Recruitment of anterior dorsolateral prefrontal cortex in human reasoning: a parametric study of relational complexity.
Reasoning and problem solving depend on the ability to represent and integrate complex relationships among stimuli. For example, deciding whether an animal is dangerous requires integrating information about the type of animal, its size, its distance from oneself, and one's proximity to shelter. Relational complexity increases with the number of such interdependent elements that must be simultaneously considered to solve a problem. We used functional magnetic resonance imaging to identify brain regions that respond selectively in processing high levels of relational complexity. Performance on nonverbal reasoning problems in which relational complexity was varied parametrically was compared with performance on control problems in which relational complexity was held constant while difficulty was manipulated by adding distractor forms to the problems. Increasing complexity and adding distractors both led to increased activation in parietal and in dorsolateral prefrontal cortex, with high levels of relational complexity selectively activating anterior left prefrontal cortex. Our data provide evidence that brain regions specific to integrating complex relations among stimuli are distinct from those involved in coping with general task difficulty and with working-memory demands.


Could the organ shortage ever be met?
The organ shortage is commonly presented as having a clear solution, increase the number of organs donated and the problem will be solved. In the light of the Northern Ireland Assembly's consultation on moving to an opt-out organ donor register this article focuses on the social factors and complexities which impact strongly on both the supply of, and demand for, transplantable organs. Judging by the experience of other countries presumed consent systems may or may not increase donations but have not met demand. Donation rates have risen considerably in all parts of the UK recently but there is also an increasing demand for organs. Looking at international donation rates and attitudes, future demand for organs and education on donation, the question is whether the organ shortage could ever be met. The increase in longevity, in rates of diabetes and obesity and in alcohol related liver disease all contribute both to increased demand for transplants, and re-transplants, and a reduction in the number of usable organs. It is unlikely that demand could ever be met, since, if supply was unlimited, the focus would move to financial resources and competing demands on the health care budget in a publicly funded health system. These factors point to the need to focus on ways of reducing, or at least stabilizing, demand where lifestyle factors contribute to the underlying disease.


How the all fruits salad creates sweeter futures in rural and remote mental health.
This paper outlines evidence of efficacious outcomes from mixing people living with diverse mental health challenges and/or intellectual disability. The intention was to show how mixing up people who are differently challenged can be efficacious in (re)habilitation terms. Two separate experiences of sharing personal narratives were involved, along with creative expressions in music, art and filming, combined with group gatherings providing discerning feedback for each other on members' day-to-day progress. After 12 months of 'open urban tribe' gatherings in Sydney, where participants formed a community of belonging, the model was adapted for use in Alice Springs. The original group developed a cycle of interactive ritual rhythms, and these became a special feature of their self-help, peer support approach. The Sydney project modelled community-based rehabilitation, and that process then informed the processes initiated in a rural, remote location. Regular whole tribe gatherings 'in the circle' combined with mentoring 'aunties and uncles'. By sharing stories and giving personal feedback on their progress, participants developed skills and confidence in self expression. Relating to each other and the group, and sharing creative expressions (group craft activities, dancing, small group performing) added depth to the experience of participants. Stories and celebrations were filmed, along with meetings to discuss progress and reflect on how to improve our process of sharing together. Ways for individuals to work on improving their life experiences were shared across the group, which generated a combination of forms of inquiry: supportive, collaborative and appreciative. These were combined with reflexive qualitative ethnographic recording by the researcher, to report and reflect on the whole process. The original 12 month open urban tribe formation (May 2004-June 2005) in Sydney led to regular gatherings where participants sought to come together and celebrate their being with each other until 2007. From that model further work was undertaken in Alice Springs in early 2008, applying a smaller version of this approach to a new community group. The narrative testimony and witnessing in the first group formed one element of what participants called 'the magic', which they commented on throughout their time together. It was their way of just being together (what this author calls their 'metaphorical energetic presence' alongside each other) that carried the power of this tribe's interactions. Mirroring and feeding back messages to each other that they belonged, that they had an identity, role and purpose together, was a key influence on wellness. That they were seen and loved by all participants was a vital element in the dynamic. These combined to create an effect dubbed 'Working the Business of Life' (WTBOL), a group sharing process providing practical feedback on how to maintain balance in life. By giving everyone a sense of being nurtured in their day-to-day lives, WTBOL showed that people of mixed consciousness can assist each other's healing, growth and development. The value in mixing people of different challenges was that it created a rich field of exchange of their beingness, and mutual appreciation and support. Each had compassion for the other's challenge, and this helped their own process of growing beyond their own challenges. The process has now been successfully applied in Peer Support Training Workshops for Consumers and Carers (November 2008 in Alice Springs). Arising from this work, the All Fruits Theory (AFT) argues that mixing people of diverse consciousness, in contexts of trust and safety with each other, can lead to enriching personal acknowledgement and a sense of belonging. By sharing stories, joining celebratory activities, it is possible to generate interactive rhythmical ritual cycles of companionship, celebration, communion and contemplation. The project thus stimulated purposeful motivation and intention to engage in new activities. Individual and group social and emotional wellbeing were enhanced by participating. The author argues that these results show that, just as biodiversity is essential for ecological sustainability, 'onto-diversity' (i.e. valuing diverse ways of being and knowing) is what is needed in rehabilitation settings. When applied across cultures, ethnicity, gender, class and capability differences, these wiser ways of knowing can lead to more sustainable ways of being (i.e. what this author calls 'onto-diversity for suss-tainability', playing on the modern slang term for 'sussing things out'--meaning gaining better understanding of what's really going on).


