DNA methylation in clonal duckweed (Lemna minor L.) lineages reflects current and historical environmental exposures.
Environmentally induced DNA methylation variants may mediate gene expression responses to environmental changes. If such induced variants are transgenerationally stable, there is potential for expression responses to persist over multiple generations. Our current knowledge in plants, however, is almost exclusively based on studies conducted in sexually reproducing species where the majority of DNA methylation changes are subject to resetting in germlines, limiting the potential for transgenerational epigenetics stress memory. Asexual reproduction circumvents germlines, and may therefore be more conducive to long-term inheritance of epigenetic marks. Taking advantage of the rapid clonal reproduction of the common duckweed Lemna minor, we hypothesize that long-term, transgenerational stress memory from exposure to high temperature can be detected in DNA methylation profiles. Using a reduced representation bisulphite sequencing approach (epiGBS), we show that temperature stress induces DNA hypermethylation at many CG and CHG cytosine contexts but not CHH. Additionally, differential methylation in CHG context that was observed was still detected in a subset of cytosines, even after 3-12 generations of culturing in a common environment. This demonstrates a memory effect of stress reflected in the methylome and that persists over multiple clonal generations. Structural annotation revealed that this memory effect in CHG methylation was enriched in transposable elements. The observed epigenetic stress memory is probably caused by stable transgenerational persistence of temperature-induced DNA methylation variants across clonal generations. To the extent that such epigenetic memory has functional consequences for gene expression and phenotypes, this result suggests potential for long-term modulation of stress responses in asexual plants.


Should a colon cancer screening decision aid include the option of no testing? A comparative trial of two decision aids.
An important question in the development of decision aids about colon cancer (CRC) screening is whether to include an explicit discussion of the option of not being screened. We examined the effect of including or not including an explicit discussion of the option of deciding not to be screened in a CRC screening decision aid on subjective measures of decision aid content; interest in screening; and knowledge. Adults ages 50-85 were assigned to view one of two versions of the decision aid. The two versions differed only in the inclusion of video segments of two men, one of whom decided against being screened. Participants completed questionnaires before and after viewing the decision aid to compare subjective measures of content, screening interest and intent, and knowledge between groups. Likert response categories (5-point) were used for subjective measures of content (eg. clarity, balance in favor/against screening, and overall rating), and screening interest. Knowledge was measured with a three item index and individual questions. Higher scores indicated favorable responses for subjective measures, greater interest, and better knowledge. For the subjective balance, lower numbers were associated with the impression of the decision aid favoring CRC screening. 57 viewed the "with" version which included the two segments and 49 viewed the "without" version. After viewing, participants found the "without" version to have better subjective clarity about benefits of screening ("with" 3.4, "without" 4.1, p < 0.01), and to have greater clarity about downsides of screening ("with" 3.2, "without" 3.6, p = 0.03). The "with" version was considered to be less strongly balanced in favor of screening. ("with" 1.8, "without" 1.6, p = 0.05); but the "without" version received a better overall rating ("with" 3.5, "without" 3.8, p = 0.03). Groups did not differ in screening interest after viewing a decision aid or knowledge. A decision aid with the explicit discussion of the option of deciding not to be screened appears to increase the impression that the program was not as strongly in favor of screening, but decreases the impression of clarity and resulted in a lower overall rating. We did not observe clinically important or statistically significant differences in interest in screening or knowledge.


Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.
Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the "endophenotype" common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum "endophenotype." It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.


Turbulent mixing under drifting pack ice in the weddell sea.
By providing cold, dense water that sinks and mixes to fill the abyssal world ocean, high-latitude air-sea-ice interaction is the main conduit through which the deep ocean communicates with the rest of the climate system. A key element in modeling and predicting oceanic impact on climate is understanding the processes that control the near surface exchange of heat, salt, and momentum. In 1992, the United States-Russian Ice Station Weddell-1 traversed the western Weddell Sea during the onset of winter, providing a platform for direct measurement of turbulent heat flux and Reynolds stress in the upper ocean. Data from a storm early in the drift indicated (i) well-formed Ekman spirals (in both velocity and turbulent stress); (ii) high correlation between mixed layer heat flux and temperature gradients; (iii) that eddy viscosity and eddy thermal diffusivity were similar, about 0.02 square meters per second; and (iv) that the significant turbulent length scale (2 to 3 meters through most of the boundary layer) was proportional to the wavelength at the peak in the weighted vertical velocity spectrum. The measurements were consistent with a simple model in which the bulk eddy viscosity in the neutrally buoyant mixed layer is proportional to kinematic boundary stress divided by the Coriolis parameter.


Seewis virus: phylogeography of a shrew-borne hantavirus in Siberia, Russia.
Hantaviral antigens were originally reported more than 20 years ago in tissues of the Eurasian common shrew (Sorex araneus), captured in European and Siberian Russia. The recent discovery of Seewis virus (SWSV) in this soricid species in Switzerland provided an opportunity to investigate its genetic diversity and geographic distribution in Russia. Lung tissues from 45 Eurasian common shrews, 4 Laxmann's shrews (Sorex caecutiens), 3 Siberian large-toothed shrews (Sorex daphaenodon), 9 pygmy shrews (Sorex minutus), 28 tundra shrews (Sorex tundrensis), and 6 Siberian shrews (Crocidura sibirica), captured in 11 localities in Western and Eastern Siberia during June 2007 to September 2008, were analyzed for hantavirus RNA by reverse transcription-polymerase chain reaction. Hantavirus L and S segment sequences, detected in 11 S. araneus, 2 S. tundrensis, and 2 S. daphaenodon, were closely related to SWSV, differing from the prototype mp70 strain by 16.3-20.2% at the nucleotide level and 1.4-1.7% at the amino acid level. Alignment and comparison of nucleotide and amino acid sequences showed an intrastrain difference of 0-11.0% and 0% for the L segment and 0.2-8.5% and 0% for the S segment, respectively. Phylogenetic analysis, using neighbor-joining, maximum-likelihood, and Bayesian methods, showed geographic-specific clustering of SWSV strains in Western and Eastern Siberia. This is the first definitive report of shrew-borne hantaviruses in Siberia, and demonstrates the impressive distribution of SWSV among phylogenetically related Sorex species. Coevolution and local adaptation of SWSV genetic variants in specific chromosomal races of S. araneus may account for their geographic distribution.


"You Don't Have a Normal Life": Coping with Chagas Disease in Los Angeles, California.
Chagas disease is the neglected tropical disease of greatest public health impact in the United States, where it affects over 300,000 people. Diverse barriers limit healthcare access for affected people; fewer than 1% have obtained testing or treatment. We interviewed 50 people with Chagas disease in Los Angeles, California, and administered a cultural consensus analysis questionnaire. Participants were asked about their experiences and perceptions of Chagas disease, access to healthcare, and strategies for coping with the disease. In participants' narratives, the physical and emotional impacts of the disease were closely interwoven. Participant explanatory models highlight difficulties in accessing care, despite a desire for biomedical treatment. Obtaining testing and treatment for Chagas disease poses substantial challenges for US patients.


Decadal evolution of the surface energy budget during the fast warming and global warming hiatus periods in the ERA-interim.
The global-mean surface temperature has experienced a rapid warming from the 1980s to early-2000s but a muted warming since, referred to as the global warming hiatus in the literature. Decadal changes in deep ocean heat uptake are thought to primarily account for the rapid warming and subsequent slowdown. Here, we examine the role of ocean heat uptake in establishing the fast warming and warming hiatus periods in the ERA-interim through a decomposition of the global-mean surface energy budget. We find the increase of carbon dioxide alone yields a nearly steady increase of the downward longwave radiation at the surface from the 1980s to the present, but neither accounts for the fast warming nor warming hiatus periods. During the global warming hiatus period, the transfer of latent heat energy from the ocean to atmosphere increases and the total downward radiative energy flux to the surface decreases due to a reduction of solar absorption caused primarily by an increase of clouds. The reduction of radiative energy into the ocean and the surface latent heat flux increase cause the ocean heat uptake to decrease and thus contribute to the slowdown of the global-mean surface warming. Our analysis also finds that in addition to a reduction of deep ocean heat uptake, the fast warming period is also driven by enhanced solar absorption due predominantly to a decrease of clouds and by enhanced longwave absorption mainly attributed to the air temperature feedback.


'It's your life!': injecting drug users, individual responsibility and hepatitis C prevention.
Health promotion materials on hepatitis C prevention and safe injecting enjoin injecting drug users to produce ethical selves through relatively rigid social and hygiene-related conduct. This article examines a sample of safe injecting and hepatitis C prevention health promotion materials, and interview data gathered from injecting drug users, to consider the ways in which the notion of individual responsibility functions within them. I argue that the primacy of the individual in western culture is indeed reflected in hepatitis C and safe injecting materials and, that for a range of reasons, injecting drug users also make use of notions of individual responsibility. The article concludes by considering the social and health implications of this individualist approach to injecting drug use and health promotion, and by suggesting ways in which effective materials which do not focus solely on the individual can be created.


