products detected intracellularly in experiments performed at 37 degrees C might represent uptake of degraded as well as intact forms of fibrinogen, the latter being rapidly degraded intracellularly. This route of fibrinogenolysis contributes minimally to the overall extent of the degradation process, the majority occurring extracellularly. Neutrophils thus possess a proteolytic mechanism for preventing accumulation of surface ligand, perhaps allowing them to evade the immunomodulatory effects of such ligands during inflammation.


Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters.
Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts.


Biceps detachment decreases joint damage in a rotator cuff tear rat model.
Pathology in the long head of the biceps tendon often occurs in patients with rotator cuff tears. Arthroscopic tenotomy is the most common treatment. However, the role of the long head of the biceps at the shoulder and the consequences of surgical detachment on the remaining shoulder structures remain unknown. We hypothesized that detachment of the long head of the biceps, in the presence of supraspinatus and infraspinatus tears, would decrease shoulder function and decrease mechanical and histologic properties of both the subscapularis tendon and the glenoid articular cartilage. We detached the supraspinatus and infraspinatus or the supraspinatus, infraspinatus, and long head of the biceps after 4 weeks of overuse in a rat model. Animals were gradually returned to overuse activity after detachment. At 8 weeks, the subscapularis and glenoid cartilage biomechanical and histologic properties were evaluated and compared. The supraspinatus, infraspinatus, and long head of the biceps group had a decreased change in braking and vertical force. [corrected]. This group also had an increased upper and lower subscapularis modulus but without any differences in glenoid cartilage modulus. Finally, this group had a significantly lower cell density in both the upper and lower subscapularis tendons, although cartilage histology was not different. Detachment of the long head of the biceps tendon in the presence of a posterior-superior cuff tear resulted in improved shoulder function and less joint damage in this animal model. This study provides evidence in an animal model that supports the use of tenotomy for the management of long head of the biceps pathology in the presence of a two-tendon cuff tear. However, long-term clinical trials are required.


Use of platelet-rich plasma for the treatment of refractory jumper's knee.
The aim of this study was to evaluate the efficacy of multiple platelet-rich plasma (PRP) injections on the healing of chronic refractory patellar tendinopathy after previous classical treatments have failed. We treated 15 patients affected by chronic jumper's knee, who had failed previous nonsurgical or surgical treatments, with multiple PRP injections and physiotherapy. We also compared the clinical outcome with a homogeneous group of 16 patients primarily treated exclusively with the physiotherapy approach. Multiple PRP injections were performed on three occasions two weeks apart into the site of patellar tendinopathy. Tegner, EQ VAS and pain level were used for clinical evaluation before, at the end of the treatment and at six months follow-up. Complications, functional recovery and patient satisfaction were also recorded. A statistically significant improvement in all scores was observed at the end of the PRP injections in patients with chronic refractory patellar tendinopathy and a further improvement was noted at six months, after physiotherapy was added. Moreover, comparable results were obtained with respect to the less severe cases in the EQ VAS score and pain level evaluation, as in time to recover and patient satisfaction, with an even higher improvement in the sport activity level achieved in the PRP group. The clinical results are encouraging, indicating that PRP injections have the potential to promote the achievement of a satisfactory clinical outcome, even in difficult cases with chronic refractory tendinopathy after previous classical treatments have failed.


Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol.
The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings. The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics. NCT01732250 and 2012-004819-31; Pre-results.


