Learning Bayesian priors for depth perception.
How the visual system learns the statistical regularities (e.g., symmetry) needed to interpret pictorial cues to depth is one of the outstanding questions in perceptual science. We test the hypothesis that the visual system can adapt its model of the statistics of planar figures for estimating three-dimensional surface orientation. In particular, we test whether subjects, when placed in an environment containing a large proportion of randomly shaped ellipses, learn to give less weight to a prior bias to interpret ellipses as slanted circles when making slant judgments of stereoscopically viewed ellipses. In a first experiment, subjects placed a cylinder onto a stereoscopically viewed, slanted, elliptical surface. In this experiment, subjects received full haptic feedback about the true orientation of the surface at the end of the movement. When test stimuli containing small conflicts between the circle interpretation as figure and the slant suggested by stereoscopic disparities were intermixed with stereoscopically viewed circles, subjects gave the same weight to the circle interpretation over the course of five daily sessions. When the same test stimuli were intermixed with stereoscopic views of randomly shaped ellipses, however, subjects gave progressively lower weights to the circle interpretation of test stimuli over five daily sessions. In a second experiment, subjects showed the same effect when they made perceptual judgments of slant without receiving feedback, showing that feedback is not required for learning. We describe a Bayesian model for combining multiple visual cues to adapt the priors underlying pictorial depth cues that qualitatively accounts for the observed behavior.


Not all patients pursue prostate biopsy after abnormal prostate specific antigen results.
In prostate cancer, digital rectal examination (DRE) and serum prostate specific antigen (PSA) are used to evaluate the risk of prostate cancer. However, in published community-based screening samples, not all patients with abnormal test results pursue biopsy. To test the existence of and quantify diagnostic dropout in clinic-based early detection samples, we conducted a prospective patterns-of-care study designed to identify variables associated with pursuit of diagnostic steps. Of 76 patients with abnormal PSA and/or DRE, only 43 (57%) pursued prostate biopsy. Prostate specific antigen, but not age or chart-based comorbidities, was predictive of further diagnostic and therapeutic steps. Among patients with abnormal test results, age and abnormal PSA and DRE, but not chart-based comorbidities, strongly correlated with physician intention to diagnose prostate cancer. The factors that cause diagnostic dropout are unknown, but based on experience with other cancers, they may relate to psychological variables in tested patients. That pursuit of diagnosis and treatment appears to occur with no association with chart-based comorbidities is worrisome given the power of comorbidities to predict mortality in prostate cancer patients. Finally, from a public health perspective, a reproducible dropout phenomenon implies that the positive predictive value of DRE and PSA testing may be seriously underestimated.


Drug Eruptions: An 8-year Study Including 106 Inpatients at a Dermatology Clinic in Turkey.
Few clinical studies are found in the literature about patients hospitalized with a diagnosis of cutaneous drug eruption. To determine the clinical types of drug eruptions and their causative agents in a hospital-based population. This retrospective study was performed in the Dermatology Department of Haseki General Hospital. Through 1751 patients hospitalized in this department between 2002 and 2009, inpatients diagnosed as drug eruption were evaluated according to WHO causality definitions. 106 patients composed of probable and possible cases of cutaneous drug eruptions were included in this study. Seventy one females and 35 males were evolved. Mean age was 44.03±15.14. Duration between drug intake and onset of reaction varied from 5 minutes to 3 months. The most common clinical type was urticaria and/or angioedema in 48.1% of the patients, followed by maculopapular rash in 13.2%, and drug rash with eosinophilia and systemic symptoms in 8.5%. Drugs most frequently associated with cutaneous drug eruptions were antimicrobial agents in 40.5% of the patients, followed by antipyretic/anti-inflammatory analgesics in 31.1%, and antiepileptics in 11.3%. Urticaria and/or angioedema and maculopapular rash comprised majority of the drug eruptions. Rare reactions such as acute generalized exanthematous pustulosis, sweet syndrome, oral ulceration were also found. Antimicrobial agents and antipyretic/anti-inflammatory analgesics were the most commonly implicated drugs. Infrequently reported adverse reactions to myorelaxant agents, newer cephalosporins and fluoroquinolones were also detected. We suppose that studies on drug eruptions should continue, because the pattern of consumption of drugs is changing in every country at different periods and many new drugs are introduced on the market continuously.


Effect of CYP2E1 gene deletion in mice on expression of microsomal epoxide hydrolase in response to VCD exposure.
Females are born with a finite number of primordial follicles. 4-Vinylcyclohexene diepoxide (VCD) is a metabolite formed by epoxidation of 4-vinylcyclohexene (VCH) via its two monoepoxides 1,2- and 7,8-4-vinylcyclohexene monoepoxide (VCM). VCD specifically destroys small preantral (primordial and small primary) follicles in the rodent ovary. The phase I enzyme, cytochrome P450 isoform 2E1 (CYP2E1) is involved in ovarian metabolism of VCM to VCD. Further, microsomal epoxide hydrolase (mEH) can detoxify VCD to an inactive tetrol (4-(1,2-dihydroxy)ethyl-1,2-dihydroxycyclohexane). This study evaluated the effects of VCD-induced ovotoxicity on mEH in CYP2E1+/+ and -/- mice (129S(1)/SvImJ background strain) using a postnatal day 4 mouse whole ovary culture system. The hypothesis of our study is that there is a relationship between CYP2E1 and mEH gene expression in the mouse ovary. Relative to control, VCD exposure caused follicle loss (p < 0.05) in ovaries from both genotypes; however, after 15 days, this loss was greater (p < 0.05) in CYP2E1+/+ ovaries. In a time course (2-15 days), relative to control, VCD (5 microM) caused an increase (p < 0.05) in mEH mRNA by 0.5-fold (day 10) and 1.84-fold (day 15) in CYP2E1-/- but not +/+ ovaries. 7,12-Dimethylbenz[a]anthracene (DMBA) also destroys ovarian follicles but, unlike VCD, is bioactivated by mEH to an ovotoxic 3,4-diol-1,2-epoxide metabolite. Incubation of ovaries in increasing concentrations of DMBA (0.5-1 microM, 15 days) resulted in greater (p < 0.05) follicle loss in CYP2E1-/-, relative to +/+ ovaries. With greater mEH (CYP2E1-/-), increased follicle loss with DMBA (bioactivation) and decreased follicle loss with VCD (detoxification) support that ovarian expression of CYP2E1 and mEH may be linked.


Novel insights on demographic history of tribal and caste groups from West Maharashtra (India) using genome-wide data.
The South Asian subcontinent is characterized by a complex history of human migrations and population interactions. In this study, we used genome-wide data to provide novel insights on the demographic history and population relationships of six Indo-European populations from the Indian State of West Maharashtra. The samples correspond to two castes (Deshastha Brahmins and Kunbi Marathas) and four tribal groups (Kokana, Warli, Bhil and Pawara). We show that tribal groups have had much smaller effective population sizes than castes, and that genetic drift has had a higher impact in tribal populations. We also show clear affinities between the Bhil and Pawara tribes, and to a lesser extent, between the Warli and Kokana tribes. Our comparisons with available modern and ancient DNA datasets from South Asia indicate that the Brahmin caste has higher Ancient Iranian and Steppe pastoralist contributions than the Kunbi Marathas caste. Additionally, in contrast to the two castes, tribal groups have very high Ancient Ancestral South Indian (AASI) contributions. Indo-European tribal groups tend to have higher Steppe contributions than Dravidian tribal groups, providing further support for the hypothesis that Steppe pastoralists were the source of Indo-European languages in South Asia, as well as Europe.


Use of silicate minerals for pH control during reductive dechlorination of chloroethenes in batch cultures of different microbial consortia.
In chloroethene-contaminated sites undergoing in situ bioremediation, groundwater acidification is a frequent problem in the source zone, and buffering strategies have to be implemented to maintain the pH in the neutral range. An alternative to conventional soluble buffers is silicate mineral particles as a long-term source of alkalinity. In previous studies, the buffering potentials of these minerals have been evaluated based on abiotic dissolution tests and geochemical modeling. In the present study, the buffering potentials of four silicate minerals (andradite, diopside, fayalite, and forsterite) were tested in batch cultures amended with tetrachloroethene (PCE) and inoculated with different organohalide-respiring consortia. Another objective of this study was to determine the influence of pH on the different steps of PCE dechlorination. The consortia showed significant differences in sensitivities toward acidic pH for the different dechlorination steps. Molecular analysis indicated that Dehalococcoides spp. that were present in all consortia were the most pH-sensitive organohalide-respiring guild members compared to Sulfurospirillum spp. and Dehalobacter spp. In batch cultures with silicate mineral particles as pH-buffering agents, all four minerals tested were able to maintain the pH in the appropriate range for reductive dechlorination of chloroethenes. However, complete dechlorination to ethene was observed only with forsterite, diopside, and fayalite. Dissolution of andradite increased the redox potential and did not allow dechlorination. With forsterite, diopside, and fayalite, dechlorination to ethene was observed but at much lower rates for the last two dechlorination steps than with the positive control. This indicated an inhibition effect of silicate minerals and/or their dissolution products on reductive dechlorination of cis-dichloroethene and vinyl chloride. Hence, despite the proven pH-buffering potential of silicate minerals, compatibility with the bacterial community involved in in situ bioremediation has to be carefully evaluated prior to their use for pH control at a specific site.