Intraoperative Meditation Music as an Adjunct to Subarachnoid Block for the Improvement of Postoperative Outcomes Following Cesarean Section: A Randomized Placebo-controlled Comparative Study.
Music therapy is a nonpharmacological modality which can provide promising results for postcesarean section recovery. The aim of this study was to compare the effects of two types of intraoperative meditation music with control group on postcesarean section pain, anxiety, nausea, vomiting, and psychological maternal wellbeing. A prospective, randomized, controlled study was conducted on 189 patients. The inclusion criteria were the American Society of Anaesthesiologists physical status classes 1E and 2E women aged over 18 years posted for emergency cesarean section under spinal anesthesia. The exclusion criteria were patients with hearing/ear abnormalities and psychiatric disorders. Patients were randomly allocated into three groups - soothing meditation music (M) group, binaural beat meditation music (B) group, and control (C) group - where no music was played. After intervention, data were collected and statistically analyzed. Student's t-test was applied for calculation of normative distribution and Mann-Whitney U-test for nonnormative distribution. Nominal categorical data between the groups were compared using Chi-squared test. P <0.05 indicated a statistically significant difference. Both intraoperative meditation music groups had statistically significant less postoperative pain and anxiety and a better overall psychological wellbeing as compared to the control. There was no statistically significant difference in the occurrence and severity of postoperative nausea and vomiting across all three groups. Intraoperative meditation music as good adjunct to spinal anesthesia can improve a cesarean section patient's postoperative experience by reducing postoperative pain, anxiety, and psychological wellbeing.


Comparing Small Area Fair Market Rents With Other Rental Measures Across Diverse Housing Markets.
Small Area Fair Market Rents (SAFMRs) are calculated at the 40th percentile of the U.S. postal ZIP Code instead of the metropolitan area in an effort to capture localized rents to expand choice for voucher holders to access housing in higher-opportunity neighborhoods. Existing studies on the potential and actual outcomes of SAFMRs demonstrate that findings vary for different types of housing markets. Furthermore, the decisions public housing authorities (PHAs) make in the implementation process affect PHAs' program budget and the rent burden and locational outcomes for voucher households. This study aims to address how these implementation factors are affected by local rental market conditions for three PHAs-Housing Authority of the City of Fort Lauderdale, San Antonio Housing Authority, and Seattle Housing Authority-in diverse housing markets. By comparing different sources of market rent estimates with SAFMRs in each location, we contribute new information about how this rule is likely to produce different residential outcomes in terms of increased access to low-poverty neighborhoods and adjustments to payment standards in low-rent neighborhoods. The findings reveal differences across rent measures in terms of estimated levels and relative differences across ZIP Codes. These findings suggest that housing authorities may face challenges in meeting the objectives of the SAFMR final rule without some form of local adjustments.


Vibration arthrometry in congenital dislocation of the hip.
Three hundred six neonates referred to a research clinic for vibration arthrometry were studied to determine whether the application of objective methods could enhance the accuracy of hip examinations. A total of 629 vibration episodes (hip "clicks" and "clunks") were detected using miniature accelerometers and recorded during testing for congenital dislocation of the hip. Five categories of congenital dislocations of the hip (CDH) were defined: normal (53 cases), safe click (201 cases), click associated with later CDH (16 cases), unstable (14 cases), and late CDH (22 cases). Follow-up examinations were performed over a four-year period. Detailed measurement of vibration signals was possible and resulted in the resolution of eight variables for each episode. Two variables, pulse area and peak frequency, were selected for their power to discriminate between the five clinical groups. The pulse area values were higher for the late and unstable groups. In addition, the vibrations were examined using Fourier analysis, and the safe click group demonstrated higher frequency components than any other group. Vibration arthrometry is proposed as a possible adjunct in screening for CDH, as it may pick up cases that would be missed by an average examiner and it could monitor clicks, thus avoiding nonessential splintage.


Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000-2011.
Guidelines to treat acute otitis media (AOM) were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure. Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year. We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%. In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections.


Superior sensory, motor, and cognitive performance in elderly individuals with multi-year dancing activities.
Aging is associated with a progressive decline of mental and physical abilities. Considering the current demographic changes in many civilizations there is an urgent need for measures permitting an independent lifestyle into old age. The critical role of physical exercise in mediating and maintaining physical and mental fitness is well-acknowledged. Dance, in addition to physical activity, combines emotions, social interaction, sensory stimulation, motor coordination and music, thereby creating enriched environmental conditions for human individuals. Here we demonstrate the impact of multi-year (average 16.5 years) amateur dancing (AD) in a group of elderly subjects (aged 65-84 years) as compared to education-, gender- and aged-matched controls (CG) having no record of dancing or sporting activities. Besides posture and balance parameters, we tested reaction times, motor behavior, tactile and cognitive performance. In each of the different domains investigated, the AD group had a superior performance as compared to the non-dancer CG group. Analysis of individual performance revealed that the best participants of the AD group were not better than individuals of the CG group. Instead, the AD group lacked individuals showing poor performance, which was frequently observed for the CG group. This observation implies that maintaining a regular schedule of dancing into old age can preserve cognitive, motor and perceptual abilities and prevent them from degradation. We conclude that the far-reaching beneficial effects found in the AD group make dance, beyond its ability to facilitate balance and posture, a prime candidate for the preservation of everyday life competence of elderly individuals.


Low-cost portable fluorescein angiography.
Fundus fluorescein angiography has great potential as a unique non-invasive tool to investigate in vivo the microvascular pathogenesis of a wide variety of diseases affecting the central nervous system. However, because it requires a bulky and expensive tabletop retinal camera, it is normally limited to cooperative and alert seated patients in well-resourced settings. Recently completed and ongoing studies of the pathogenesis of severe malaria are using fluorescein angiography to examine in detail the postulated central role of microvascular obstruction. We describe a novel method of fluorescein angiography with a portable retinal camera that can be adapted at very low cost for use in sick patients at the bedside. This method greatly expands the scope of potential studies utilising fluorescein angiography.


Probabilistic models for semisupervised discriminative motif discovery in DNA sequences.
Methods for discriminative motif discovery in DNA sequences identify transcription factor binding sites (TFBSs), searching only for patterns that differentiate two sets (positive and negative sets) of sequences. On one hand, discriminative methods increase the sensitivity and specificity of motif discovery, compared to generative models. On the other hand, generative models can easily exploit unlabeled sequences to better detect functional motifs when labeled training samples are limited. In this paper, we develop a hybrid generative/discriminative model which enables us to make use of unlabeled sequences in the framework of discriminative motif discovery, leading to semisupervised discriminative motif discovery. Numerical experiments on yeast ChIP-chip data for discovering DNA motifs demonstrate that the best performance is obtained between the purely-generative and the purely-discriminative and the semisupervised learning improves the performance when labeled sequences are limited.


Weight loss as a predictor of cancer and serious disease in primary care: an ISAC-approved CPRD protocol for a retrospective cohort study using routinely collected primary care data from the UK.
Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when general practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. A retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: (1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; (2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients > 18 years and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage, and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.


The impact of microglial activation on blood-brain barrier in brain diseases.
The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders.


A forward genetic screen reveals novel independent regulators of ULBP1, an activating ligand for natural killer cells.
Recognition and elimination of tumor cells by the immune system is crucial for limiting tumor growth. Natural killer (NK) cells become activated when the receptor NKG2D is engaged by ligands that are frequently upregulated in primary tumors and on cancer cell lines. However, the molecular mechanisms driving NKG2D ligand expression on tumor cells are not well defined. Using a forward genetic screen in a tumor-derived human cell line, we identified several novel factors supporting expression of the NKG2D ligand ULBP1. Our results show stepwise contributions of independent pathways working at multiple stages of ULBP1 biogenesis. Deeper investigation of selected hits from the screen showed that the transcription factor ATF4 drives ULBP1 gene expression in cancer cell lines, while the RNA-binding protein RBM4 supports ULBP1 expression by suppressing a novel alternatively spliced isoform of ULBP1 mRNA. These findings offer insight into the stress pathways that alert the immune system to danger.