Test anxiety in UK schoolchildren: prevalence and demographic patterns.
Despite a large body of international literature concerning the antecedents, correlates of and treatments for test anxiety, there has been little research until recently using samples of students drawn from the UK. There is a need to establish some basic normative data for test anxiety scores in this population of students, in order to establish whether international research findings may generalize to UK schoolchildren. To collect some exploratory data regarding test anxiety scores in a sample of UK schoolchildren, along with socio-demographic variables identified in the existing literature as theoretically significant sources of individual and group differences in test anxiety scores. Key Stage 4 students (1348): 690 students in the Year 10 cohort and 658 students in the Year 11 cohort, drawn from seven secondary schools in the North of the UK. Data on test anxiety were collected using a self-report questionnaire, the Test Anxiety Inventory (Spielberger, 1980) and additional demographic variables through the Student Profile Questionnaire. The factor structure of the Test Anxiety Inventory was explored using principal components analysis and multiple regression analysis used to predict variance in self-reported test anxiety scores from individual and group variables. The principal components analysis extracted two factors, worry and emotionality, in line with theoretical predictions. Gender, ethnic and socio-economic background were identified as significant predictors of variance in test anxiety scores in this dataset. Whether English was an additional, or native, language of students did not predict variance in test anxiety scores and year group was identified as a predictor of emotionality scores only. Variance in the test anxiety scores of Key Stage 4 students can be predicted from a number of socio-demographic variables. Further research is now required to assess the implications for assessment performance, examination arrangements and appropriateness of using a North American measure of test anxiety in a UK context.


Play in orphanages.
This paper attempts to validate the programme of structured play lasting 90 minutes a day, for use in orphanages, to check if it can be replicated in other orphanages, with similar results. A 2-week workshop on the structured play scheme was conducted at the Missionaries of Charity Orphanage in Delhi, the venue of the original project. 15 MOC sisters from 6 centers attended the workshop. The authors selected the MOC orphanage at Chandigarh to track the benefits of the programme. The development quotient of all the residents between the ages of 6 months - 3 years was assessed by a pediatric-clinical-psychologist using the Development Assessment Scale for Indian Infants (DAS II) scale. A reassessment of all these children was done again 3 months after initiating the programme of structured play here. The mean motor and mental scores at the orphanage in Chandigarh before the start of the intervention were 57.9 and 58.2 respectively. Post intervention assessments showed a rise of 23 points in both the scores. The development of children in orphanages rises dramatically after initiating a programme of play. The pre-intervention development scores is similar to that in a pilot study and the benefits after play was also similar. The play programme can be easily replicated in other orphanages with similar results.


Classic reaction kinetics can explain complex patterns of antibiotic action.
Finding optimal dosing strategies for treating bacterial infections is extremely difficult, and improving therapy requires costly and time-intensive experiments. To date, an incomplete mechanistic understanding of drug effects has limited our ability to make accurate quantitative predictions of drug-mediated bacterial killing and impeded the rational design of antibiotic treatment strategies. Three poorly understood phenomena complicate predictions of antibiotic activity: post-antibiotic growth suppression, density-dependent antibiotic effects, and persister cell formation. We show that chemical binding kinetics alone are sufficient to explain these three phenomena, using single-cell data and time-kill curves of Escherichia coli and Vibrio cholerae exposed to a variety of antibiotics in combination with a theoretical model that links chemical reaction kinetics to bacterial population biology. Our model reproduces existing observations, has a high predictive power across different experimental setups (R(2) = 0.86), and makes several testable predictions, which we verified in new experiments and by analyzing published data from a clinical trial on tuberculosis therapy. Although a variety of biological mechanisms have previously been invoked to explain post-antibiotic growth suppression, density-dependent antibiotic effects, and especially persister cell formation, our findings reveal that a simple model that considers only binding kinetics provides a parsimonious and unifying explanation for these three complex, phenotypically distinct behaviours. Current antibiotic and other chemotherapeutic regimens are often based on trial and error or expert opinion. Our "chemical reaction kinetics"-based approach may inform new strategies, which are based on rational design.


Stroke in Devon: knowledge was good, but action was poor.
Effective implementation of early treatment strategies for stroke requires prompt admission to hospital. There are several reasons for delayed admission. Good awareness should facilitate early admission. We identified local targets for education. Four groups, each of 40 people, completed questionnaires to determine their knowledge of stroke symptoms and risk factors, and the action they took or would take in the event of a stroke. The groups were: patients with a diagnosis of stroke or TIA (within 48 hrs of admission); patients at risk of stroke; the general population; and nurses. Forty per cent of stroke patients identified their stroke. Median time from onset of symptoms to seeking medical help was 30 minutes. Medical help was sought by the patient themselves in only 15% of cases. In 80% of cases the GP was called rather than an ambulance. Of the at risk group, 93% were able to list at least one symptom of acute stroke, as were 88% of the general population. An ambulance would be called by 73% of the at risk group in the event of a stroke. Patients with self reported risk factors for stroke were largely unaware of their increased risk. Only 7.5% of at risk patients acquired their stroke information from the medical profession. Public knowledge about stroke is good. However, stroke patients access acute services poorly. At risk patients have limited awareness of their increased risk. A campaign should target people at risk, reinforcing the diagnosis of stroke and access to medical services.