VEGF-mediated cross-talk within the neonatal murine thymus.
Although the mechanisms of cross-talk that regulate the hematopoietic and epithelial compartments of the thymus are well established, the interactions of these compartments with the thymic endothelium have been largely ignored. Current understanding of the thymic vasculature is based on studies of adult thymus. We show that the neonatal period represents a unique phase of thymic growth and differentiation, marked by endothelium that is organized as primitive, dense networks of capillaries dependent on vascular endothelial growth factor (VEGF). VEGF dependence in neonates is mediated by significantly higher levels of both VEGF production and endothelial VEGF receptor 2 (VEGF-R2) expression than in the adult thymus. VEGF is expressed locally in the neonatal thymus by immature, CD4(-)CD8(-) "double negative" (DN) thymocytes and thymic epithelium. Relative to adult thymus, the neonatal thymus has greater thymocyte proliferation, and a predominance of immature thymocytes and cortical thymic epithelial cells (cTECs). Inhibition of VEGF signaling during the neonatal period results in rapid loss of the dense capillaries in the thymus and a marked reduction in the number of thymocytes. These data demonstrate that, during the early postnatal period, VEGF mediates cross-talk between the thymocyte and endothelial compartments of the thymus.


The opioid antagonist, β-funaltrexamine, inhibits NF-κB signaling and chemokine expression in human astrocytes and in mice.
Opioid-immune crosstalk occurs when opioid drugs alter the activity of the immune system. In this study, the opioid antagonist β-funaltrexamine (β-FNA) decreases the expression and release of an inflammatory chemokine, interferon-γ inducible protein-10 (CXCL10) from normal human astrocytes stimulated by interleukin 1β (IL-1β). β-FNA decreased CXCL10 by an unknown action that did not involve the mu opioid receptor (MOR). As IL-1β acts through its receptor to activate NF-κB/MAPK signaling pathways which leads to CXCL10 expression and release, key steps in the IL-1β signaling pathways were examined following β-FNA treatment. IL-1β-induced activation of p38 mitogen-activated protein kinases (p38 MAPK) was inhibited by β-FNA as shown by decreased p38 MAPK phosphorylation in treated cells. β-FNA also decreased the levels of activated subunits of NF-κB (p50 and p65) in treated astrocytes. The impact of β-FNA was also observed in proteins that act to negatively regulate NF-κB signaling. IL-1β upregulated the expression of A20, a ubiquitin (Ub)-editing enzyme that dampens NF-κB signaling by altering ubiquination patterns on IL-1 receptor second messengers, and the increase in A20 was significantly inhibited by β-FNA treatment. Inhibition of the Ub-activating enzyme E1 by the inhibitor PYR41 also decreased CXCL10 release, like β-FNA, and concurrent treatment with both PYR41 and β-FNA inhibited CXCL10 more than did either agent alone. In mice, lipopolysaccharide-induced CXCL10 expression in the brain was inhibited by treatment with β-FNA. These findings suggest that β-FNA exerts an anti-inflammatory action in vitro and in vivo that is MOR-independent and possibly due to the alkylating ability of β-FNA.


Joyful and serious intentions in the work of hospital clowns: a meta-analysis based on a 7-year research project conducted in three parts.
The present meta-analysis focuses on a 7-year research project entitled "Hospital clowns-in encounters with ailing children" and funded by the Swedish Childhood Cancer Foundation. The aim of the meta-analysis, which is based on the project's three studies, was to attempt to achieve a deeper psychological and more nuanced understanding of the unique encounters taking place between the hospital clowns and ailing children in the study. The methodological procedures were qualitative and included 51 interviews with four informant groups: the clowns, staff, children, and their parents. The meta-analysis revealed the unique aspects of hospital clowns' work with respect to: a) a quality of care that transcends boundaries, that is, a magical safe area where demands and adjustment were temporarily set aside and where the lighter side of life took precedence; b) a non-demanding quality of care, where joy could be experienced without requiring something in return, where the child's terms mattered and where the child perspective was clearly in focus; and c) a defusing quality of care, which is expressed as a positive counterweight that was otherwise lacking in medical care, where the hospital clowns used different solutions that bypassed regular hospital routines by temporarily distracting and making things easier for the children, parents, and staff in various care situations. Finally, the aim of the theoretical framework, in its synthesizing form, was to promote further psychological understanding of the area of humor that exists between fantasy and reality-an intermediate or transitional area that the hospital clowns created together with the children. In this transitional area, the hospital clowns' unique contribution can be interpreted, in psychological terms, as being available as a vicarious therapeutic clown figure in a magical world that parallels reality.


Why open drug discovery needs four simple rules for licensing data and models.
When we look at the rapid growth of scientific databases on the Internet in the past decade, we tend to take the accessibility and provenance of the data for granted. As we see a future of increased database integration, the licensing of the data may be a hurdle that hampers progress and usability. We have formulated four rules for licensing data for open drug discovery, which we propose as a starting point for consideration by databases and for their ultimate adoption. This work could also be extended to the computational models derived from such data. We suggest that scientists in the future will need to consider data licensing before they embark upon re-using such content in databases they construct themselves.


VAV proteins as signal integrators for multi-subunit immune-recognition receptors.
In recent years, substantial progress has been made towards the identification of intracellular signalling molecules that couple multi-subunit immune-recognition receptors (MIRRs) to their various effector functions. Among these, the VAV proteins have been observed to have a crucial role in regulating some of the earliest events in receptor signalling. VAV proteins function, in part, as guanine-nucleotide exchange factors (GEFs) for the RHO/RAC family of GTPases. This review focuses on the role of VAV proteins in the regulation of lymphocyte development and function, and emphasizes the regulatory roles that these proteins have through both GEF-dependent and -independent mechanisms.


Sociality, density-dependence and microclimates determine the persistence of populations suffering from a novel fungal disease, white-nose syndrome.
Disease has caused striking declines in wildlife and threatens numerous species with extinction. Theory suggests that the ecology and density-dependence of transmission dynamics can determine the probability of disease-caused extinction, but few empirical studies have simultaneously examined multiple factors influencing disease impact. We show, in hibernating bats infected with Geomyces destructans, that impacts of disease on solitary species were lower in smaller populations, whereas in socially gregarious species declines were equally severe in populations spanning four orders of magnitude. However, as these gregarious species declined, we observed decreases in social group size that reduced the likelihood of extinction. In addition, disease impacts in these species increased with humidity and temperature such that the coldest and driest roosts provided initial refuge from disease. These results expand our theoretical framework and provide an empirical basis for determining which host species are likely to be driven extinct while management action is still possible.


Face, content and construct validity of a virtual reality simulator for robotic surgery (SEP Robot).
This study aims to establish face, content and construct validation of the SEP Robot (SimSurgery, Oslo, Norway) in order to determine its value as a training tool. The tasks used in the validation of this simulator were arrow manipulation and performing a surgeon's knot. Thirty participants (18 novices, 12 experts) completed the procedures. The simulator was able to differentiate between experts and novices in several respects. The novice group required more time to complete the tasks than the expert group, especially suturing. During the surgeon's knot exercise, experts significantly outperformed novices in maximum tightening stretch, instruments dropped, maximum winding stretch and tool collisions in addition to total task time. A trend was found towards the use of less force by the more experienced participants. The SEP robotic simulator has demonstrated face, content and construct validity as a virtual reality simulator for robotic surgery. With steady increase in adoption of robotic surgery world-wide, this simulator may prove to be a valuable adjunct to clinical mentorship.


Introduction and persistence of tularemia in Bulgaria.
Outbreaks of the zoonotic disease tularemia occurred in north-east Bulgaria in the 1960s. Then came 30 years of epidemiological silence until new outbreaks occurred in west Bulgaria in the 1990s. To investigate how bacterial strains of Francisella tularensis causing tularemia in wildlife and humans in the 1960s and the 1990s were related, we explored their genetic diversity. Ten F. tularensis genomes from the 1960s (n=3) and the 1990s (n=7) were sequenced, assigned to canonical single-nucleotide polymorphism (canSNP) clades, and compared to reference genomes. We developed four new canSNP polymerase chain reaction (PCR) assays based on the genome sequence information. The genetic analysis showed that the outbreaks in the 1960s as well as in the 1990s involved multiple clones and new genetic diversity. The smallest genetic difference found between any of the Bulgarian strains was five SNPs between the strains L2 and 81 isolated 43 years apart, indicating that F. tularensis may persist locally over long time periods without causing outbreaks. The existence of genetically highly similar strain-pairs isolated the same year in the same area from different hosts supports a hypothesis of local expansion of clones during outbreaks. Close relationship (two SNPs) was found between one strain isolated 1961 in northeast Bulgaria and one strain isolated 5 years before in USSR. Historical data coinciding with the actual time point describe the introduction of water rats from USSR into the Bulgarian outbreak area, which may explain the close genetic relationship and the origin of the outbreak. Genome analysis of strains from two outbreaks in the 1960s and the 1990s provided valuable information on the genetic diversity and persistence of F. tularensis in Bulgaria.


The Use of Finite Element Analyses to Design and Fabricate Three-Dimensional Scaffolds for Skeletal Tissue Engineering.
Computational modeling has been increasingly applied to the field of tissue engineering and regenerative medicine. Where in early days computational models were used to better understand the biomechanical requirements of targeted tissues to be regenerated, recently, more and more models are formulated to combine such biomechanical requirements with cell fate predictions to aid in the design of functional three-dimensional scaffolds. In this review, we highlight how computational modeling has been used to understand the mechanisms behind tissue formation and can be used for more rational and biomimetic scaffold-based tissue regeneration strategies. With a particular focus on musculoskeletal tissues, we discuss recent models attempting to predict cell activity in relation to specific mechanical and physical stimuli that can be applied to them through porous three-dimensional scaffolds. In doing so, we review the most common scaffold fabrication methods, with a critical view on those technologies that offer better properties to be more easily combined with computational modeling. Finally, we discuss how modeling, and in particular finite element analysis, can be used to optimize the design of scaffolds for skeletal tissue regeneration.