Fracture strength of indirect resin composite laminates to teeth with existing restorations: an evaluation of conditioning protocols.
This study evaluated the fracture strength and failure types of indirect resin-based composite laminates bonded to teeth with aged Class III composite restorations that were conditioned according to various protocols. Maxillary central incisors (N = 60) with window-type preparations received laminates made of a highly-filled resin composite material (Estenia) (10 per group).On the mesial and distal side, Class III cavities (3 x 3 mm) were prepared using ultrasonic burs and filled with resin composite (Quadrant Anterior Shine). The unrestored teeth served as a control group (group 6). All restored teeth (n=50) were thermocycled (5 degrees C to 55 degrees C, 6000X) and subjected to one of the conditioning protocols: (1) air-particle abrasion with alumina particles coated with silica (30-microm SiO2, CoJet)+silanization, (2) air-particle abrasion with alumina particles (50 microm, Al2O3)+silanization, (3) 9.5% hydrofluoric acid (HF) for 90 s (Ultradent)+silanization and (4) protocol of Clearfil Repair Kit, (5) adhesive resin (Quadrant Unibond Sealer). A three-step bonding procedure and dual-polymerizing resin cement (Panavia F 2.0) were employed. The inner surfaces of the laminates were conditioned (CoJet-Sand, 30 mum SiO2) and silanized (ESPE-Sil). All specimens were stored in water at 37 degrees C for one month prior to the fracture test. A significant difference was observed in fracture strength values between the groups (ANOVA, p = 0.0261). The only significant difference was between group 2 (299 +/- 103 N) and group 3 (471 +/- 126 N) (p = 0.0239) (Tukey's test, alpha = 0.05). The majority of failures were type C (35/60) (chipping of the laminate with enamel exposure), followed by type B (21/60) (cohesive failure within the composite laminate). The fracture strengths of the laminates tested did not show significant differences, whether they were bonded to existing, aged Class III composite restorations or to intact teeth. The failure types, however, varied between the groups. The lowest strengths were obtained from the air-particle abraded (50 microm, Al2O3) and silanized group.


Exposure to Mycophenolate and Fatherhood.
Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA. We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway. During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53). Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.


Anterior subluxation of the cervical spine: hyperflexion sprain.
Anterior subluxation (hyperflexion sprain) is localized, purely ligamentous disruption of the cervical spine caused by a limited flexion force. When associated with a simple wedge fraction, also a flexion injury, anterior subluxation may be the more significant lesion. Radiographically, anterior subluxation is characterised by (1) a localized kyphotic angulation at the level of injury; (2) anterior rotation, or displacement, of the subluxed vertebra; (3) anterior narrowing and posterior widening of the disc space; (4) widening of the space between the subluxed vertebral body and the subjacent articular masses; (5) displacement of the inferior articulating facets of the subluxed vertebra with respect to their contiguous subjacent facets; and (6) widening of the interspinous space ("fanning"). The localized kyphotic angulation at the level of ligamentous disruption distinguishes pathologic anterior subluxation from diffuse "reversal of the normal cervical lordosis"; produced by voluntary positioning or muscle spasm. Anterior subluxation is clinically significant because of the approximate 20% incidence of delayed instability due to impaired ligamentous healing.


Effect of selected alcohol dehydrogenase inhibitors on the human heart lactate dehydrogenase activity--an in vitro study.
Metabolic acidosis complicates methanol, ethylene glycol and other alcohol intoxications. It is caused firstly by acid metabolites and secondly by the lactate elevation. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH; EC 220.127.116.11) inhibitors and substrates: 4-methylpyrazole (4-MP), cimetidine, EDTA, ethanol and methanol on lactate dehydrogenase (LDH; EC 184.108.40.206) activity. The activity of LDH was determined spectrophotometrically in in vitro human heart homogenates with the mentioned compounds at 0.01, 0.1, 1.0 mM concentrations of 4-MP, cimetidine, EDTA, and 12.5, 25.0, 50.0 mM of ethanol and methanol. The LDH activity was significantly inhibited by 0.1 mM (p<0.05) and 1.0 mM (p<0.01) 4-MP and 1.00 mM EDTA (p<0.05). Higher LDH activity vs. control was observed in the samples incubated with all studied ethanol and methanol concentrations but these differences were not statistically significant. Thus, 4-MP was found to be the most effective inhibitor of LDH of all compounds tested. Therefore, such effect of 4-MP seems to be an additional advantage in methanol and ethylene glycol intoxications.


Length of esophageal cancer and degree of luminal stenosis during upper endoscopy predict T stage by endoscopic ultrasound.
Endoscopic ultrasonography (EUS) is considered to be the most accurate modality for T staging of esophageal cancer. This study attempted to determine whether endoscopic features such as the length and degree of luminal stenosis in esophageal cancer can predict the T stage on EUS. Thirty-five patients with newly diagnosed esophageal adenocarcinoma or squamous-cell carcinoma undergoing EUS prior to initiation of any treatment were included in the study. The length of the tumor was assessed prospectively during esophagogastroduodenoscopy (EGD) before EUS in 22 patients. Radial EUS was then performed in these patients. The other 13 patients had sufficient luminal stenosis to prevent complete advancement of the echo endoscope through the tumor. In these 13 patients, the length of the esophageal cancer was not examined, but the T and N stage up to the level of maximum advancement of the echo endoscope through the tumor were noted. All 13 patients with luminal stenosis had at least a T3 (n = 12) or T4 (n = 1) lesion up to the level of maximum advancement of the echo endoscope. Among the 22 patients in whom the length of the esophageal cancer was measured, the mean length in the 13 patients with a T1 or T2 lesion on EUS was 2.6 cm. The mean length in the nine patients with T3 esophageal cancer was 7.1 cm. The difference in the mean length of T1 or T2 lesions (2.6 cm) was significantly different ( P < 0.001) from the mean length of T3 lesions (7.1 cm). Using a clinical diagnostic testing approach, when > or = 5 cm length was used as a criteria for diagnosing T3 lesions, the sensitivity was 89 %, specificity 92 %, positive predictive value 89 %, and negative predictive value 92 %. There was also a suggestion of increased chances of lymph-node metastases with increasing length of esophageal cancer. In esophageal carcinoma, endoscopic features such as the length of the cancer and the degree of luminal stenosis correlate with T staging on EUS. Esophageal cancers that are > or = 5 cm in length, or are sufficiently stenotic to prevent passage of an endoscope, are much more likely to be T3 or higher-stage lesions, while those that are < 5 cm in length have a greater chance (92 %) of being T1 or T2.


The Cash and Counseling model of self-directed long-term care: Effectiveness with young adults with disabilities.
Young adults with disabilities face numerous barriers to independence and achieving markers of adulthood. Qualitative evidence suggests that flexible, self-directed budgets for purchasing home and community-based services might help fill an identified service gap and help improve the transition to adulthood for this group. Our aim was to evaluate the effectiveness of the Cash and Counseling model of self-directed budgets for young adults with long-term care disabilities by analyzing secondary data from the Cash and Counseling Demonstration and Evaluation randomized control trial. We compared nine-month community involvement, satisfaction rating, health status rating compared to peers, and unmet needs outcomes using bivariate and multivariate logistic regression. Our sample included 456 participants aged 18 to 30 randomized to treatment groups with the opportunity to receive Cash and Counseling (n = 207) or control groups eligible for agency-based care (n = 249), whether self-reported (n = 128) or by proxy (n = 328). Multivariate logistic regression models showed that compared to controls at nine-month follow-up, treatment group members had significantly greater odds of being very satisfied with life, when care was received, the care arrangement, transportation, help around the house and community, personal care, and getting along with paid attendants, and significantly lower odds of unmet needs with medication and routine health care at home and with transportation. Cash and Counseling performed better than or comparable with agency-based care for young adults with long-term care disabilities, suggesting its viability as a service option for this population.


Coffee consumption and the risk of cutaneous melanoma: a meta-analysis.
Results from epidemiologic studies on coffee consumption and the risk of cutaneous melanoma are inconsistent. We conducted a meta-analysis to assess the associations between the consumption of total coffee, caffeinated coffee and decaffeinated coffee and the risk of cutaneous melanoma, respectively. A literature search was performed in PubMed, Web of Science and EMBASE for relevant articles published up to August 2015. Pooled relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. Dose-response relationship was assessed by restricted cubic spline. Twelve studies involving 832,956 participants for total coffee consumption, 5 studies involving 717,151 participants for caffeinated coffee consumption and 6 studies involving 718,231 participants for decaffeinated coffee consumption were included in this meta-analysis. Compared with the lowest level of consumption, the pooled RRs were 0.80 (95 % CI 0.69-0.93, I (2) = 53.5 %), 0.85 (95 % CI 0.71-1.01, I (2) = 65.0 %) and 0.92 (95 % CI 0.81-1.05, I (2) = 0.0 %) for the consumption of total coffee, caffeinated coffee and decaffeinated coffee, respectively. In subgroup analysis by study design, the pooled RRs in cohort studies and case-control studies were 0.83 (95 % CI 0.72-0.97) and 0.74 (95 % CI 0.51-1.07) for total coffee consumption, respectively. Dose-response analysis suggested cutaneous melanoma risk decreased by 3 % [0.97 (0.93-1.00)] and 4 % [0.96 (0.92-1.01)] for 1 cup/day increment of total coffee and caffeinated coffee consumption, respectively. This meta-analysis suggests that coffee consumption may reduce the risk of cutaneous melanoma.