Intranasal oxytocin in the treatment of autism spectrum disorders: A multilevel meta-analysis.
Intranasal oxytocin has been shown to promote social functioning and has recently been applied as a treatment for autism spectrum disorders (ASD). The current meta-analysis aims to assess the crucial question of oxytocin's efficacy in the treatment of ASD. We performed a systematic literature search, including randomized, single- or double-blind/open-label and placebo-controlled clinical trials as well as single-arm, non-randomized and uncontrolled studies investigating exogenous oxytocin effect on ASD. A total of 28 studies (N = 726 ASD patients) met our predefined inclusion criteria. We used a multilevel meta-analytic model and found that oxytocin had beneficial effects on social functioning, but did not find strong evidence for symptoms improvement in the non-social domain. Our findings suggest that oxytocin administration can be regarded as an effective treatment for some core aspects of ASD, especially in the domain of social functioning, highlighting the promise of using oxytocin as a new-generation therapeutic to address core social impairments in ASD.


An open-label trial of St. John's Wort (Hypericum perforatum) in obsessive-compulsive disorder.
Recent interest in and evidence for the efficacy of St. John's wort (Hypericum perforatum) for the treatment of mild-to-moderate depression has led to speculation about its efficacy in other disorders. Hypericum's mechanism of action is postulated to be via inhibition of the synaptosomal uptake of serotonin. As such, there is a suggestion that Hypericum may be effective for obsessive-compulsive disorder (OCD). Twelve subjects were evaluated with a primary DSM-IV diagnosis of OCD of at least 12 months' duration. Treatment lasted for 12 weeks, with a fixed dose of 450 mg of 0.3% hypericin (a psychoactive compound in Hypericum) twice daily (extended-release formulation). Weekly evaluations were conducted with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Patient Global Impressions of Improvement Scale, and the Clinical Global Impressions of Improvement scale (CGI) and monthly evaluation with the Hamilton Rating Scale for Depression. A significant change from baseline to endpoint was found, with a mean Y-BOCS change of 7.4 points (p = .001). Significant change occurred at 1 week (p = .020) and continued to increase throughout the trial. At endpoint, 5 (42%) of 12 were rated "much" or "very much improved" on the clinician-rated CGI, 6 (50%) were "minimally improved," and 1 (8%) had "no change." The most common side effects reported were diarrhea (N = 3) and restless sleep (N = 2). Significant improvement was found with Hypericum, with a drop-in Y-BOCS score similar to that found in clinical trials. The fact that a significant change was found as early as 1 week into treatment suggests a possible initial placebo response, although improvement grew larger over time. Results warrant a placebo-controlled study of Hypericum in OCD.


Modulations in androgen and estrogen mediating genes and testicular response in male goldfish exposed to bisphenol A.
Adverse effects of bisphenol A (BPA) on reproductive physiology were studied in male goldfish (Carassius auratus) exposed to nominal environmentally relevant concentrations (0.2 and 20 µg/L) for up to 90 d. Transcriptions of various reproductive genes were measured in brain, liver, and testis to investigate the BPA modes of action. Volume, density, total number, motility, and velocity of sperm were measured to assess testicular function. At 0.2 µg/L, BPA reduced steroidogenetic acute regulatory protein and increased estrogen receptors (ERs) messenger RNA (mRNA) transcript (ERβ1 in liver and ERβ2 in testis) after 90 d. At 20 µg/L, BPA increased mRNA transcript of androgen receptor in testis, brain- and testis-specific aromatase, and vitellogenin in liver after 90, 30, 60, and 60 d, respectively. Transcripts of ERs mRNA were increased after 30 to 60 d at 20 µg/L BPA; increase in ERβ1 mRNA was observed in testis after 7 d. Total number, volume, and motility of sperm were decreased in males exposed to 0.2 and 20 µg/L BPA, whereas sperm density and velocity were only reduced at 20 µg/L BPA. The results support the hypothesis that BPA may exert both anti-androgenic and estrogenic effects, depending on concentration, leading to diminished sperm quality. The findings provide a framework for better understanding of the mechanisms mediating adverse reproductive actions of BPA observed in different parts of the world.