Can the world afford to ignore biotechnology solutions that address food insecurity?
Genetically engineered (GE) crops can be used as part of a combined strategy to address food insecurity, which is defined as a lack of sustainable access to safe and nutritious food. In this article, we discuss the causes and consequences of food insecurity in the developing world, and the indirect economic impact on industrialized countries. We dissect the healthcare costs and lost productivity caused by food insecurity, and evaluate the relative merits of different intervention programs including supplementation, fortification and the deployment of GE crops with higher yields and enhanced nutritional properties. We provide clear evidence for the numerous potential benefits of GE crops, particularly for small-scale and subsistence farmers. GE crops with enhanced yields and nutritional properties constitute a vital component of any comprehensive strategy to tackle poverty, hunger and malnutrition in developing countries and thus reduce the global negative economic effects of food insecurity.


A pause site for RNA polymerase II is associated with termination of transcription.
Termination of transcription by RNA polymerase II has been postulated to involve a pausing process. We have identified such a pause signal, 350 bp into the 3' flanking region of the human alpha 2 globin gene at a position where termination is thought to occur. We show that this pause signal enhances the utilization of an upstream poly(A) site which is otherwise out-competed by a stronger downstream poly(A) site. We also demonstrate that the pause site rescues a poly(A) site that is inactive due to its location within an intron. Using nuclear run-on analysis we show that elongating RNA polymerase II molecules accumulate over this pause signal. Furthermore we show that when the pause site is positioned immediately downstream of a strong poly(A) signal, significant levels of transcription termination take place.


Ruptured Hemorrhagic Cyst of Undescended Ovary Mimicking Mucocele: A Rare Pediatric Case.
Undescended ovary is a rare entity and usually presentedas a case report. It is associated with urinary and uterine anomalies. Symptomatic patients are diagnosed during surgery. Most of the patients are asymptomatic and treatment is unnecessary. They are incidentally diagnosed during infertility evaluation and treatment such as ovarian hyperstimulation studies. A 15-year-old female patient presented with the diagnosis of renal cystic massas identifiedduring ultrasonography in another hospital. Abdominal computedtomography image was requested. A cystic lesion of about 48×34 mm with well-defined borders associated with the appendix and probably with mucocele of the appendix was reported in the lower right abdominal quadrant close to the cecum. During exploration, the right ovary was seen to be attached to the cecum and was higher in position as well as a right ovary originated cystic structure of 5×5 cm. Using needle aspiration, intraovarian hemorrhage was confirmed and partial cystectomy was performed. The present study reports on an undescended ovary that hadacute abdomen symptoms imitating mucocele. In girls referring to the hospital with abdominal pain, although quite rare, undescended ovaries are to be also considered. As the incidence of renal and uterine anomalies is higher in suchpatients, in symptomatic cases relevant organs are to be investigated carefully during surgical intervention.


Factors influencing adherence to mammography screening guidelines in Appalachian women participating in a mobile mammography program.
The objectives of this study were to evaluate the characteristics (demographic, access to care, health-related behavioral, self and family medical history, psychosocial) of women age 40 years and above who participated in a mobile mammography screening program conducted throughout West Virginia (WV) to determine the factors influencing their self-reported adherence to mammography screening guidelines. Data were analyzed using the Andersen Behavioral Model of Healthcare Utilization framework to determine the factors associated with adherence to mammography screening guidelines in these women. Of the 686 women included in the analysis, 46.2% reported having had a mammogram in the past 2 years. Bivariate analyses showed predisposing factors such as older age and unemployed status, visit to a obstetrician/gynecologist (OB/GYN) in the past year (an enabling factor) and need-related factors such as having a family history of breast cancer (BC), having had breast problems in the past, having had breast biopsy in the past, having had a Pap test in past 2 years, and having had all the screenings for cholesterol, blood glucose, bone mineral density and high blood pressure in past 2 years to be significant predictors of self-reported adherence to mammography guidelines. In the final model, being above 50 years (OR=2.132), being morbidly obese (OR=2.358), having BC-related events and low knowledge about mammography were significant predictors of self-reported adherence. Breast cancer related events seem to be associated with mammography screening adherence in this rural Appalachian population. Increasing adherence to mammography screening may require targeted, community-based educational interventions that precede and complement visits by the mobile mammography unit.


Juglanconis gen. nov. on Juglandaceae, and the new family Juglanconidaceae (Diaporthales).
Molecular phylogenetic analyses of ITS-LSU rDNA sequence data demonstrate that Melanconis species occurring on Juglandaceae are phylogenetically distinct from Melanconis s.str., and therefore the new genus Juglanconis is described. Morphologically, the genus Juglanconis differs from Melanconis by light to dark brown conidia with irregular verrucae on the inner surface of the conidial wall, while in Melanconis s.str. they are smooth. Juglanconis forms a separate clade not affiliated with a described family of Diaporthales, and the family Juglanconidaceae is introduced to accommodate it. Data of macro- and microscopic morphology and phylogenetic multilocus analyses of partial nuSSU-ITS-LSU rDNA, cal, his, ms204, rpb1, rpb2, tef1 and tub2 sequences revealed four distinct species of Juglanconis. Comparison of the markers revealed that tef1 introns are the best performing markers for species delimitation, followed by cal, ms204 and tub2. The ITS, which is the primary barcoding locus for fungi, is amongst the poorest performing markers analysed, due to the comparatively low number of informative characters. Melanconium juglandinum (= Melanconis carthusiana), M. oblongum (= Melanconis juglandis) and M. pterocaryae are formally combined into Juglanconis, and J. appendiculata is described as a new species. Melanconium juglandinum and Melanconis carthusiana are neotypified and M. oblongum and Diaporthe juglandis are lectotypified. A short description and illustrations of the holotype of Melanconium ershadii from Pterocarya fraxinifolia are given, but based on morphology it is not considered to belong to Juglanconis. A key to all treated species of Juglanconis is provided.


A similarity measure for two-dimensional fluorescent spectra.
A similarity measure was developed that can differentiate between two-dimensional fluorescent spectra based on their similarities and differences. The two-dimensional fluorescent spectra are digitalized into matrices. The difference between the two spectra is defined by a difference matrix, whose elements contain the difference of one two-dimensional fluorescent spectrum minus the other. The similarity measure is transformed into hypothesis tests of the similarity and difference between the two spectra. The scalar mean of the difference matrix is used as the statistical variable for the hypothesis test. The Bayesian prior odds ratio was estimated from multiple spectra of the same reference sample. A threshold for the hypothesis test that the spectra are different is proposed. The posterior odds ratio was used to quantify the similarity measure of the two spectra. Two-dimensional fluorescent spectra of Changyu red wine samples were used to demonstrate this method. The results show that this new method can detect differences between the spectra.


Clinical, Electrodiagnostic, and Genetic Features of Tangier Disease in an Adolescent Girl with Presentation of Peripheral Neuropathy.
Tangier disease (TD) is a rare, autosomal recessive inherited disorder caused by a mutation in the adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene, which results in a decrease in plasma high-density lipoprotein (HDL) levels. Peripheral neuropathy can be seen in approximately 50% of patients with TD, which usually occurs after the age of 15 years, and is characterized by relapsing-remitting mono- or polyneuropathy or syringomyelia-like neuropathy. Herein, we report a 16-year-old female patient who was initially diagnosed with peripheral neuropathy at the age of 13 years. Whole exome sequencing was performed, and a nonsense mutation (p.Arg1817X) in ABCA1 was identified. The patient was investigated for systemic findings of TD after the genetic diagnosis was made, and low (< 5 mg/dL) levels of HDL cholesterol were detected by lipid electrophoresis. Other family members were reexamined after the diagnosis of the proband, and asymptomatic sister of the proband was diagnosed with TD. We would like to emphasize that TD should be considered in the differential diagnosis of pediatric patients presenting with peripheral neuropathy; furthermore detection of HDL levels by lipid electrophoresis is a simple but indicative diagnostic test.


Inferring biological evolution from fracture patterns in teeth.
It is hypothesised that specific tooth forms are adapted to resist fracture, in order to accommodate the high bite forces needed to secure, break down and consume food. Three distinct modes of tooth fracture are identified: longitudinal fracture, where cracks run vertically between the occlusal contact and the crown margin (or vice versa) within the enamel side wall; chipping fracture, where cracks run from near the edge of the occlusal surface to form a spall in the enamel at the side wall; and transverse fracture, where a crack runs horizontally through the entire section of the tooth to break off a fragment and expose the inner pulp. Explicit equations are presented expressing critical bite force for each fracture mode in terms of characteristic tooth dimensions. Distinctive transitions between modes occur depending on tooth form and size, and loading location and direction. Attention is focussed on the relatively flat, low-crowned molars of omnivorous mammals, including humans and other hominins and the elongate canines of living carnivores. At the same time, allusion to other tooth forms - the canines of the extinct sabre-tooth (Smilodon fatalis), the conical dentition of reptiles, and the columnar teeth of herbivores - is made to highlight the generality of the methodology. How these considerations impact on dietary behaviour in fossil and living taxa is discussed.