Identification of markers linked to genes for sprouting tolerance (independent of grain color) in hard white winter wheat (HWWW).
Hard red wheats can donate genes to hard white wheats for tolerance to preharvest sprouting, the effects are quantitative in nature, and may be tracked with previously described DNA markers. Pre-harvest sprouting (PHS) of wheat (Triticum aestivum L.) can negatively impact end-use quality and seed viability at planting. Due to preferences for white over red wheat in international markets, white wheat with PHS tolerance has become increasingly desired for worldwide wheat production. In general, however, red wheat is more tolerant of sprouting than white wheat. The main objective of this study was the identification of PHS tolerance conditioned by genes donated from hard red winter wheat, using markers applicable to the Great Plains hard white wheat gene pool. Three red wheat by white wheat populations, Niobrara/NW99L7068, NE98466/NW99L7068 and Jagalene/NW99L7068 were developed, and white-seeded progenies were analyzed for PHS tolerance and used to identify markers for the trait. In the three populations, marker loci with significant allelic effects were most commonly located on chromosomes of group 2, 3, 4 and 5, though additional markers were detected across the wheat genome. Chromosome 3A was the only chromosome with significant markers in all three populations. Markers were inconsistent across the three populations, and markers linked to tolerance-inducing loci were identified in both tolerant and susceptible parents. Additive effects of marker loci were common. In the present investigation, a wide range of PHS tolerance was observed, even though all lines were fixed for the recently reported positive TaPHS1 allele. PHS tolerance is controlled by additive major gene effects with minor gene effects where variations of minor gene effects were still unclear.


Delivery practices and associated factors among mothers seeking child welfare services in selected health facilities in Nyandarua South District, Kenya.
A measure of the proportion of deliveries assisted by skilled attendants is one of the indicators of progress towards achieving Millennium Development Goal (MDG) 5, which aims at improving maternal health. This study aimed at establishing delivery practices and associated factors among mothers seeking child welfare services at selected health facilities in Nyandarua South district, Kenya to determine whether mothers were receiving appropriate delivery care. A hospital-based cross-sectional survey among women who had recently delivered while in the study area was carried out between August and October 2009. Binary Logistic regression was used to identify factors that predicted mothers' delivery practice. Among the 409 mothers who participated in the study, 1170 deliveries were reported. Of all the deliveries reported, 51.8% were attended by unskilled birth attendants. Among the deliveries attended by unskilled birth attendants, 38.6% (452/1170) were by neighbors and/or relatives. Traditional Birth Attendants attended 1.5% (17/1170) of the deliveries while in 11.7% (137/1170) of the deliveries were self administered. Mothers who had unskilled birth attendance were more likely to have <3 years of education (Adjusted Odds ratio [AOR] 19.2, 95% confidence interval [CI] 1.7 - 212.8) and with more than three deliveries in a life time (AOR 3.8, 95% CI 2.3 - 6.4). Mothers with perceived similarity in delivery attendance among skilled and unskilled delivery attendants were associated with unsafe delivery practice (AOR 1.9, 95% CI 1.1 - 3.4). Mother's with lower knowledge score on safe delivery (%) were more likely to have unskilled delivery attendance (AOR 36.5, 95% CI 4.3 - 309.3). Among the mothers interviewed, utilization of skilled delivery attendance services was still low with a high number of deliveries being attended by unqualified lay persons. There is need to implement cost effective and sustainable measures to improve the quality of maternal health services with an aim of promoting safe delivery and hence reducing maternal mortality.


Comparison of noninvasive fluorescent and bioluminescent small animal optical imaging.
Optical imaging is a modality that is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. For this study, we used a green fluorescent protein (GFP)- and luciferase-expressing mouse tumor model to compare and contrast the quantitative and qualitative capabilities of a fluorescent reporter gene (GFP) and a bioluminescent reporter gene (luciferase). We describe the relationship between tumor volume, tumor mass, and bioluminescent/fluorescent intensity for both GFP and luciferase. Bioluminescent luciferase imaging was shown to be more sensitive than fluorescent GFP imaging. Luciferase-expressing tumors were detected as early as 1 day after tumor cell inoculation, whereas GFP-expressing tumors were not detected until 7 days later. Both bioluminescent and fluorescent intensity correlated significantly and linearly with tumor volume and tumor weight, as measured by caliper. Compared to bioluminescent imaging, fluorescent imaging does not require the injection of a substrate and may be appropriate for applications where sensitivity is not as critical. Knowing the relative strengths of each imaging modality will be important in guiding the decision to use fluorescence or bioluminescence.


Factors associated with the intent of firearm-related injuries in pediatric trauma patients.
To examine the characteristics of unintentional and assaultive firearm-related pediatric injuries treated in trauma centers. Comparative analysis of patients 14 years or younger who were admitted to the trauma centers because of unintentional firearm-related injuries (n = 292) vs assaultive firearm-related injuries (n = 457). Sixty-eight trauma centers or children's hospitals in the continental United States and Canada that reported data to the National Pediatric Trauma Registry from January 1, 1990, through December 31, 1994. Frequency distributions of firearm-related injuries in relation to intent and injury circumstances, odds ratios (ORs) on the intent of injury being assaultive, injury severity scales, and in-hospital fatality rates. The frequency of unintentional firearm-related injuries rose in the afternoons peaking between 4 and 5 PM; they predominantly occurred at home (89%). Assaultive firearm-related injuries peaked sharply between 8 and 9 PM and usually occurred on roads or in other public places (63%). About 3 times as many boys as girls were harmed in firearm-related injuries. Given a firearm-related injury resulting in admission to a trauma center, the adjusted OR of it being assaultive was 2.8 (95% confidence interval [CI], 1.6-4.6) if the victim was a girl, 4.9 (95% CI, 3.1-7.8) if the shooting occurred at night, 2.6 (95% CI, 1.6-4.2) if the shooting occurred on a weekday, and 21.1 (95% CI, 9.1-49.4) if the shooting occurred on a road. Injury patterns and severity were similar between patients with unintentional and assaultive injuries. Overall, 19% of the patients sustained head injuries, which contributed to 90% of the in-hospital deaths. Marked differences in injury circumstances exist between unintentional and assaultive firearm-related injuries among children. The late afternoon hours when many children have come home from school but their parents may still be working have the highest frequency of unintentional firearm-related injuries. The evening peak of assaultive injuries may be related to drug-related and gang-related violence. While it is important to reduce the access of firearms to children, school-based extracurricular and community-based social services should be considered in developing intervention programs.


Marijuana Use, Recent Marijuana Initiation, and Progression to Marijuana Use Disorder Among Young Male and Female Adolescents Aged 12-14 Living in US Households.
Marijuana initiation during adolescence, and early adolescence in particular, is associated with adverse health consequences. Our study used 2005-2014 data from the annual, cross-sectional National Survey on Drug Use and Health to study the prevalence and correlates of marijuana initiation, use, and marijuana use disorder (MUD; abuse or dependence) among 12- to 14-year olds living in civilian US households (n = 84 954). Examined correlates included age, sex, race/ethnicity, poverty status, metropolitan status, year of survey, depression, tobacco use, alcohol use, and fighting at school. Sex differences in the correlates of lifetime use and past year marijuana initiation were tested via interaction. Lifetime prevalence of marijuana use was 5.5%; 3.2% reported past year initiation. About 1 in 6 (16.8%) past year initiates progressed to MUD within 12 months of first use. Although men had higher prevalence of lifetime use than women, past year initiation did not differ by sex. On examining the sex*race/ethnicity interaction effects, findings determined that non-Hispanic black and Hispanic men had higher prevalence estimates of ever using marijuana and incidence of past year initiation as compared with non-Hispanic white men; these race/ethnicity differences were not found among women. Identifying correlates of initiation and progression to MUD among young adolescents is critical to improve prevention and treatment program targets.