The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients.
Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined. Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment. Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests. A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.


Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection.
Chagas' disease is caused by infection with the parasite Trypanosoma cruzi. We report that infected, but not uninfected, human endothelial cells (ECs) released thromboxane A(2) (TXA(2)). Physical chromatography and liquid chromatography-tandem mass spectrometry revealed that TXA(2) is the predominant eicosanoid present in all life stages of T. cruzi. Parasite-derived TXA(2) accounts for up to 90% of the circulating levels of TXA(2) in infected wild-type mice, and perturbs host physiology. Mice in which the gene for the TXA(2) receptor (TP) has been deleted, exhibited higher mortality and more severe cardiac pathology and parasitism (fourfold) than WT mice after infection. Conversely, deletion of the TXA(2) synthase gene had no effect on survival or disease severity. TP expression on somatic cells, but not cells involved in either acquired or innate immunity, was the primary determinant of disease progression. The higher intracellular parasitism observed in TP-null ECs was ablated upon restoration of TP expression. We conclude that the host response to parasite-derived TXA(2) in T. cruzi infection is possibly an important determinant of mortality and parasitism. A deeper understanding of the role of TXA(2) may result in novel therapeutic targets for a disease with limited treatment options.


Complete obstruction of the gastric antrum in children following acid ingestion.
We report on two children who experienced delayed complete obstruction of the gastric antrum following concentrated acid ingestion. Both patients required initial tube gastrostomy and subsequent antrectomy with intestinal reconstruction. Unlike the more common alkaline corrosives, ingested acids tend to spare the esophagus and gastric fundus. While gastric perforation and vascular collapse may occur immediately following overwhelming acid ingestion, the more common course is chronic gastric antral inflammation with subsequent fibrosis and, in some cases, complete stricture. Delayed surgical reconstruction is recommended to permit the acute inflammation and edema to subside.


Granulomatous reaction to silicone injection.
The use of liquid injectable silicone for soft tissue augmentation is controversial. Proponents of its use consider it safe when highly purified medical-grade product is employed appropriately by well-trained and experienced physicians, whereas opponents believe complications from silicone injections are inherently inevitable and unpredictable and that they outweigh the benefits. One of the feared complications is granuloma formation. In this article, the authors report two cases of granulomatous nodules from silicone injections and present the histological features. These cases highlight the need for continued vigilance among clinicians about this complication and the importance not only of careful selection of filler products, but also of patients knowing the credentials of their injection practitioners.


Applying a correction procedure to the prevalence estimates of overweight and obesity in the German part of the HBSC study.
Prevalence rates for overweight and obesity based on self-reported height and weight are underestimated, whereas the prevalence rate for underweight is slightly overestimated. Therefore a correction is needed. Aim of this study is to apply correction procedures to the prevalence rates developed on basis of (self-reported and measured) data from the representative German National Health Interview and Examination Survey for Children and Adolescents (KiGGS) to (self-reported) data from the German Health Behaviour in School Aged Children (HBSC) study to determine whether correction leads to higher prevalence estimates of overweight and obesity as well as lower prevalence rates for underweight. BMI classifications based on self-reported and measured height and weight from a subsample of the KiGGS study (2,565 adolescents aged 11-15) were used to estimate two different correction formulas. The first and the second correction function are described. Furthermore, the both formulas were applied to the prevalence rates from the HBSC study (7,274 adolescents aged 11-15) which are based on self-reports collected via self-administered questionnaires. After applying the first correction function to self-reported data of the HBSC study, the prevalence rates of overweight and obesity increased from 5.5% to 7.8% (compared to 10.4% in the KiGGS study) and 2.7% to 3.8% (compared to 7.8% in the KiGGS study), respectively, whereas the corrected prevalence rates of underweight and severe underweight decreased from 8.0% to 6.7% (compared to 5.7% in the KiGGS study) and from 5.5% to 3.3% (compared to 2.4% in the KiGGS study), respectively. Application of the second correction function, which additionally considers body image, led to further slight corrections with an increase of the prevalence rates for overweight to 7.9% and for obese to 3.9%. Subjective BMI can be used to determine the prevalence of overweight and obesity among children and adolescents. Where there is evidence of bias, the prevalence estimates should be corrected using conditional probabilities that link measured and subjectively assessed BMI from a representative validation study. These corrections may be improved further by considering body image as an additional influential factor.