Computer-aided speckle pattern interferometry.
An on-line computer system for measuring the deformation of a diffuse object with a speckle interferometer is presented. Methods for evaluating a speckle interferogram using digital image processing techniques are also discussed. The system consists of an interferometric optical setup and a computer-TV image processing facility. A speckle interferogram is generated arithmetically between two digitized speckle patterns before and after deformation of the object. The information about the deformation is extracted by two procedures in analyzing the interferogram: (a) automatic analysis using digital image processing techniques such as gray scale modification, linear spatial filtering, thresholding, and skeletoning; (b) man-machine interactive method for simple high-speed processing of the interferogram using a light pen. The determined fringe order numbers are interpolated and differentiated spatially to give strain, slope, and bending moment of the deformed object. Some examples of processed patterns are presented.


Master mode-locking theory for few-femtosecond pulses.
We propose a model that is valid for ultrafast pulse propagation in a mode-locked laser cavity in the few-femtosecond pulse regime, thus deriving the equivalent of the master mode-locking equation for ultrashort pulses that has dominated mode-locking theory for two decades. The short-pulse equation with dissipative gain and loss terms allows for the generation of stable ultrashort optical pulses from initial white noise, thus providing the first theoretical framework for quantifying the pulse dynamics and stability as pulses widths approach the attosecond regime.


Immunohistochemical quantification of substance P in spinal dorsal horns of patients with multiple system atrophy.
Using a computer-assisted image analyser, an immunohistochemical quantification method of substance P-like immunoreactivity (SPLI) in laminae I + II of spinal dorsal horn was established and applied to 13 patients with multiple system atrophy (MSA) with no disturbance of pain sensation, including olivo-ponto-cerebellar atrophy and striatonigral degeneration, and 13 neurologically normal controls. To investigate whether alteration of SPLI is related to an autonomic disorder, myelinated fibre counts of the fourth thoracic ventral roots were performed. Eleven of 13 MSA patients showed a significant decrease in small and large myelinated fibres, and were diagnosed with definite Shy-Drager syndrome (SDS), with the exception of two who had no apparent history of autonomic dysfunction. SPLIs in laminae I + II in 10 of these 11 patients, when adjusted for age, were significantly decreased at both levels of the fourth thoracic and third lumbar spinal segments. The results suggest the disorder of SP-containing synapses of primary afferent neurons and/or those of interneurons in SDS.


Phosphorylation of the RNA polymerase II carboxy-terminal domain by the Bur1 cyclin-dependent kinase.
BUR1, which was previously identified by a selection for mutations that have general effects on transcription in Saccharomyces cerevisiae, encodes a cyclin-dependent kinase that is essential for viability, but none of its substrates have been identified to date. Using an unbiased biochemical approach, we have identified the carboxy-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II, as a Bur1 substrate. Phosphorylation of Rpb1 by Bur1 is likely to be physiologically relevant, since bur1 mutations interact genetically with rpb1 CTD truncations and with mutations in other genes involved in CTD function. Several genetic interactions are presented, implying a role for Bur1 during transcriptional elongation. These results identify Bur1 as a fourth S. cerevisiae CTD kinase and provide striking functional similarities between Bur1 and metazoan P-TEFb.


Highly efficient direct oxygen electro-reduction by partially unfolded laccases immobilized on waste-derived magnetically separable nanoparticles.
A biocatalytic system based on laccase functionalized waste-derived iron oxide nanoparticles (LAC-DA-Fe2O3) was designed by a mechanochemical approach and employed in the electrocatalytic reduction of oxygen. Full characterization of the obtained bioconjugates revealed that the protein adopted a partially unfolded state. The mentioned configuration, together with the geometry coordination changes along the T1 center can be further related to a high bioelectrocatalytic response. A current density up to 2.9 mA cm-2 has been achieved, which is among the highest values reported in literature for laccase functionalized nanomaterials.


Men with cancer. Changes in attempts to master the self-image as a man and as a parent.
Little is known about men's experience of how cancer affects their role as a father. The aim of this study was to gain an understanding of changes in these men's everyday family lives. The study had an interpretative descriptive design, utilizing the concept of transition as a fore structure. Eight men with different types of blood cancer and with children living at home were recruited for the study. Interviews, guided by the main components of the concept of transition, provided qualitative data for analysis. Through the interpretative process, the central theme--change in self-image as a man and as a parent--was generated. This theme consists of the subthemes gaining control, balancing emotions, subjective well-being, being open or not toward the family, and challenges in family life and to family well-being. The time after diagnosis influenced the process of transition. Self-image changes are more obvious shortly after diagnosis. Further study is needed to identify how nurses and other clinicians can assess the family's needs and support the parental role, especially in consideration of the findings of this study.


Influence of CH···N Interaction in the Self-Assembly of an Oligo(isoquinolyne-ethynylyne) Molecule with Distinct Conformational States.
Molecular conformational flexibility can play an important role in supramolecular self-assembly on surfaces, affecting not least chiral molecular assemblies. To explicitly and systematically investigate the role of molecular conformational flexibility in surface self-assembly, we synthesized a three-bit conformational switch where each of three switching units on the molecules can assume one of two distinct binary positions on the surface. The molecules are designed to promote C-H···N type hydrogen bonds between the switching units. While supramolecular self-assembly based on strong hydrogen-bonding interactions has been widely explored, less is known about the role of such weaker directional interactions for surface self-assembly. The synthesized molecules consist of three nitrogen-containing isoquinoline (IQ) bits connected by ethynylene spokes and terminated by tert-butyl (tBu) groups. Using high-resolution scanning tunnelling microscopy, we investigate the self-assembly of the IQ-tBu molecules on a Au(111) surface under ultrahigh-vacuum conditions. The molecules form extended domains of brick-wall structure where the molecular backbones are packed regularly but without selection of specific molecular conformations. However, statistical analysis of the extended network demonstrates alignment/correlation for the orientations of the switching units indicating specific interactions. The primary interaction motifs in the structure are quantified from DFT calculations, showing that the brick-wall structure is indeed stabilized by two types of weak C-H···N bonds, involving either aromatic hydrogens on the IQ groups or nonaromatic hydrogens on the tBu groups. Analysis of the C-H···N interactions in the brick-wall structure explains the observed distribution and alignment of molecular conformations as well as the overall organization of the molecular surface structures.


Contributions of Zea mays subspecies mexicana haplotypes to modern maize.
Maize was domesticated from lowland teosinte (Zea mays ssp. parviglumis), but the contribution of highland teosinte (Zea mays ssp. mexicana, hereafter mexicana) to modern maize is not clear. Here, two genomes for Mo17 (a modern maize inbred) and mexicana are assembled using a meta-assembly strategy after sequencing of 10 lines derived from a maize-teosinte cross. Comparative analyses reveal a high level of diversity between Mo17, B73, and mexicana, including three Mb-size structural rearrangements. The maize spontaneous mutation rate is estimated to be 2.17 × 10-8 ~3.87 × 10-8 per site per generation with a nonrandom distribution across the genome. A higher deleterious mutation rate is observed in the pericentromeric regions, and might be caused by differences in recombination frequency. Over 10% of the maize genome shows evidence of introgression from the mexicana genome, suggesting that mexicana contributed to maize adaptation and improvement. Our data offer a rich resource for constructing the pan-genome of Zea mays and genetic improvement of modern maize varieties.


Cardiac performance of isolated perfused hearts from alloxan diabetic rats.
Acute alloxan diabetes (3 days) in the rat resulted in a decreased ability of the isolated perfused working heart to respond to increased atrial filling pressure with normal systolic (aortic) pressure development, using a physiologic concentration of glucose (5 mM) as substrate. The diabetic heart also exhibited impaired cardiac output, which could be attributed entirely to decreased aortic output without any apparent effect on coronary flow. This decrease in ventricular performance was accompanied by a 40% reduction in glucose uptake and a 20% reduction in tissue ATP concentrations even though perfusate glucose levels remained at or near physiologic levels. Perfusion of hearts with 5 mM glucose plus 10(-8) M insulin, with 10 or 30 mM glucose, or 1 mM octanoate reversed the diabetes-related decrease in systolic pressure development, cardiac output, and tissue ATP content. These data demonstrate that the defect in cardiac performance with increased work loads associated with acute insulin deficiency is due to the relative inability of the heart to utilize physiologic concentrations of glucose as substrate for energy production.


Highly coherent injection-seeded 13.2 nm tabletop soft x-ray laser.
We report a dramatic improvement of the spatial coherence and beam divergence (0.66 mrad) of a 13.2 nm wavelength Ni-like Cd tabletop laser by injection seeding the soft x-ray laser amplifier with high-harmonics pulses generated in a Ne gas jet. This phase coherent laser is an attractive light source for at-wavelength interferometry of extreme ultraviolet lithography optics and other applications.


7 billion and counting.
The world is currently in the midst of the greatest demographic upheaval in human history. Dramatic reductions in mortality, followed (but with a lag) by equally marked reductions in fertility, resulted in a doubling of world population between 1960 and 2000. A further increase of 2 to 4.5 billion is projected for the current half-century, with the increase concentrated in the world's least developed countries. Despite alarmist predictions, historical increases in population have not been economically catastrophic. Moreover, changes in population age structure have opened the door to increased prosperity. Demographic changes have had and will continue to have profound repercussions for human well-being and progress, with some possibilities for mediating those repercussions through policy intervention.