Sun and aureole spectrometer for airborne measurements to derive aerosol optical properties.
We have designed an airborne spectrometer system for the simultaneous measurement of the direct Sun irradiance and aureole radiance. The instrument is based on diffraction grating spectrometers with linear image sensors. It is robust, lightweight, compact, and reliable, characteristics that are important for airborne applications. The multispectral radiation measurements are used to derive optical properties of tropospheric aerosols. We extract the altitude dependence of the aerosol volume scattering function and of the aerosol optical depth by using flight patterns with descents and ascents ranging from the surface level to the top of the boundary layer. The extinction coefficient and the product of single scattering albedo and phase function of separate layers can be derived from the airborne measurements.


Multimonth Prescription of Antiretroviral Therapy Among Children and Adolescents: Experiences From the Baylor International Pediatric AIDS Initiative in 6 African Countries.
To reach 90-90-90 targets, differentiated approaches to care are necessary. We describe the experience of delivering multimonth prescription (MMP) schedules of antiretroviral therapy (ART) to youth at centers of excellence in 6 African countries. We analyzed data from electronic medical records of patients aged 0-19 years started on ART. Patients were eligible to transition from monthly prescribing to MMP when clinically stable [improving CD4, viral load (VL) suppression, or minimal HIV-associated morbidity] and ART adherent (pill count 95%-105%). Patients were classified as transitioned to MMP after 3 consecutive visits at intervals of >56 days. We used survival analysis to describe death and lost to follow-up. We described adherence and acceptable immunologic response by CD4 using 6-month and VL suppression (<400 copies per milliliter) using 12-month intervals. Twenty-two thousand six hundred fifty-eight patients aged 0-19 years received ART and 14,932 (66%) transitioned to MMP between 2003 and 2015. Of these 2.6% were lost to follow-up and 2.0% died. Median duration of MMP was 3.9 (interquartile range: 2.2-5.9) years. There were significant differences in survival (P < 0.0001) between age groups, worst among those younger than 1 year and 15-19 years. The frequency of favorable clinical endpoints was high throughout the first 5 years of MMP, by year ranging from 87% to 94% acceptable immunologic response, 75% to 80% adherent, and 79% to 85% VL suppression. These analyses from 6 African countries demonstrate that youth on ART who transitioned to MMP overall maintained favorable outcomes in terms of death, retention, adherence, immunosuppression, and viral suppression. These results reassure that children and adolescents, who are clinically stable and ART adherent, can do well with reduced visit frequencies and extended ART refills.


Quantification of extinction risk: IUCN's system for classifying threatened species.
The International Union for Conservation of Nature (IUCN) Red List of Threatened Species was increasingly used during the 1980s to assess the conservation status of species for policy and planning purposes. This use stimulated the development of a new set of quantitative criteria for listing species in the categories of threat: critically endangered, endangered, and vulnerable. These criteria, which were intended to be applicable to all species except microorganisms, were part of a broader system for classifying threatened species and were fully implemented by IUCN in 2000. The system and the criteria have been widely used by conservation practitioners and scientists and now underpin one indicator being used to assess the Convention on Biological Diversity 2010 biodiversity target. We describe the process and the technical background to the IUCN Red List system. The criteria refer to fundamental biological processes underlying population decline and extinction. But given major differences between species, the threatening processes affecting them, and the paucity of knowledge relating to most species, the IUCN system had to be both broad and flexible to be applicable to the majority of described species. The system was designed to measure the symptoms of extinction risk, and uses 5 independent criteria relating to aspects of population loss and decline of range size. A species is assigned to a threat category if it meets the quantitative threshold for at least one criterion. The criteria and the accompanying rules and guidelines used by IUCN are intended to increase the consistency, transparency, and validity of its categorization system, but it necessitates some compromises that affect the applicability of the system and the species lists that result. In particular, choices were made over the assessment of uncertainty, poorly known species, depleted species, population decline, restricted ranges, and rarity; all of these affect the way red lists should be viewed and used. Processes related to priority setting and the development of national red lists need to take account of some assumptions in the formulation of the criteria.


Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.


Item- and task-level processes in the left inferior prefrontal cortex: positive and negative correlates of encoding.
Activity in the left inferior prefrontal cortex (LIPC) is often thought to reflect processes that support episodic encoding. Functional magnetic resonance imaging (fMRI) was used to test whether processes subserved by LIPC could be negatively related to subsequent memory performance. Specifically, the current experiment explicitly tested the hypothesis that LIPC processing would positively impact encoding when primarily focused towards specific target items (item-level processing), whereas it would negatively impact encoding when primarily focused on the retrieval and instantiation of current task instructions (task-level processing). Two methods were used to identify regions that were sensitive to the two types of processes: a block-level manipulation of encoding task that influenced subsequent memory, and a back-sort procedure. LIPC was sensitive to item- and task-level processing, but not in a way that always facilitates encoding. LIPC was more active for subsequently remembered words than subsequently forgotten words, but it was also more active in a task that emphasized task-level processing relative to a task that emphasized item-level processing, although this former condition led to poorer subsequent memory performance. This pattern indicates that processes subserved by LIPC are not always positively correlated with episodic encoding. Rather, LIPC processes can support both the controlled semantic processing of items and the controlled retrieval of relevant semantic task context. When devoted to the latter, the diversion of LIPC processes to the task level can have a negative consequence for item-level analysis and encoding.


Clinical practice guidelines for the noninvasive management of low back pain: A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.
We conducted a systematic review of guidelines on the management of low back pain (LBP) to assess their methodological quality and guide care. We synthesized guidelines on the management of LBP published from 2005 to 2014 following best evidence synthesis principles. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane, DARE, National Health Services Economic Evaluation Database, Health Technology Assessment Database, Index to Chiropractic Literature and grey literature. Independent reviewers critically appraised eligible guidelines using AGREE II criteria. We screened 2504 citations; 13 guidelines were eligible for critical appraisal, and 10 had a low risk of bias. According to high-quality guidelines: (1) all patients with acute or chronic LBP should receive education, reassurance and instruction on self-management options; (2) patients with acute LBP should be encouraged to return to activity and may benefit from paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), or spinal manipulation; (3) the management of chronic LBP may include exercise, paracetamol or NSAIDs, manual therapy, acupuncture, and multimodal rehabilitation (combined physical and psychological treatment); and (4) patients with lumbar disc herniation with radiculopathy may benefit from spinal manipulation. Ten guidelines were of high methodological quality, but updating and some methodological improvements are needed. Overall, most guidelines target nonspecific LBP and recommend education, staying active/exercise, manual therapy, and paracetamol or NSAIDs as first-line treatments. The recommendation to use paracetamol for acute LBP is challenged by recent evidence and needs to be revisited. Most high-quality guidelines recommend education, staying active/exercise, manual therapy and paracetamol/NSAIDs as first-line treatments for LBP. Recommendation of paracetamol for acute LBP is challenged by recent evidence and needs updating.


The course of depressive symptoms with decline in cognitive function - a longitudinal study of older adults receiving in-home care at baseline.
Depressive symptoms in old age are common, but the prevalence, persistence, and incidence of depressive symptoms in older adults with and without dementia receiving in-home care is less well studied, and descriptions of the relationship between severity of cognitive decline and depressive symptoms over time is, to our knowledge, lacking. The aim of the present study was to describe the prevalence, incidence and persistence of depressive symptoms over a 36-month follow-up period among older adults receiving in-home care at baseline, and to explore the association between cognitive function and the course of depressive symptoms over time. In all, 1001 older people (≥ 70 years) receiving in-home care were included in a longitudinal study with three assessments over 36 months. Depressive symptoms were assessed using the Cornell Scale for Depression in Dementia. Clinical Dementia Rating Scale, diagnosis of dementia and mild cognitive impairment, general medical health, personal and instrumental activities of daily living, neuropsychiatric symptoms and the use of psychotropic medication were evaluated during the three assessments. Baseline demographic characteristics and information on nursing home residency at follow-up were recorded. Linear mixed models were estimated. The baseline prevalence and cumulative incidence of single depressive symptoms were higher in those with dementia at baseline than in those without dementia. The persistence of depressive symptoms did not differ between those with or without dementia at baseline. The severity of cognitive impairment and mean depressive symptom score assessed simultaneously were positively associated, but the strength of the association changed over time and was not significant at the last assessment. Furthermore, being younger, female, in very poor physical health, with neuropsychiatric symptoms and not becoming a nursing home resident were associated with more depressive symptoms when assessed simultaneously. The baseline prevalence and cumulative incidence of depressive symptoms in those with and without dementia at baseline, as well as the relationship we found between the degree of cognitive decline and depressive symptoms over time show that depression and dementia are interconnected. Nurses and clinicians should pay attention to cognitive status when observing or evaluating depression among older adults receiving in-home care.