Patient-specific cardiac phantom for clinical training and preprocedure surgical planning.
Minimally invasive mitral valve repair procedures including MitraClip® are becoming increasingly common. For cases of complex or diseased anatomy, clinicians may benefit from using a patient-specific cardiac phantom for training, surgical planning, and the validation of devices or techniques. An imaging compatible cardiac phantom was developed to simulate a MitraClip® procedure. The phantom contained a patient-specific cardiac model manufactured using tissue mimicking materials. To evaluate accuracy, the patient-specific model was imaged using computed tomography (CT), segmented, and the resulting point cloud dataset was compared using absolute distance to the original patient data. The result, when comparing the molded model point cloud to the original dataset, resulted in a maximum Euclidean distance error of 7.7 mm, an average error of 0.98 mm, and a standard deviation of 0.91 mm. The phantom was validated using a MitraClip® device to ensure anatomical features and tools are identifiable under image guidance. Patient-specific cardiac phantoms may allow for surgical complications to be accounted for preoperative planning. The information gained by clinicians involved in planning and performing the procedure should lead to shorter procedural times and better outcomes for patients.


Lateral Canthal Tendon Disinsertion: Clinical Characteristics and Anatomical Correlates.
To highlight features of lateral canthal tendon disinsertion (LCTD), provide an algorithm for systematic assessment, and describe the anatomic genesis of signs and symptoms. Retrospective case series of consecutive patients with lateral canthal tendon disinsertion, who underwent lateral canthal tendon fixation by a single surgeon (DTT) between 2004 and 2011. One hundred and seventeen eyes in 90 patients underwent lateral canthal tendon fixation. Average age was 69.3 ± 17.9 years. Twenty-three percentage of eyes had undergone lower eyelid blepharoplasty and 52% had undergone lateral canthal tightening; 35% had no previous periocular surgery. Patients with purely involutional lateral canthal tendon disinsertion were significantly older (76.1 ± 7.8 years of age; p < 0.03). Six key features associated with lateral canthal tendon disinsertion were identified. On static evaluation: 1) a blunted or vertically displaced lateral canthal angle; 2) a narrow horizontal fissure with reduced temporal scleral triangle; and 3) pseudo eyelid retraction. On dynamic evaluation with attempted closure: 4) medial and inferior movement of the lateral commissure; 5) incomplete apposition of the eyelid margins in the absence of anterior lamellar shortage; and 6) temporal eyelid imbrication. Improved blink dynamics with manual lateral canthal tendon complex repositioning ("the thumb test") predicted a favorable outcome with surgical tightening in 95.7% of cases. Lateral canthal tendon disinsertion results in altered eyelid fissure symmetry, blink dynamics, and lacrimal pump function. The authors recommend the mnemonic-A.B.C.: for Aperture configuration, Blink dynamics, and eyelid Closure-to structure the examination of all symptomatic patients. Manual restoration of the disinserted lateral canthal tendon with the "thumb test" predicts favorable outcomes with surgical fixation.