Functional MRI of the mouse olfactory system.
Although olfactory dysfunction is an early warning sign of Alzheimer's and Parkinson's diseases, and is commonly present in a range of other neurodegenerative disorders, the mechanisms for its pathogenesis are not yet clear. Since fMRI allows the mapping of spatial and temporal patterns of activity in multiple brain regions simultaneously, it serves as a powerful tool to study olfactory dysfunction in animal models of neurodegenerative diseases. Nonetheless, there have been no reports to date of mapping odor-induced activation patterns beyond the olfactory bulb to the extended networks of olfactory and limbic archicortex, likely due to the small size of the mouse brain. Therefore, using an 11.7 T magnet and a blood volume-weighted fMRI technique, we mapped the functional neuroanatomy of the mouse olfactory system. Consistent with reports on imaging of the much larger human brain, we mapped activity in regions of the olfactory bulb, as well as olfactory and limbic archicortex. By using two distinct odorants, we further demonstrated odorant-specific activation patterns. Our work thus provides a methodological framework for fMRI studies of olfactory dysfunction in mouse models of neurodegeneration.


Expression cloning of an equine T-lymphocyte glycoprotein CD2 cDNA. Structure-based analysis of conserved sequence elements.
An equine CD2 cDNA has been isolated by monoclonal antibody screening of a T-lymphocyte cDNA library. The cDNA contained an open reading frame of 1041 bp encoding a translated product of 347 amino acids. Northern blotting analysis revealed a single mRNA species expressed in spleen, thymus and activated peripheral lymphocytes. The predicted amino acid sequence has 50-65% identity with the human, rat and mouse CD2 sequences with greatest similarity shared with the human homologue. Evolutionarily conserved structural and functional domains in CD2 were identified by comparing the sequences of the equine, human, mouse and rat CD2 homologues in the context of the recently derived crystal structure of rat soluble CD2 [Jones, E. Y., Davis, S. J., Williams, A. F., Harlos, K. & Stuart, D. I. (1992) Nature 360, 232-239]. The key conserved features of the extracellular region included core residues necessary to preserve the structural integrity of the molecule, residues in the linker region likely to maintain the unique domain organization of CD2, an array of highly charged residues in the putative ligand-binding face of the molecule and glycosylation-signal distributions that render the putative ligand-binding GFCC'C" face of domain 1 relatively unhindered by glycosylation.


Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors.
The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.


Dose-response relationships between physical activity, walking and health-related quality of life in mid-age and older women.
Although physical activity is associated with health-related quality of life (HRQL), the nature of the dose-response relationship remains unclear. To examine the concurrent and prospective dose-response relationships between total physical activity (TPA) and (only) walking with HRQL in two age cohorts of women. Participants were 10 698 women born in 1946-1951 and 7646 born in 1921-1926, who completed three mailed surveys for the Australian Longitudinal Study on Women's Health. They reported weekly TPA minutes (sum of walking, moderate and vigorous minutes). HRQL was measured with the Medical Outcomes Study Short-Form 36 Health Status Survey (SF-36). Linear mixed models, adjusted for socio-demographic and health-related variables, were used to examine associations between TPA level (none, very low, low, intermediate, sufficient, high and very high) and SF-36 scores. For women who reported walking as their only physical activity, associations between walking and SF-36 scores were also examined. Curvilinear trends were observed between TPA and walking with SF-36 scores. Concurrently, HRQL scores increased significantly with increasing TPA and walking, in both cohorts, with increases less marked above sufficient activity levels. Prospectively, associations were attenuated although significant and meaningful improvements in physical functioning and vitality were observed across most TPA and walking categories above the low category. For women in their 50s-80s without clinical depression, greater amounts of TPA are associated with better current and future HRQL, particularly physical functioning and vitality. Even if walking is their only activity, women, particularly those in their 70s-80s, have better HRQL.


The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo.
Both epigallocatechin gallate (EGCG) and curcumin have shown efficacy in various in vivo and in vitro models of cancer. This study was designed to determine the efficacy of these naturally derived polyphenolic compounds in vitro and in vivo, when given in combination. Studies in MDA-MB-231 cells demonstrated that EGCG + curcumin was synergistically cytotoxic and that this correlated with G(2)/M-phase cell cycle arrest. After 12 hr, EGCG (25 microM) + curcumin (3 microM) increased the proportion of cells in G(2)/M-phase to 263 +/- 16% of control and this correlated with a 50 +/- 4% decrease in cell number compared to control. To determine if this in vitro result would translate in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with curcumin (200 mg/kg/day, po), EGCG (25 mg/kg/day, ip), EGCG + curcumin, or vehicle control (5 ml/kg/day, po) for 10 weeks. Tumor volume in the EGCG + curcumin treated mice decreased 49% compared to vehicle control mice (p < 0.05), which correlated with a 78 +/- 6% decrease in levels of VEGFR-1 protein expression in the tumors. Curcumin treatment significantly decreased tumor protein levels of EGFR and Akt, however the expression of these proteins was not further decreased following combination treatment. Therefore, these results demonstrate that the combination of EGCG and curcumin is efficacious in both in vitro and in vivo models of ER alpha-breast cancer and that regulation of VEGFR-1 may play a key role in this effect.


Systematic review and meta-analysis of immunosuppressant therapy clinical trials in membranous lupus nephritis.
We performed a systematic review and meta-analysis to compare response rates (complete remission plus partial remission) for nonsteroid immunosuppressant therapy to steroid-only immunosuppressant therapy in patients with membranous lupus nephritis. A literature review was conducted from June 25, 2010 by querying PubMed, MEDLINE, and EMBASE databases. Inclusion criteria were trials containing remission data on patients with confirmed pure class V (Va and Vb) membranous lupus nephritis. The primary analysis evaluates response rates for regimens that contain at least one nonsteroid immunosuppressant therapy and steroid-only immunosuppressant therapy. A proportion meta-analysis using a DerSimonian-Laird random-effects model was performed. Data are reported as pooled proportions in percentages with 95% confidence intervals. Significant heterogeneity and/or bias were compensated for by trial exclusion. Twenty-four studies met inclusion criteria for meta-analysis, which yielded 34 groups of patients' data. Upon meta-analysis, the response rate for nonsteroid immunosuppressant therapy is higher than for steroids alone (81% [74%-87%] vs 60% [39%-79%]), even when compensating for significant heterogeneity and bias (76% [71%-81%] versus 60% [39%-79%]). Nonsteroid immunosuppressant therapies in combination with steroids seem to be more effective than steroids alone for inducing partial or complete remission in patients with membranous lupus nephritis who have nephrotic proteinuria at baseline. This trial was not able to analyze adverse events, flares, relapses, or patient survival because of underreporting.


InterVA-4 as a public health tool for measuring HIV/AIDS mortality: a validation study from five African countries.
Reliable population-based data on HIV infection and AIDS mortality in sub-Saharan Africa are scanty, even though that is the region where most of the world's AIDS deaths occur. There is therefore a great need for reliable and valid public health tools for assessing AIDS mortality. The aim of this article is to validate the InterVA-4 verbal autopsy (VA) interpretative model within African populations where HIV sero-status is recorded on a prospective basis, and examine the distribution of cause-specific mortality among HIV-positive and HIV-negative people. Data from six sites of the Alpha Network, including HIV sero-status and VA interviews, were pooled. VA data according to the 2012 WHO format were extracted, and processed using the InterVA-4 model into likely causes of death. The model was blinded to the sero-status data. Cases with known pre-mortem HIV infection status were used to determine the specificity with which InterVA-4 could attribute HIV/AIDS as a cause of death. Cause-specific mortality fractions by HIV infection status were calculated, and a person-time model was built to analyse adjusted cause-specific mortality rate ratios. The InterVA-4 model identified HIV/AIDS-related deaths with a specificity of 90.1% (95% CI 88.7-91.4%). Overall sensitivity could not be calculated, because HIV-positive people die from a range of causes. In a person-time model including 1,739 deaths in 1,161,688 HIV-negative person-years observed and 2,890 deaths in 75,110 HIV-positive person-years observed, the mortality ratio HIV-positive:negative was 29.0 (95% CI 27.1-31.0), after adjustment for age, sex, and study site. Cause-specific HIV-positive:negative mortality ratios for acute respiratory infections, HIV/AIDS-related deaths, meningitis, tuberculosis, and malnutrition were higher than the all-cause ratio; all causes had HIV-positive:negative mortality ratios significantly higher than unity. These results were generally consistent with relatively small post-mortem and hospital-based diagnosis studies in the literature. The high specificity in cause of death attribution achieved in relation to HIV status, and large differences between specific causes by HIV status, show that InterVA-4 is an effective and valid tool for assessing HIV-related mortality.


Pediatric tracheostomy.
To provide an up-to-date review of pediatric tracheostomy, primarily focusing on indications, surgical technique, complications and hospital and home care. MEDLINE and PubMed databases were searched using the following keywords: tracheostomy, tracheotomy, children, newborn. Indications for tracheostomy in children are changing. Today the most common indication is prolonged ventilation. The age at the time of the procedure has also changed, with a peak incidence of tracheostomy in patients less than 1 year old. Except under emergency conditions, pediatric tracheostomy should be performed in the operating room with the child intubated. A horizontal skin incision with vertical tracheal incision and no tracheal resection is recommended. Although post-tracheostomy complications are not uncommon, they usually do not need special treatment or surgical procedures. Tracheostomy mortality can occur in up to 40% of pediatric cases, however the tracheostomy-related mortality rate is only 0 to 6%. The decision to perform a tracheostomy remains complex, and depends on several factors. The procedure is safe and with a low number of complications if carried out at a tertiary hospital by a trained and experienced team.