Enhanced noble gas adsorption in Ag@MOF-74Ni.
Various amounts of Ag nanoparticles were successfully deposited in porous MOF-74Ni (or Ni/DOBDC) by an auto-reduction method. An optimized silver-loaded MOF-74Ni was shown to have an improved Xe adsorption capacity (15% more) at STP compared to the MOF without silver nanoparticles. The silver-loaded sample also has a higher Xe/Kr selectivity. These results are explained by the stronger interactions between polarizable Xe molecules and the well-dispersed Ag nanoparticles.


Frontal brain asymmetry and reward responsiveness: a source-localization study.
The influence of approach and avoidance tendencies on affect, reasoning, and behavior has attracted substantial interest from researchers across various areas of psychology. Currently, frontal electroencephalographic (EEG) asymmetry in favor of left prefrontal regions is assumed to reflect the propensity to respond with approach-related tendencies. To test this hypothesis, we recorded resting EEG in 18 subjects, who separately performed a verbal memory task under three incentive conditions (neutral, reward, and punishment). Using a source-localization technique, we found that higher task-independent alpha2 (10.5-12 Hz) activity within left dorsolateral prefrontal and medial orbitofrontal regions was associated with stronger bias to respond to reward-related cues. Left prefrontal resting activity accounted for 54.8% of the variance in reward bias. These findings not only confirm that frontal EEG asymmetry modulates the propensity to engage in appetitively motivated behavior, but also provide anatomical details about the underlying brain systems.


Autophagy is impaired in cardiac ischemia-reperfusion injury.
Accumulating evidence attests to a prosurvival role for autophagy under stress, by facilitating removal of damaged proteins and organelles and recycling basic building blocks, which can be utilized for energy generation and targeted macromolecular synthesis to shore up cellular defenses. These observations are difficult to reconcile with the dichotomous prosurvival and death-inducing roles ascribed to macroautophagy in cardiac ischemia and reperfusion injury, respectively. A careful reexamination of 'flux' through the macroautophagy pathway reveals that autophagosome clearance is markedly impaired with reperfusion (reoxygenation) in cardiomyocytes following an ischemic (hypoxic) insult, resulting from reactive oxygen species (ROS)-mediated decline in LAMP2 and increase in BECN1 abundance. This results in impaired autophagy that is 'ineffective' in protecting against cell death with ischemia-reperfusion injury. Restoration of autophagosome clearance and by inference, 'adequate' autophagy, attenuates reoxygenation-induced cell death.


Modulation of gain-of-function α6*-nicotinic acetylcholine receptor by β3 subunits.
We previously have shown that β3 subunits either eliminate (e.g. for all-human (h) or all-mouse (m) α6β4β3-nAChR) or potentiate (e.g. for hybrid mα6hβ4hβ3- or mα6mβ4hβ3-nAChR containing subunits from different species) function of α6*-nAChR expressed in Xenopus oocytes, and that nAChR hα6 subunit residues Asn-143 and Met-145 in N-terminal domain loop E are important for dominant-negative effects of nAChR hβ3 subunits on hα6*-nAChR function. Here, we tested the hypothesis that these effects of β3 subunits would be preserved even if nAChR α6 subunits harbored gain-of-function, leucine- or valine-to-serine mutations at 9' or 13' positions (L9'S or V13'S) in their second transmembrane domains, yielding receptors with heightened functional activity and more amenable to assessment of effects of β3 subunit incorporation. However, coexpression with β3 subunits potentiates rather than suppresses function of all-human, all-mouse, or hybrid α6((L9'S or V13'S))β4*- or α6(N143D+M145V)(L9'S)β2*-nAChR. This contrasts with the lack of consistent function when α6((L9'S or V13'S)) and β2 subunits are expressed alone or in the presence of wild-type β3 subunits. These results provide evidence that gain-of-function hα6hβ2*-nAChR (i.e. hα6(N143D+M145V)(L9'S)hβ2hβ3 nAChR) could be produced in vitro. These studies also indicate that nAChR β3 subunits can be assembly partners in functional α6*-nAChR and that 9' or 13' mutations in the nAChR α6 subunit second transmembrane domain can act as gain-of-function and/or reporter mutations. Moreover, our findings suggest that β3 subunit coexpression promotes function of α6*-nAChR.


Mechanistic insights into replication termination as revealed by investigations of the Reb1-Ter3 complex of Schizosaccharomyces pombe.
Relatively little is known about the interaction of eukaryotic replication terminator proteins with the cognate termini and the replication termination mechanism. Here, we report a biochemical analysis of the interaction of the Reb1 terminator protein of Schizosaccharomyces pombe, which binds to the Ter3 site present in the nontranscribed spacers of ribosomal DNA, located in chromosome III. We show that Reb1 is a dimeric protein and that the N-terminal dimerization domain of the protein is dispensable for replication termination. Unlike its mammalian counterpart Ttf1, Reb1 did not need an accessory protein to bind to Ter3. The two myb/SANT domains and an adjacent, N-terminal 154-amino-acid-long segment (called the myb-associated domain) were both necessary and sufficient for optimal DNA binding in vitro and fork arrest in vivo. The protein and its binding site Ter3 were unable to arrest forks initiated in vivo from ars of Saccharomyces cerevisiae in the cell milieu of the latter despite the facts that the protein retained the proper affinity of binding, was located in vivo at the Ter site, and apparently was not displaced by the "sweepase" Rrm3. These observations suggest that replication fork arrest is not an intrinsic property of the Reb1-Ter3 complex.


Challenges and opportunities for alkane functionalisation using molecular catalysts.
The conversion of vast low-value saturated hydrocarbons into valuable chemicals is of great interest. Thanks to the progression of organometallic and coordination chemistry, transition metal catalysed C sp3-H bond functionalisation has now become a powerful tool for alkane transformations. Specifically, methods for alkane functionalisation include radical initiated C-H functionalisation, carbene/nitrene insertion, and transition metal catalysed C-H bond activation. This perspective provides a systematic and concise overview of each protocol, highlighting the factors that govern regioselectivity in these reactions. The challenges of the existing catalytic tactics and future directions for catalyst development in this field will be presented.


Role of botulinum toxin-A in management of refractory idiopathic detrusor overactive bladder: Single center experience.
Overactive bladder (OAB) is a bothersome condition affecting the quality of life, financial constraint on the individual, and community. Anticholinergic drugs cannot be used for long term due to adverse side effects. Botulinum toxin has recently shown promising and encouraging result in management of OAB. Aim was to study the safety, efficacy, tolerability, and duration of effect of 200 units of botulinum toxin in refractory idiopathic detrusor overactivity. Thirty-nine female patients (average age of 52 years) clinically and urodynamically diagnosed as idiopathic OAB were injected 200 units of botulinum toxin-A mixed with 20 ml of normal saline, intradetrusally at the rate of 1 mL at each site for 20 such sites sparing the trigone and ureteric orifices. Follow up at 3rd, 6th, 9th, and 12th month with clinical and urodynamical questionnaire was done. There were 4 dropouts and 35 patients were evaluated, of which 30 patients (85.7%) showed improvement in clinical features like frequency, urgency, nocturia, and incontinence within 1 week of injection, which lasted for mean period of 7 months (varying from 6 to 9 months). Volume at first desire to void improved from median baseline of 104-204 ml and maximum cystometric capacity of bladder increased from mean baseline value of 205-330 ml. The detrusor pressure decreased by 49% from the baseline and postresidual urine volume increased by 30% of maximum cystometric capacity of bladder. There was no adverse effect on our patient. Intradetrusor injection of Botox-A in management of refractory overactive idiopathic bladder is not only safe and well tolerated, but also very effective with practically no side effects.


Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons.
Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing cholinergic interneurons with simultaneous detection of dopamine release at carbon-fiber microelectrodes in striatal slices. We reveal that activation of cholinergic interneurons by light flashes that cause only single action potentials in neurons from a small population triggers dopamine release via activation of nicotinic receptors on dopamine axons. This event overrides ascending activity from dopamine neurons and, furthermore, is reproduced by activating ChR2-expressing thalamostriatal inputs, which synchronize cholinergic interneurons in vivo. These findings indicate that synchronized activity in cholinergic interneurons directly generates striatal dopamine signals whose functions will extend beyond those encoded by dopamine neuron activity.