TRMT10A dysfunction is associated with abnormalities in glucose homeostasis, short stature and microcephaly.
Trm10 is a tRNA m(1)G9 methyltransferase, which in yeast modifies 12 different tRNA species, yet is considered non-essential for viability under standard growth conditions. In humans, there are three Trm10 orthologs, one mitochondrial and two presumed cytoplasmic. A nonsense mutation in one of the cytoplasmic orthologs (TRMT10A) has recently been associated with microcephaly, intellectual disability, short stature and adolescent onset diabetes. The subjects were three patients who suffered from microcephaly, intellectual disability, short stature, delayed puberty, seizures and disturbed glucose metabolism, mainly hyperinsulinaemic hypoglycaemia. A homozygous Gly206Arg (G206R) mutation in the TRMT10A gene was identified using whole exome sequencing. The mutation segregated in the family and was absent from large control cohorts. Determination of the methylation activity of the expressed wild-type (WT) and variant TRMT10A enzymes with transcripts of (32)P -tRNA(Gly) GCC as a substrate revealed a striking defect (<0.1% of WT activity) for the variant enzyme. The binding affinity of the G206R variant enzyme to tRNA, determined by fluorescence anisotropy, was similar to that of the WT enzyme. The completely abolished m(1)G9 methyltransferase activity of the mutant enzyme is likely due to significant defects in its ability to bind the methyl donor S-adenosyl methionine. We propose that TRMT10A deficiency accounts for abnormalities in glucose homeostasis initially manifesting both ketotic and non-ketotic hypoglycaemic events with transition to diabetes in adolescence, perhaps as a consequence of accelerated β cell apoptosis. The seizure disorder and intellectual disability are probably secondary to mutant gene expression in neuronal tissue.


Field application of a rapid spectrophotometric method for determination of persulfate in soil.
Remediation of hydrocarbon contaminated soils can be performed both in situ and ex situ using chemical oxidants such as sodium persulfate. Standard methods for quantifying persulfate require either centrifugation or prolonged settling times. An optimized soil extraction procedure was developed for persulfate involving simple water extraction using a modified disposable syringe. This allows considerable saving of time and removes the need for centrifugation. The extraction time was reduced to only 5 min compared to 15 min for the standard approach. A comparison of the two approaches demonstrated that each provides comparable results. Comparisons were made using high (93 g kg(-1) soil) and low (9.3 g kg(-1) soil) additions of sodium persulfate to a petroleum hydrocarbon-contaminated soil, as well as sand spiked with diesel. Recoveries of 95±1% and 96±10% were observed with the higher application rate in the contaminated soil and spiked sand, respectively. Corresponding recoveries of 86±5% and 117±19% were measured for the lower application rate. Results were obtained in only 25 min and the method is well suited to batch analyses. In addition, it is suitable for application in a small field laboratory or even a mobile, vehicle-based system, as it requires minimal equipment and reagents.


Commissure formation in the embryonic CNS of Drosophila.
Most of the neurons of the ventral nerve cord send out long projecting axons which cross the midline. In the Drosophila central nervous system (CNS) cells of the midline give rise to neuronal and glial lineages with different functions during the establishment of the commissural pattern. Here we present evidence that beside the previously known NETRIN/FRAZZLED (DCC) signalling system an additional attractive system(s) is operating in the developing embryonic nervous system of Drosophila. Attractive cues appear to be provided by the midline neurons. We show that the glial cells present repulsive signals to the previously described ROUNDABOUT receptor in addition to a permissive contact-dependent signal helping commissural growth cones across the midline. A novel repulsive component is encoded by the karussell gene. Furthermore the midline glial cells separate anterior and posterior commissures. By genetic criteria we demonstrate that some of the genes we have identified are acting in the midline glia whereas other genes are required in the midline neurons. The results lead to a detailed model relating different cellular functions to axonal patterning at the midline.