Urologists' Perceptions and Practice Patterns in Peyronie's Disease: A Korean Nationwide Survey Including Patient Satisfaction.
A nationwide survey was conducted of Korean urologists to illustrate physicians' perceptions and real practical patterns regarding Peyronie disease (PD). A specially designed questionnaire exploring practice characteristics and attitudes regarding PD, as well as patient satisfaction with each treatment modality, was e-mailed to 2,421 randomly selected urologists. Responses were received from 385 practicing urologists (15.9%) with a median time after certification as an urologist of 12 years. Regarding the natural course, 87% of respondents believed that PD is a progressive disease, and 82% replied that spontaneous healing in PD occurred in fewer than 20% of patients. Regarding diagnosis of PD, the methods used were, in order, history taking with physical examination (98%), International Index of Erectile Function questionnaires (40%), intracavernous injection and stimulation (35%), and duplex sonography (28%). Vitamin E was most preferred as an initial medical management (80.2%), followed by phosphodiesterase-5 inhibitors (27.4%) and Potaba (aminobenzoate potassium, 20.1%). For urologists who administered intralesional injection, the injected agent was, in order, corticosteroid (72.2%), verapamil (45.1%), and interferon (3.2%). The most frequently performed surgical procedure was plication (84.1%), followed by excision and graft (42.9%) and penile prosthesis implantation (14.2%). Among the most popular treatments in each modality, the urologists' perceptions regarding the suitability of treatment and patient satisfaction were significantly different, favoring plication surgery. The practice pattern of urologists depicted in this survey is in line with currently available Western guidelines, which indicates the need for development of further local guidelines based on solid clinical data.


Addressing uncertainty in atomistic machine learning.
Machine-learning regression has been demonstrated to precisely emulate the potential energy and forces that are output from more expensive electronic-structure calculations. However, to predict new regions of the potential energy surface, an assessment must be made of the credibility of the predictions. In this perspective, we address the types of errors that might arise in atomistic machine learning, the unique aspects of atomistic simulations that make machine-learning challenging, and highlight how uncertainty analysis can be used to assess the validity of machine-learning predictions. We suggest this will allow researchers to more fully use machine learning for the routine acceleration of large, high-accuracy, or extended-time simulations. In our demonstrations, we use a bootstrap ensemble of neural network-based calculators, and show that the width of the ensemble can provide an estimate of the uncertainty when the width is comparable to that in the training data. Intriguingly, we also show that the uncertainty can be localized to specific atoms in the simulation, which may offer hints for the generation of training data to strategically improve the machine-learned representation.


Field grand challenge with emerging superbugs and the novel coronavirus (SARS-CoV-2) on plastics and in water.
This opinion paper reports field grand challenges associated with plastic and water contaminated with the novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) and superbugs, given the emergency of public health and environmental protection from the presence of lethal viruses and bacteria. Two primary focuses of detection and treatment methods for superbugs and the novel coronavirus (SARS-CoV-2) are investigated, and the future outlook is provided based on grand challenges identified in the water field. Applying conventional treatment technologies to treat superbugs or the novel coronavirus (SARS-CoV-2) has brought negative results, including ineffective treatment, formation of toxic byproducts, and limitation of long-term performance. Existing detection methods are not feasible to apply in terms of sensitivity, difficulty of applications in field samples, speed, and accuracy at the time of sample collection. Few studies are found on superbugs or adsorption of the novel coronavirus (SARS-CoV-2) on plastic, as well as effects of superbugs or the novel coronavirus (SARS-CoV-2) on treatment of plastic waste and wastewater. With the need for and directions of further research and challenges discussed in this paper, we believe that this opinion paper offers information useful to a wide audience, including scientists, policy makers, consultants, public health workers, and field engineers in the water sector.


Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans.
Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.


Pattern identification and characterization reveal permutations of organs as a key genetically controlled property of post-meristematic phyllotaxis.
In vascular plants, the arrangement of organs around the stem generates geometric patterns called phyllotaxis. In the model plant, Arabidopsis thaliana, as in the majority of species, single organs are initiated successively at a divergence angle from the previous organ close to the canonical angle of 137.5°, producing a Fibonacci spiral. Given that little is known about the robustness of these geometric arrangements, we undertook to characterize phyllotaxis by measuring divergence angles between organs along the stems of wild-type and specific mutant plants with obvious defects in phyllotaxis. Sequences of measured divergence angles exhibit segments of non-canonical angles in both genotypes, albeit to a far greater extent in the mutant. We thus designed a pipeline of methods for analyzing these perturbations. The latent structure models used in this pipeline combine a non-observable model representing perturbation patterns (either a variable-order Markov chain or a combinatorial model) with von Mises distributions representing divergence angle uncertainty. We show that the segments of non-canonical angles in both wild-type and mutant plants can be explained by permutations in the order of insertion along the stem of two or three consecutive organs. The number of successive organs between two permutations reveals specific patterns that depend on the nature of the preceding permutation (2- or 3-permutation). We also highlight significant individual deviations from 137.5° in the level of baseline segments and a marked relationship between permutation of organs and defects in the elongation of the internodes between these organs. These results demonstrate that permutations are an intrinsic property of spiral phyllotaxis and that their occurrence is genetically regulated.


Photographic Measurements Partially Correlate to Nasal Function and Appearance among Adult Cleft Patients.
Unilateral cleft lip and palate (UCLP) affects nasal function and appearance. There is a lack of objective measurements to evaluate these features. This study analyzes whether objective measurements on photographs correlate with nasal function and/or appearance among adults treated for UCLP. All patients with UCLP born from 1960 to 1987 treated at the Uppsala University Hospital were invited (n = 109). Participation rate was 68% (n = 74); mean follow-up was 35 years. An age-matched control group (n = 61) underwent the same tests. Nostril area, nasal tip deviation angle, and width of the nostril were measured on photographs and were compared with functional tests and with appearance as assessed by self-assessment questionnaire, professional panel, or laymen panel. The photographically measured nostril area correlated with nasal volume (acoustic rhinometry) among UCLP patients, both cleft side and noncleft side, and controls (0.331, P = 0.005; 0.338, P = 0.004; and 0.420, P < 0.001, respectively). For the patients' noncleft side and controls, the area correlated inversely with airflow resistance at inspiration (noncleft side: -0.245, P = 0.043; controls: -0.226, P = 0.013). Laymen assessment of nasal appearance correlated with width ratio of the patients (0.27, P = 0.022) and with nasal tip deviation angle and area ratio of the controls (0.26, P = 0.041, and 0.31, P = 0.015, respectively). Photographic measurements correlate partially with both functional tests of the nose and panel ratings of appearance. No correlation was found with self-assessment of appearance. Evaluation of photographs needs to be combined with patient-reported outcome measures to be a valuable endpoint of nasal appearance.


Vertical-cavity saturable-absorber intensity modulator.
We propose and demonstrate a reflection-type optical modulator, with surface-normal architecture, that exploits the optical saturation of absorption in semiconductor quantum wells. The modulation section of the modulator, which is composed of quantum wells placed within a Fabry-Perot cavity, is optically controlled by an intensity-modulated beam generated by an in-plane laser integrated monolithically on the same wafer and grown in a single epitaxial step. The modulation section and the in-plane laser share the same medium; therefore, efficient coupling between the control beam and the signal beam is achieved. The device was successfully used for active mode locking of an erbium-doped fiber laser.


ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.
Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.


Transition from cyclosporine-induced renal dysfunction to nephrotoxicity in an in vivo rat model.
Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments (3 and 9 weeks, respectively). Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN) levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR) reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-β1), factor nuclear kappa B (NF-κβ) and Tumor Protein P53 (TP53) kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR) and the antigen identified by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy.


Distinguishing Two Types of Variability in a Sit-to-Stand Task.
Variability is commonly observed in complex behavior, such as the maintenance of upright posture. The current study examines the value added by using nonlinear measures of variability to identify dynamic stability instead of linear measures that reflect average fluctuations about a mean state. The largest Lyapunov exponent (λ1) and SD were calculated on mediolateral movement as participants performed a sit-to-stand task on a stable and unstable platform. Both measures identified changes in movement across postures, but results diverged when participants stood on the unstable platform. Large SD indicated an increase in movement variability, but small λ1 identified those movements as stable and controlled. The results suggest that a combination of linear and nonlinear analyses is useful in identifying the proportion of observed variability that may be attributed to structured, controlled sources. Nonlinear measures of variability, like λ1, can further be used to make predictions about transitions between stable postures and to identify a system's resistance to disruption from external perturbations. Those features make nonlinear analyses highly applicable to both human movement research and clinical practice.