The DNA binding and accumulation of p53 from breast cancer cell lines and the link with serine 15 phosphorylation.
Stress treatment generally causes the post-translational modification and accumulation of the p53 protein, although the role of these aspects has not been always understood in relation to this protein's tumor suppressor activity. We analyzed these attributes of p53 in eight different breast cancer cell lines, with either wild-type or mutant p53 protein, in response to oxidative stress. We found that the wild-type p53 protein from MCF-7 and ZR-75-1 cells binds with different affinity to 12 gene sequences covering several pathways regulated by p53. Treatment of MCF-7 cells with H2O2 caused an increase in this binding affinity while this same treatment of ZR-75-1 cells caused the p53 protein to lose binding affinity to several genes. The mutant p53 proteins from all cell lines had minimal to weak binding to these sequences even after treatment with H2O2. The p53 protein from the ZR-75-1 cells and three cell lines with mutant p53 showed serine 15 phosphorylated protein, but we found no correlation between that modification and the levels or localization of this protein although DNA binding affinity of wild-type protein might be affected by this modification. From this and other work, it appears that the mutation status of the TP53 gene alone cannot predict the activity of this tumor suppressor since cell lines with the same genetic information do not show the same properties of this protein.


HyperSPASM NMR: a new approach to single-shot 2D correlations on DNP-enhanced samples.
Dissolution DNP experiments are limited to a single or at most a few scans, before the non-Boltzmann magnetization has been consumed. This makes it impractical to record 2D NMR data by conventional, t(1)-incremented schemes. Here a new approach termed HyperSPASM to establish 2D heteronuclear correlations in a single scan is reported, aimed at dealing with this kind of challenge. The HyperSPASM experiment relies on imposing an amplitude-modulation of the data by a single Δt(1) indirect-domain evolution time, and subsequently monitoring the imparted encoding on separate echo and anti-echo pathway signals within a single continuous acquisition. This is implemented via the use of alternating, switching, coherence selection gradients. As a result of these manipulations the phase imparted by a heteronucleus over its indirect domain evolution can be accurately extracted, and 2D data unambiguously reconstructed with a single-shot excitation. The nature of this sequence makes the resulting experiment particularly well suited for collecting indirectly-detected HSQC data on hyperpolarized samples. The potential of the ensuing HyperSPASM method is exemplified with natural-abundance hyperpolarized correlations on model systems.


Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.
The EACVI/ASE/Industry Task Force to standardize deformation imaging prepared this consensus document to standardize definitions and techniques for using two-dimensional (2D) speckle tracking echocardiography (STE) to assess left atrial, right ventricular, and right atrial myocardial deformation. This document is intended for both the technical engineering community and the clinical community at large to provide guidance on selecting the functional parameters to measure and how to measure them using 2D STE.This document aims to represent a significant step forward in the collaboration between the scientific societies and the industry since technical specifications of the software packages designed to post-process echocardiographic datasets have been agreed and shared before their actual development. Hopefully, this will lead to more clinically oriented software packages which will be better tailored to clinical needs and will allow industry to save time and resources in their development.


A novel approach to the diagnosis of stress-induced cardiomyopathy.
Stress-induced cardiomyopathy is becoming a more commonly recognized diagnosis, accounting for 2% to 3% of patients presenting with signs and symptoms of acute anterior myocardial infarction. We present the case of a 68-year-old man with dyspnea 9 days after an unrelated operation. After hospital admission, he complained of chest pain, and an electrocardiogram demonstrated ST-segment elevation in the anterolateral and inferior leads, ST-segment depression in lead aVR, and an absence of ST-segment changes in lead V(1). Cardiac biomarker levels were elevated. Transthoracic echocardiography demonstrated a left ventricular ejection fraction of 30% to 40%, basilar hyperactivity, apical dyskinesia, and distal inferior and anterior akinesia. Cardiac catheterization did not reveal any culprit obstructive lesion. He received a diagnosis of stress-induced cardiomyopathy and was treated according to established recommendations for systolic heart failure. His cardiac biomarkers returned to normal, and a repeated transthoracic echocardiogram 3 days later revealed nearly complete resolution of myocardial wall-motion abnormalities.


Ginseng treatment improves psychomotor performance at rest and during graded exercise in young athletes.
This study was designed to determine the effect of ginseng treatment on multiple choice reaction time (RT) during exercise. Fifteen soccer players (age 19.07 +/- 0.62 yrs) were placed in a double-blind manner into one of two groups: ginseng (n = 7), receiving 350 mg of ginseng daily for 6 weeks, or placebo (n = 8), receiving a placebo daily for 6 weeks. Before and after the treatment all the subjects performed an incremental bicycle ergometer exercise with intensity increasing 50 W every 3 min until volitional exhaustion. RT was measured before exercise, and then in the last 2 min of each exercise load. Maximal oxygen uptake (VO2max) and lactate threshold (LAT) were also determined from the exercise test. Ginseng treatment was found to shorten RT at rest and during exercise, shifting the exercise load associated with the shortest RT toward higher exercise loads. Neither ginseng nor placebo influenced VO2 max and LAT. In conclusion, ginseng extract does improve psychomotor performance during exercise without affecting exercise capacity.


Adjuvant TNF-α therapy to electrochemotherapy with intravenous cisplatin in murine sarcoma exerts synergistic antitumor effectiveness.
Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor α (TNF-α) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. In vivo study was designed to evaluate the effect of TNF-α applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-α on electrochemotherapy with different cisplatin doses. A synergistic interaction between TNF-α and electrochemotherapy was observed. Administration of TNF-α before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-α administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-α induced blood vessel damage and increased tumour necrosis after combination of TNF-α and electrochemotherapy, indicating an anti-vascular action of TNF-α. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Adjuvant intratumoural TNF-α therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.


2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile as novel inhibitor of receptor tyrosine kinase and PI3K/AKT/mTOR signaling pathway in glioblastoma.
Nerve growth factor receptor (NGFR), a member of kinase protein, is emerging as an important target for Glioblastoma (GBM) treatment. Overexpression of NGFR is observed in many metastatic cancers including GBM, promoting tumor migration and invasion. Hydrazones have been reported to effectively interact with receptor tyrosine kinases (RTKs). We report herein the synthesis of 23 arylhydrazones of active methylene compounds (AHAMCs) compounds and their anti-proliferative activity against GBM cell lines, LN229 and U87. Compound R234, 2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile, was identified as the most active anti-neoplastic compound, with the IC50 value ranging 87 μM - 107 μM. Molecular docking simulations of the synthesized compounds into the active site of tyrosine receptor kinase A (TrkA), demonstrated a strong binding affinity with R234 and concurs well with the obtained biological results. R234 was found to be a negative regulator of PI3K/Akt/mTOR pathway and an enhancer of p53 expression. In addition, R234 treated GBM cells exhibited the downregulation of cyclins, cyclin-dependent kinases and other key molecules involved in cell cycle such as CCNE, E2F, CCND, CDK6, indicating that R234 induces cell cycle arrest at G1/S. R234 also exerted its apoptotic effects independent of caspase3/7 activity, in both cell lines. In U87 cells, R234 induced oxidative effects whereas LN229 cells annulled oxidative stress. The study thus concludes that R234, being a negative modulator of RTKs and cell cycle inhibitor, may represent a novel class of anti-GBM drugs.


The loop B domain is physically separable from the loop A domain in the hairpin ribozyme.
In order to understand the catalysis mechanism of the hairpin ribozyme, mutant ribozymes were constructed. The distance between the loop A domain and the loop B domain was extended by inserting various lengths of nucleotide linkers at the hinge region in cis mutants, or the domains were separated physically in a trans mutant. All the mutant ribozymes, including the trans mutant, could cleave substrate RNA at the predicted site. A cis mutant with a single nucleotide insertion exhibited cleavage activity about twice as high as that of the wild-type (wt) ribozyme. The insertion of 2-5 nucleotides (nt) gradually reduced the activity to the level of the wt ribozyme. Insertion of a longer linker, up to 11 nt, resulted in the reduction of activity to one half of that of the wt ribozyme. The ribozyme with a single nucleotide insertion at the hinge region seems to form a more suitable conformation for catalysis by three-dimensional fold-back of the loop B to loop A containing the cleavage site. The trans mutant, in which the A and B domains were physically separated, maintained a significant level of activity, suggesting that both domains are necessary for catalysis, but separable. These results demonstrate that interaction between the A and B domains results in catalysis.