A questionnaire-based survey on the diagnosis and management of inflammatory bowel disease in East Asian countries in 2012.
The prevalence and incidence of inflammatory bowel disease (IBD) are lower in East Asia than in Western countries; however, marked increases have recently been reported. The clinical diagnosis and medical management of IBD in East Asia differ from those in Western countries. A questionnaire-based survey was performed to gather physicians' current opinions on IBD in different East Asian countries. Representative International Gastrointestinal Consensus Symposium (IGICS) committee members provided a questionnaire to physicians in each East Asian country studied. The questionnaire mainly focused on the diagnosis and management of IBD. There were 19 respondents from Japan, 10 from South Korea, 9 from the Philippines, 6 from China and 4 from Indonesia. Colonoscopy (100%) and histopathology (63%) were commonly used for the diagnosis in ulcerative colitis (UC). Conventional small bowel enteroclysis was still the most common diagnostic tool for assessing small bowel lesions in Crohn's disease (CD) in East Asia. The percentage of physicians who investigated the reactivation of Cytomegalovirus in severe or refractory patients with UC ranged from 0% in the Philippines and Indonesia to 100% in Japan and Korea. Most physicians in Korea, the Philippines, China and Indonesia chose thiopurines or anti-TNF therapy as the second-line treatment in severe refractory UC, whereas Japanese physicians preferred to use tacrolimus or leukocyte apheresis. Physicians in the Philippines and Indonesia preferred to use oral 5-aminosalicylic acid for newly diagnosed severe ileocecal CD. In contrast, Korean physicians chose oral steroids and most physicians in China and Japan preferred to use anti-TNF. Nutritional therapy to induce or maintain remission in patients with CD was commonly used in Indonesia, Japan and China. Targeted biopsies by conventional colonoscopy were the most preferred strategy for cancer surveillance in long-standing UC over random biopsies in this region. The present survey found that current diagnostic approaches and clinical management of IBD vary within East Asian countries.


Medication, diagnostic, and cost information as predictors of high-risk patients in need of care management.
To contrast the advantages and limitations of using medication, diagnostic, and cost data to prospectively identify candidates for care management programs. Risk scores from prior-cost information and a set of clinically based predictive models (PMs) derived from diagnostic and medication data sources, as well as from a combination of all 3 data sources, were assigned to a national sample of commercially insured, non-elderly adults (n = 2,259,584). Clinical relevance of risk groups and statistical performance using future costs as the outcome were contrasted across the PMs. Compared with prior cost, diagnostic and medication-based PMs identified high-risk groups with a higher burden of clinically actionable characteristics. Statistical performance was similar and in some cases better for the clinical PMs compared with prior cost. The best classification accuracy was obtained with a comprehensive model that united diagnostic, medication, and prior-cost risk factors. Clinically based PMs are a better choice than prior cost alone for programs that seek to identify high-risk groups of patients who are amenable to care management services.


Wettability influences cell behavior on superhydrophobic surfaces with different topographies.
Surface wettability and topography are recognized as critical factors influencing cell behavior on biomaterials. So far only few works have reported cell responses on surfaces exhibiting extreme wettability in combination with surface topography. The goal of this work is to study whether cell behavior on superhydrophobic surfaces is influenced by surface topography and polymer type. Biomimetic superhydrophobic rough surfaces of polystyrene and poly(L-lactic acid) with different micro/nanotopographies were obtained from smooth surfaces using a simple phase-separation based method. Total protein was quantified and showed a less adsorption of bovine serum albumin onto rough surfaces as compared to smooth surfaces of the same material. The mouse osteoblastic MC3T3-E1 cell line and primary bovine articular chondrocytes were used to study cell attachment and proliferation. Cells attached and proliferate better in the smooth surfaces. The superhydrophobic surfaces allowed cells to adhere but inhibited their proliferation. This study indicates that surface wettability, rather than polymer type or the topography of the superhydrophobic surfaces, is a critical factor in determining cell behavior.


The classification of recurrent overeating: the "binge eating disorder" proposal.
It has been suggested that a new diagnostic category be added to the section on eating disorders in DSM-IV. This new diagnosis has been termed binge eating disorder. In this article we argue that for two main reasons it would be a mistake to include binge eating disorder in DSM-IV: first, too little is known about binge eating and other related forms of recurrent overeating to justify its inclusion in DSM-IV; and second, its inclusion would be a source of diagnostic confusion. We argue that it is premature to crystallize this specific subgroup from amongst those who recurrently overeat and that to do so would impede the acquisition of knowledge rather than enhance it. We advocate a research strategy that involves studying broad samples of those with recurrent overeating rather than narrow ones.