Cost-utility analysis of surgical fixation with Kirschner wire versus casting after fracture of the distal radius : a health economic evaluation of the DRAFFT2 trial.
The aim of this study was to compare the cost-effectiveness of surgical fixation with Kirschner (K-)wire ersus moulded casting after manipulation of a fracture of the distal radius in an operating theatre setting. An economic evaluation was conducted based on data collected from the Distal Radius Acute Fracture Fixation Trial 2 (DRAFFT2) multicentre randomized controlled trial in the UK. Resource use was collected at three, six, and 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from an NHS and personal social services perspective. Sensitivity analyses were conducted to examine the robustness of cost-effectiveness estimates, and decision uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves. In the base case analysis, surgical fixation with K-wire was more expensive (£29.65 (95% confidence interval (CI) -94.85 to 154.15)) and generated lower QALYs (0.007 (95% CI -0.03 to 0.016)) than moulded casting, but this difference was not statistically significant. The probability of K-wire being cost-effective at a £20,000 per QALY cost-effectiveness threshold was 24%. The cost-effectiveness results remained robust in the sensitivity analyses. The findings suggest that surgical fixation with K-wire is unlikely to be a cost-effective alternative to a moulded cast in adults, following manipulation of a fracture of the distal radius in a theatre setting.Cite this article: Bone Joint J 2022;104-B(11):1225-1233.


Coping, drug use, and religiosity/spirituality in relation to HIV serostatus among gay and bisexual men.
Cross-sectional data were collected on a sample of 259 gay and bisexual, male-identified individuals as part of a larger study of the psychosocial functioning of lesbian, gay, bisexual, and transgender persons. Analyses considered differences between HIV-positive and HIV-negative men in relation to active and religious coping strategies; avoidant coping strategies (specifically, illicit drug use); and the psychosocial states of anxiety, hostility, and depression in relation to self-reported HIV-status of the participants. As compared with HIV-negative men, the HIV positive participants indicated a greater likelihood of engaging in illicit substance use within the previous 3 months, as well as higher levels of both active and religious coping strategies. Illicit substance use also was found to be related to higher levels of depression, anxiety, and hostility. A multivariate model indicated a significant difference in substance-based and active coping strategies among the men surveyed, with persons with a self-reported HIV-positive serostatus endorsing higher levels of both strategies. These results and their implications for prevention and future research are discussed, rooted in the understanding that a complex reality for coping is often enacted by HIV-positive men.


Neuropsychiatric Profile in Malaria: An Overview.
Malaria is the most important parasitic disease of humans causes clinical illness over 300-500 million people globally and over one million death every year globally. The involvement of the nervous system in malaria is studied in this paper, to help formulate a strategy for better malaria management. To study the Neuropsychiatric manifestation in malaria. This was a prospective observational study in 170 patients with a clinical diagnosis of malaria admitted in various medical wards of medicine department of PBM Hospital, Bikaner during epidemic of malaria. It included both sexes of all age groups except the paediatric range. The diagnosis of malaria was confirmed by examination of thick and thin smear/optimal test/strip test. Only those cases that had asexual form of parasite of malaria in the blood by smear examination or optimal test were included in the study. Out of total 170 patients 104 (62%) reported Plasmodium falciparum (PF), Plasmodium vivax (PV) were 57 (33.5%) followed by mixed (PF+PV) 9 (5.3%) cases. The total PBF-MP test positivity was 84.5%. Maximum patients were belonging to the age range of 21-40 year with male predominance. Neuropsychiatric manifestation seen in falciparum malaria (n=111) as follow: altered consciousness 20 (18.01%), headache 17 (15.32%), neck rigidity 5 (4.5%), convulsion 5 (4.55%), extra pyramidal rigidity 2 (1.8%), decorticate rigidity 1 (0.90%), decerebrate rigidity 1 (0.90%), cerebellar ataxia 3 (2.7%), subarachnoid haemorrhage 1 (0.90%), aphasia 2 (1.8%), subconjunctival haemorrhage 1 (0.90%), conjugate deviation of eye 1 (0.90%) and psychosis 6 (5.40%). Twenty one patients presented with cerebral malaria out of 111 patients. Most patients of cerebral malaria presented with altered level of consciousness followed by headache and psychosis. Acute confusional state with clouding of consciousness was the most common presentation of psychosis (50%). Neuropsychiatric manifestations are not an uncommon presentation of malaria. Most commonly caused by PF malaria. Malaria should be thought as a differential diagnosis in pyrexia with neuropsychiatric manifestation. Observation obtained in the study will be highly useful for the diagnosis and management of patients suffering from malaria.


Characterization of "Yaa Chud" Medicine on the Thailand-Myanmar border: selecting for drug-resistant malaria and threatening public health.
Multidrug-resistant Plasmodium falciparum malaria is a severe public health problem on the Thailand-Myanmar border. Many villagers buy packets of 4-5 mixed medicines ("yaa chud") from shops without medical assessment as their first-line malaria treatment. In 2000-2001 a local researcher purchased 50 yaa chud from 44 shops around Mae Sot, Thailand and Myawaddy, Myanmar (Burma), for his wife who was said to be pregnant with fever and drowsiness. The tablets/capsules were provisionally identified by appearance and active ingredients determined in a subset by using mass and atomic spectrometry. The most frequently detected active ingredients were acetaminophen (22%), chlorpheniramine (13.4%), chloroquine (12.6%), tetracycline/doxycycline (11.4%), and quinine (5.1%). Only seven bags contained potentially curative medicine for malaria. A total of 82% of the bags contained medicines contraindicated in pregnancy. Inappropriate, ineffective antimalarial drugs on the Thailand-Myanmar border are likely to increase malaria morbidity, mortality and health costs and engender the emergence and spread of antimalarial drug resistance.


Matching sender and receiver: poikilothermy and frequency tuning in a tree cricket.
Animals communicate in non-ideal and noisy conditions. The primary method they use to improve communication efficiency is sender-receiver matching: the receiver's sensory mechanism filters the impinging signal based on the expected signal. In the context of acoustic communication in crickets, such a match is made in the frequency domain. The males broadcast a mate attraction signal, the calling song, in a narrow frequency band centred on the carrier frequency (CF), and the females are most sensitive to sound close to this frequency. In tree crickets, however, the CF changes with temperature. The mechanisms used by female tree crickets to accommodate this change in CF were investigated at the behavioural and biomechanical level. At the behavioural level, female tree crickets were broadly tuned and responded equally to CFs produced within the naturally occurring range of temperatures (18 to 27°C). To allow such a broad response, however, the transduction mechanisms that convert sound into mechanical and then neural signals must also have a broad response. The tympana of the female tree crickets exhibited a frequency response that was even broader than suggested by the behaviour. Their tympana vibrate with equal amplitude to frequencies spanning nearly an order of magnitude. Such a flat frequency response is unusual in biological systems and cannot be modelled as a simple mechanical system. This feature of the tree cricket auditory system not only has interesting implications for mate choice and species isolation but may also prove exciting for bio-mimetic applications such as the design of miniature low frequency microphones.


Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer.
Overexpression of tumor-associated antigens (TAAs) has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was thus designed to test whether circulating antibody to p16 protein-derived antigens was altered in lung cancer. Two hundred seventy-one patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender, and smoking history were recruited in this study. The levels of circulating anti-p16 IgA and IgG antibodies were tested using an enzyme-linked immunosorbent assay (ELISA) developed in-house with linear peptide antigens derived from p16 protein. Student's t test showed that patients with NSCLC had a significant higher level of anti-p16 IgG antibody than control subjects (t = 2.74, P = 0.0063) but did not have a significant increase in IgA antibody levels (t = 1.92, P = 0.056). The sensitivity against >90% specificity was 19.7% for the IgG assay with an inter-assay deviation of 11.6%, and 10.3% for the IgA assay with an inter-assay deviation of 14.7%. Based on a cut-off value determined by the 99th percentile of control IgG levels, the anti-p16 IgG positivity was 6.7% in patients with NSCLC compared to 0.88% in control subjects (χ (2) = 10.58, P = 0.001, OR = 7.97, 95% CI 1.84–34.85). Circulating anti-p16 IgG levels were increased with stages of NSCLC, and patients with stage IV NSCLC had the highest IgG level among all four stages (t = 2.42, P = 0.016, compared with the control group). Pearson correlation analysis showed a significant correlation between circulating levels of IgA and IgG in the patient group (r = −0.2, df = 236, P = 0.0021) but not in the control group (r = −0.1, df = 205, P = 0.146). Circulating IgG antibody to p16 protein may be a potential biomarker with prognostic values for lung cancer.


Optimization of bioactive compounds in buckwheat sprouts and their effect on blood cholesterol in hamsters.
Nutrient levels in buckwheats that were maximized in day 8 sprouts (D8SP) included total phenolics, quercetin, and l-ascorbic acid, whereas those of oxalic, malic, tartaric, and citric acids, rutin, and gamma-aminobutyric acid (GABA) were found to reach maximum levels on day 10. Ethanolic extract of D8SP (2.5 mg/mL) revealed potent free-radical scavenging (FRS) and antioxidative (ANO) capabilities. However, its Fe2+-chelating capability was only moderate. To further study the hypolipidemic activity of D8SP, 36 Syrian hamsters were grouped into six groups and fed for 28 days, respectively, with (i) control meal, (ii) high fat plus high cholesterol meal, (iii) high fat plus high cholesterol plus 2.5% of buckwheat seeds, (iv) high fat plus high cholesterol plus 25% of buckwheat seeds, (v) high fat plus high cholesterol plus 2.5% of D8SP, and (vi) high fat plus high cholesterol plus 25% of D8SP. High seed meal prominently enhanced body weight gain, whereas high sprout meal exhibited the highest feed efficiency. Ratios of liver/body weight (L/B) were significantly lowered by all BS meals. Although low seed meal reduced serum total cholesterol (TC) levels (p<0.05), its effect was still inferior to the high seed and sprout meals (p<0.01). In contrast, serum triglyceride (TG) levels were lowered only by the high seed and sprout meals (p<0.05). Alternatively, levels of serum low-density lipoprotein cholesterol (LDL-C) were significantly suppressed by all buckwheat meals (p<0.01). Serum high-density lipoprotein cholesterol (HDL-C) levels were increased, however, insignificantly. Nutraceutically more meaningful is that both LDL-C/HDL-C and TC/HDL-C ratios were significantly lowered (p<0.01). Apparently, hepatic TC levels were significantly reduced, whereas hepatic TG levels were totally unaffected. Conclusively, sprouting triggers a variety of nutritional changes in buckwheats. Day 8 sprouts, consisting of high polyphenolic and moderate quercetin contents, are nutraceutically maximized when hypocholesterolemic, hypotriglyceridemic, and antioxidative activities are concerned.