Time domain DNP with the NOVEL sequence.
We present results of a pulsed dynamic nuclear polarization (DNP) study at 0.35 T (9.7 GHz/14.7 MHz for electron/(1)H Larmor frequency) using a lab frame-rotating frame cross polarization experiment that employs electron spin locking fields that match the (1)H nuclear Larmor frequency, the so called NOVEL (nuclear orientation via electron spin locking) condition. We apply the method to a series of DNP samples including a single crystal of diphenyl nitroxide (DPNO) doped benzophenone (BzP), 1,3-bisdiphenylene-2-phenylallyl (BDPA) doped polystyrene (PS), and sulfonated-BDPA (SA-BDPA) doped glycerol/water glassy matrices. The optimal Hartman-Hahn matching condition is achieved when the nutation frequency of the electron matches the Larmor frequency of the proton, ω(1S) = ω(0I), together with possible higher order matching conditions at lower efficiencies. The magnetization transfer from electron to protons occurs on the time scale of ∼100 ns, consistent with the electron-proton couplings on the order of 1-10 MHz in these samples. In a fully protonated single crystal DPNO/BzP, at 270 K, we obtained a maximum signal enhancement of ε = 165 and the corresponding gain in sensitivity of ε(T1/T(B))(1/2)=230 due to the reduction in the buildup time under DNP. In a sample of partially deuterated PS doped with BDPA, we obtained an enhancement of 323 which is a factor of ∼3.2 higher compared to the protonated version of the same sample and accounts for 49% of the theoretical limit. For the SA-BDPA doped glycerol/water glassy matrix at 80 K, the sample condition used in most applications of DNP in nuclear magnetic resonance, we also observed a significant enhancement. Our findings demonstrate that pulsed DNP via the NOVEL sequence is highly efficient and can potentially surpass continuous wave DNP mechanisms such as the solid effect and cross effect which scale unfavorably with increasing magnetic field. Furthermore, pulsed DNP is also a promising avenue for DNP at high temperature.


Patterns of seatbelt use in different socioeconomic communities in the Cape Town Metropole, South Africa.
BACKGROUND; Road traffic injuries are a leading cause of death and may be related to social inequality. To establish whether patterns of seatbelt use vary between different socioeconomic communities in the Cape Town Metropole, South Africa. Vehicles and their occupants at 7 high-volume crossings (3 in high-income areas) were placed under surveillance for 2 hours each during November 2010. All occupants were eligible for inclusion except occupants of non-motorised vehicles, two-wheel motorised vehicles, buses, taxis, heavy goods vehicles and emergency vehicles. Child seatbelt use was recorded only for children who appeared older than 3 years. A total of 4 651 vehicles with 6 848 occupants were surveyed. Rates of seatbelt use were 45.1% (n=3 090) for all occupants, 54.0% (n=2 513) for drivers, 33.1% (n=521) for front-seat passengers (adults 33.2%, n=452; children 32.7%, n=69) and 9.0% (n=56) for rear-seat passengers (adults 4.0%, n=13; children 14.4%, n=43). Occupants from high-income areas were more likely to wear seatbelts (odds ratio (OR) 4.35; 95% confidence interval (CI) 3.89 - 4.88). Use of child restraints was poor overall (22.3%, n=114), but also varied according to income areas (high income 40.9%, n=99; low income 0.03%, n=6; OR 26.77; 95% CI 11.44 - 62.63). The impact of road traffic injuries is significant, but can be decreased by using appropriate restraining devices. Seatbelt use in South Africa, although compulsory, is neither strictly adhered to nor enforced. Their use is proportionally lower in lower-income areas. Specific interventions are required to target these communities directly.


The Impact of Carboxylesterases in Drug Metabolism and Pharmacokinetics.
Carboxylesterases (CES) play a critical role in catalyzing hydrolysis of esters, amides, carbamates and thioesters, as well as bioconverting prodrugs and soft drugs. The unique tissue distribution of CES enzymes provides great opportunities to design prodrugs or soft drugs for tissue targeting. Marked species differences in CES tissue distribution and catalytic activity are particularly challenging in human translation. Review and summarization of CES fundamentals and applications in drug discovery and development. Human CES1 is one of the most highly expressed drug metabolizing enzymes in the liver, while human intestine only expresses CES2. CES enzymes have moderate to high inter-individual variability and exhibit low to no expression in the fetus, but increase substantially during the first few months of life. The CES genes are highly polymorphic and some CES genetic variants show significant influence on metabolism and clinical outcome of certain drugs. Monkeys appear to be more predictive of human pharmacokinetics for CES substrates than other species. Low risk of clinical drug-drug interaction is anticipated for CES, although they should not be overlooked, particularly interaction with alcohols. CES enzymes are moderately inducible through a number of transcription factors and can be repressed by inflammatory cytokines. Although significant advances have been made in our understanding of CESs, in vitro - in vivo extrapolation of clearance is still in its infancy and further exploration is needed. In vitro and in vivo tools are continuously being developed to characterize CES substrates and inhibitors.


Outcomes of Descemet Stripping Endothelial Keratoplasty in Eyes With Pars Plana Versus Anterior Chamber Glaucoma Drainage Devices.
To compare visual outcomes and complications of Descemet stripping endothelial keratoplasty (DSEK) in eyes with anterior chamber (AC) versus pars plana (PP) glaucoma drainage devices (GDDs). A retrospective chart review was conducted of 85 eyes that underwent DSEK and had previous or concurrent AC (37 eyes) or PP (48 eyes) GDD implantation. Outcome measures examined included visual acuity, donor dislocation rate, intraocular pressure, and secondary graft failure (SGF). The mean logarithm of the minimum angle of resolution vision improved from 1.50 (SD = 0.64) to 0.88 (SD = 0.71) in the AC group and from 1.37 (SD = 0.59) to 1.20 (SD = 0.76) in the PP group, with no significant group difference. Intraocular pressure did not differ between the groups preoperatively but was higher in the AC group compared with the PP group postoperatively [mean (SD) 14.5 (6.28) versus 11.5 (5.54) mm Hg, P = 0.03]. Graft dislocation occurred in 35.1% and 29.2% of eyes in the AC and PP groups, respectively. SGF occurred in 18.9% and 41.7% with median time 17.1 (interquartile range [IQR] 4.6-32.1) and 27.9 (IQR 15.1-34.7) months to development in the AC and PP groups, respectively. Multivariable logistic and Cox proportional hazards regression models found no statistically significant factors (tube location, age, sex, concurrent tube revision, new tube insertion) associated with either donor dislocation or SGF. There was no reduction in donor dislocation or SGF in eyes with PP compared with AC GDD, despite the decreased proximity of the shunt from the endothelial graft. Overall, GDD has a significantly adverse effect on long-term graft survival and close follow-up is warranted.


Bis(selenobenzoato)dibutyltin(iv) as a single source precursor for the synthesis of SnSe nanosheets and their photo-electrochemical study for water splitting.
A new organo-tin complex has been synthesized and used as a single source precursor for the synthesis of SnSe nanosheets by the hot injection method and thin films by the aerosol assisted chemical vapor deposition (AACVD) method. The films were deposited on glass substrates at three different temperatures. The textural quality and preferential growth were found to be significantly altered by changes in the deposition temperature. Oleylamine capped nanosheets and the as-deposited thin films by AACVD were characterized by powder X-ray diffraction (p-XRD) and microscopic techniques. The thin films were also studied by Raman spectroscopy. The stoichiometry is marginally affected by temperature, and all films were slightly selenium deficient. The synthesized material was also evaluated for the photoelectrochemical (PEC) splitting of water. The PEC study revealed the bifunctional nature of the material, which can be applied for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), by switching the applied potential.


Crime Scene Reconstruction Using a Fully Geomatic Approach.
This paper is focused on two main topics: crime scene reconstruction, based on a geomatic approach, and crime scene analysis, through GIS based procedures. According to the experience of the authors in performing forensic analysis for real cases, the aforesaid topics will be examined with the specific goal of verifying the relationship of human walk paths at a crime scene with blood patterns on the floor. In order to perform such analyses, the availability of pictures taken by first aiders is mandatory, since they provide information about the crime scene before items are moved or interfered with. Generally, those pictures are affected by large geometric distortions, thus - after a brief description of the geomatic techniques suitable for the acquisition of reference data (total station surveying, photogrammetry and laser scanning) - it will be shown the developed methodology, based on photogrammetric algorithms, aimed at calibrating, georeferencing and mosaicking the available images acquired on the scene. The crime scene analysis is based on a collection of GIS functionalities for simulating human walk movements and creating a statistically significant sample. The developed GIS software component will be described in detail, showing how the analysis of this statistical sample of simulated human walks allows to rigorously define the probability of performing a certain walk path without touching the bloodstains on the floor.


The utility of the PAI and the MMPI-2 for discriminating PTSD, depression, and social phobia in trauma-exposed college students.
This study investigated the Minnesota Multiphasic Personality Inventory-Revised (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) and the Personality Assessment Inventory (PAI; Morey, 1991) with regard to each instrument's utility for discriminating post-traumatic stress disorder (PTSD) from depression and social phobia in a sample of college students with mixed civilian trauma exposure. Participants were 90 trauma-exposed undergraduates (16 male, 74 female) classified into one of four groups: PTSD, depressive disorders, social phobia, and well-adjusted. For both the PAI and the MMPI-2, profile analysis revealed that the groups differed in the elevation and shape of their profiles. The PAI Traumatic Stress subscale demonstrated good discriminant validity.