Congenic strains reveal effects of the epilepsy quantitative trait locus, El2, separate from other El loci.
Congenic mouse strains made by transferring epilepsy predisposing alleles El1, El2, and El3 from the EL/Suz strain to the ABP/Le recipient were tested for seizure frequency following gentle rhythmic stimulation. Mice homozygous for El2, but not El1 or El3, experienced seizures much more frequently than ABP controls, while respective El1 homozygotes and El2 heterozygotes had only a modest increase over ABP, and El3 homozygotes showed no increase. Association between marker genotypes and seizure frequency in small intra-strain crosses showed that the phenotypic effects of El2 map to the selected interval, and that segregation of El2 accounts for virtually all genetic effects. However, in separating El2 from other EL susceptibility alleles, the seizure frequency phenotype was weaker and less heritable than in crosses between parental strains. These results confirm El2 as an important QTL and show that it has significant phenotypic effects in the absence of other EL-derived alleles, including El1. In addition, the present localization of El2 on Chr 2 suggests several potential candidate genes for El2, including the beta subunit of phospholipase-C. The approach to dissecting complex traits by making congenic strains for individual QTL is discussed.


Not heading in the right direction: Five hundred psychiatrists' views on resourcing, demand, and workforce across New Zealand mental health services.
To explore the views of psychiatrists (including trainees) regarding the current state and future direction of specialist mental health and addictions services in Aotearoa New Zealand. Psychiatrists and trainee psychiatrists (registrars) in Aotearoa New Zealand were surveyed in August 2021. Of 879 eligible doctors, 540 participated (83% qualified and 17% trainee psychiatrists), a response rate of over 60%. Data were analysed quantitatively and with content analysis. Psychiatrists thought specialist mental health and addictions services had been neglected during recent reforms, with 94% believing current resourcing was insufficient, and only 3% considering future planning was heading in the right direction. The demand and complexity of on-call work had markedly increased in the preceding 2 years. Ninety-eight percent reported that people needing specialist treatment were often (85%) or sometimes (13%) unable to access the right care due to resourcing constraints. The pressures were similar across sub-specialties. A key theme was the distress (sometimes termed 'moral injury') experienced by psychiatrists unable to provide adequate care due to resource limitations, 'knowing what would be a good thing to do and being unable to do it . . . is soul destroying'. Recommendations were made for addressing workforce, service design and wider issues. Most psychiatrists in Aotearoa New Zealand believe the mental health system is not currently fit for purpose and that it is not heading in the right direction. Remedies include urgently addressing identified staffing challenges and boosting designated funding to adequately care for the 5% of New Zealanders with severe mental health and addiction needs.


Fascial anchoring technique in medial thigh lifts.
The medical thigh lift has not gained widespread acceptance since its introduction 20 years ago because of problems such as inferior scar migration, labial separation, and early recurrence of ptosis. Anchoring of the inferior skin flap to the tough, inelastic deep layer of the superficial perineal fascia has reduced such complications. Originally described by Colles in 1811, this fascial layer helps define the perineal-thigh crease. Eighteen patients having medial thigh lifts in combination with liposuction were followed for 6 to 24 months. The technique involves initial liposuction followed by resection of a crescent of redundant skin and fat at the superior medial thigh. The inferior skin flap is suspended from Colles' fascia of the perineum with subdermal PDS sutures. No undermining or deepithelialization of flaps is performed. Complications are few, and patient satisfaction is high.


A pilot study on the effects and feasibility of compassion-focused expressive writing in Day Hospice patients.
Research has found that writing about stress can confer physical and psychological health benefits on participants and that adopting a self-compassionate stance may have additional benefits. This pilot study evaluated a self-compassionate expressive writing intervention in a Day Hospice setting. Thirteen patients with life-limiting illnesses wrote on two occasions about recent stressful experiences. Half also received a self-compassion instruction for their writing. Outcome measures were taken at baseline and one week after the second writing session, and text analysis was used to identify changes in the types of words used, reflecting changes in psychological processes. Patients given the self-compassion instruction increased in their self-soothing and self-esteem in contrast to patients in the stress-only condition. Happiness broadly increased in both groups although reported levels of stress generally increased in patients given the self-compassion instruction but decreased in patients in the stress-only condition. Those given the self-compassion instruction also increased in their use of causal reasoning words across the two writing sessions compared with those in the stress-only condition. Expressive writing appears to be beneficial in patients at a hospice and was viewed as valuable by participants. The inclusion of a self-compassion instruction may have additional benefits and a discussion of the feasibility of implementing expressive writing sessions in a Day Hospice is offered.