5SRNAdb: an information resource for 5S ribosomal RNAs.
Ribosomal 5S RNA (5S rRNA) is the ubiquitous RNA component found in the large subunit of ribosomes in all known organisms. Due to its small size, abundance and evolutionary conservation 5S rRNA for many years now is used as a model molecule in studies on RNA structure, RNA-protein interactions and molecular phylogeny. 5SRNAdb (http://combio.pl/5srnadb/) is the first database that provides a high quality reference set of ribosomal 5S RNAs (5S rRNA) across three domains of life. Here, we give an overview of new developments in the database and associated web tools since 2002, including updates to database content, curation processes and user web interfaces.


ADFCNN: Attention-Based Dual-Scale Fusion Convolutional Neural Network for Motor Imagery Brain-Computer Interface.
Convolutional neural networks (CNNs) have been successfully applied to motor imagery (MI)-based brain-computer interface (BCI). Nevertheless, single-scale CNN fail to extract abundant information over a wide spectrum from EEG signals, while typical multi-scale CNNs cannot effectively fuse information from different scales with concatenation-based methods. To overcome these challenges, we propose a new scheme equipped with attention-based dual-scale fusion convolutional neural network (ADFCNN), which jointly extracts and fuses EEG spectral and spatial information at different scales. This scheme also provides novel insight through self-attention for effective information fusion from different scales. Specifically, temporal convolutions with two different kernel sizes identify EEG μ and β rhythms, while spatial convolutions at two different scales generate global and detailed spatial information, respectively, and the self-attention mechanism performs feature fusion based on the internal similarity of the concatenated features extracted by the dual-scale CNN. The proposed scheme achieves the superior performance compared with state-of-the-art methods in subject-specific motor imagery recognition on BCI Competition IV dataset 2a, 2b and OpenBMI dataset, with the cross-session average classification accuracies of 79.39% and significant improvements of 9.14% on BCI-IV2a, 87.81% and 7.66% on BCI-IV2b, 65.26% and 7.2% on OpenBMI dataset, and the within-session average classification accuracies of 86.87% and significant improvements of 10.89% on BCI-IV2a, 87.26% and 8.07% on BCI-IV2b, 84.29% and 5.17% on OpenBMI dataset, respectively. What is more, ablation experiments are conducted to investigate the mechanism and demonstrate the effectiveness of the dual-scale joint temporal-spatial CNN and self-attention modules. Visualization is also used to reveal the learning process and feature distribution of the model.


How useful are Primary Trauma Care courses in sub-Saharan Africa?
More than five million deaths occur each year from injury with the vast majority occurring in low and middle-income countries (LMICs). Africa bears the highest road traffic related mortality rates in the world. Despite this, formal training in trauma management is not widely adopted in these countries. We report our results of 10 consecutive Primary Trauma Care (PTC) courses delivered in seven East and Central African countries, as part of the COSECSA Oxford Orthopaedic Link (COOL) initiative. Candidate's knowledge and clinical confidence in trauma management were assessed using a multiple-choice questionnaire and a confidence matrix rating of eight clinical scenarios. We performed descriptive statistical analysis on knowledge and clinical confidence scores of candidates before and after the course. We sub-analysed these scores, examining specifically the difference that exist between gender, job-roles and instructors versus non-instructors. We have trained 345 new PTC providers and 99 new PTC instructors over the 10 courses. Data sets were complete for 322 candidates. Just under a third of candidates were women (n=94). Over two-thirds of candidates (n=240) were doctors, while the remainder comprised of nurses, medical students and clinical officers. Overall, the median pre-course MCQ score was 70% which increased to 87% post course (p<0.05). Men achieved a higher MCQ score both pre- and post-course compared to women (p<0.05); however there was no significant difference in the degree of improvement of MCQ scores between gender. Instructors outperform non-instructors (p<0.05), and similarly doctors outperform non-doctors on final MCQ scores (post-course). However, it was the non-doctors who showed a statistically significant improvement in scores before and after the course (20% non-doctors vs 16% doctors, p<0.05). Candidate's clinical confidence also demonstrated significant improvement following the course (p<0.05). Our work demonstrates that COOL-funded PTC courses in the COSECSA region delivered to front-line health staff have helped improve their knowledge and confidence in trauma management, irrespective of their job-roles and gender. Further follow-up is needed to establish the long-term impact of PTC courses in this region.


Same-sex attraction, social relationships, psychosocial functioning, and school performance in early adolescence.
The authors examined whether 13- to 15-year-old adolescents who experience feelings of same-sex attraction (SSA) differ from those without such feelings in the quality of relationships with parents, peers, and class mentors and in psychosocial functioning (health status and school performance). The authors also assessed whether differences in psychosocial functioning resulted from differences in the quality of social relationships. Data were collected from 866 Dutch high school students (mean age 13.61 years) by means of a computer-based questionnaire. Of the participants, 74 (8.5%) reported having feelings of SSA. The participants with SSA rated the quality of their relationships with their fathers and their peers lower than did those without SSA. Participants with SSA also had poorer mental health (higher levels of depression and lower levels of self-esteem) and lower school performance. A mediation analysis revealed that differences in psychosocial functioning resulted from differences in the quality of the same-sex attracted youths' social relationships, especially with fathers and peers.


Denitrification as the dominant nitrogen loss process in the Arabian Sea.
Primary production in over half of the world's oceans is limited by fixed nitrogen availability. The main loss term from the fixed nitrogen inventory is the production of dinitrogen gas (N(2)) by heterotrophic denitrification or the more recently discovered autotrophic process, anaerobic ammonia oxidation (anammox). Oceanic oxygen minimum zones (OMZ) are responsible for about 35% of oceanic N(2) production and up to half of that occurs in the Arabian Sea. Although denitrification was long thought to be the only loss term, it has recently been argued that anammox alone is responsible for fixed nitrogen loss in the OMZs. Here we measure denitrification and anammox rates and quantify the abundance of denitrifying and anammox bacteria in the OMZ regions of the Eastern Tropical South Pacific and the Arabian Sea. We find that denitrification rather than anammox dominates the N(2) loss term in the Arabian Sea, the largest and most intense OMZ in the world ocean. In seven of eight experiments in the Arabian Sea denitrification is responsible for 87-99% of the total N(2) production. The dominance of denitrification is reproducible using two independent isotope incubation methods. In contrast, anammox is dominant in the Eastern Tropical South Pacific OMZ, as detected using one of the isotope incubation methods, as previously reported. The abundance of denitrifying bacteria always exceeded that of anammox bacteria by up to 7- and 19-fold in the Eastern Tropical South Pacific and Arabian Sea, respectively. Geographic and temporal variability in carbon supply may be responsible for the different contributions of denitrification and anammox in these two OMZs. The large contribution of denitrification to N(2) loss in the Arabian Sea indicates the global significance of denitrification to the oceanic nitrogen budget.


[Pyogenic liver abscess--report of 72 cases].
Seventy-two patients with pyogenic liver abscess treated from Jan. 1986 through June 1988 were reviewed retrospectively. The average age was 55 years with a male to female ratio of 1.4:1. Most patients presented with the typical fever, chills and RUQ pain, but unusual signs and symptoms were also common. The right lobe was more commonly involved than left lobe. Biliary tract stone was the most frequent etiology (44.4%) and association with DM was common (37.5%). An elevated alkaline phosphatase and leukocytosis were useful clues to a liver abscess, but diagnosis depended on imaging of an abscess cavity either by echo or CT scan. The average time from onset of Symptoms to diagnosis was 9.3 days and a delay in diagnosis by the doctors was common. The most common complication was septicemia and factors with poor prognosis were old age (greater than or equal to 60 yrs), septicemia, cancer, peritonitis, and serum bilirubin greater than or equal to 5 mg/dl. The overall mortality was 29% with no difference between the group with surgical drains (28.5%) and the group with percutaneous transhepatic aspiration or drains (29.4%).


Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries.
One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient.


Evaluation of ultrasonography guidance for single-puncture temporomandibular joint arthrocentesis: A randomized clinical study.
Objective To evaluate ultrasonography (US) guidance on the single-puncture temporomandibular joint (TMJ) arthrocentesis technique. Methods Twenty-four patients were randomly divided into two groups (n = 12 in each group), and single puncture arthrocentesis (SPA) was performed with and without US guidance in groups 1 and 2. During the one-year follow-up period, the groups were statistically evaluated by the visual analog scale for pain, maximum mouth opening, lateral excursion, and protrusion within each group and between the two groups. Results Both treatment groups showed significant improvement, compared to the baseline levels for almost all outcome variables. However, there were no statistically significant differences between groups 1 and 2 (p > 0.05). Conclusion US guidance can be used for cannula placement in SPA. However, the outcome results are the same with or without its use.