Using genetic loci to understand the relationship between adiposity and psychological distress: a Mendelian Randomization study in the Copenhagen General Population Study of 53,221 adults.
We used genetic variants that are robustly associated with adiposity to examine the causal association of adiposity with psychological distress. We examined the association of adiposity with psychological distress in a large (N = 53,221) general population cohort of 20- to 99-year-old adults from Copenhagen, Denmark. Psychological distress was assessed using four questions that asked about: feeling stressed; not accomplishing very much; wanting to give up; and regular use of antidepressants/sedatives. We used the genetic loci FTO rs9939609 and MC4R rs17782313 as instrumental variables for adiposity quantified by body mass index (BMI) and waist to hip ratio (WHR). In conventional multivariable analyses, BMI and WHR were positively associated with distress. For example, the odds ratio of reporting not accomplishing for each additional standard deviation increase for BMI was 1.11 (95% CI: 1.09, 1.13) and for WHR was 1.10 (95% CI: 1.08, 1.13) in the fully adjusted analyses. In contrast, instrumental variable analyses showed an inverse association of adiposity on distress; corresponding odds ratio in instrumental variable analyses was 0.64 (95% CI: 0.46, 0.89) for BMI and 0.49 (95% CI: 0.25, 0.94) for WHR (P-values for difference between the two approaches both = 0.001). The inverse associations of adiposity and psychological distress when genetic variants are used as instrumental variables could be explained by biological pathways linking adiposity and distress. The positive associations of adiposity with distress in multivariable analyses might be explained by residual confounding or reverse causality.


Aminoglycoside toxicity--a survey of retinal specialists. Implications for ocular use.
Surveyed members of the Retina, Macula, and Vitreous Societies reported 93 cases of macular infarction they believed to be related to administration of gentamicin sulfate; five, to administration of amikacin sulfate; and three, to administration of tobramycin sulfate. Most cases of infarction after administration of gentamicin occurred in eyes that received an intravitreous injection of 0.4 mg after vitrectomy, but a surprisingly high number, 17, occurred after injection of 0.1 or 0.2 mg, doses that are considered safe by many ophthalmologists. Four additional cases of infarction occurred in eyes that did not undergo vitrectomy after injection of 0.1 or 0.2 mg. Four of the five cases related to administration of amikacin occurred after intravitreous injection of 0.4 mg, and one of these four occurred in an eye that did not undergo vitrectomy. Twenty-three cases of macular infarction occurred in eyes that were treated with prophylactic subconjunctival injections of aminoglycosides after routine ocular surgery. Responses from this survey suggest that aminoglycoside-induced retinal infarction is widely recognized and more common than indicated from the small number of cases reported in the literature. The role of aminoglycosides in the prophylaxis of ocular infections and the management of endophthalmitis should be reevaluated.


Gene expression in time and space: additive vs hierarchical organization of cis-regulatory regions.
In higher eukaryotes, individual genes are often intermingled with other genes and spread out across tens to hundreds of kilobases, even though only small portions of their sequence are devoted to protein coding. Yet, in this seemingly extended and tangled mess, the cell is able to precisely regulate gene expression in both time and space. Over the past few decades, numerous elements, like enhancers, silencers and insulators have been found that shed some light on how the precise control of gene expression is achieved. Through these discoveries, an additive model of gene expression was envisioned, where the addition of the patterning details imparted by regulatory elements would create the final pattern of gene expression. Although many genes can be described using this model, recent work in the Drosophila bithorax complex suggests that this model may be somewhat simplistic and, in fact, regulatory elements sometimes seem to communicate with each other to form a functional hierarchy that is far from additive.


Role played by purinergic receptors on muscle afferents in evoking the exercise pressor reflex.
The exercise pressor reflex is believed to be evoked, in part, by multiple metabolic stimuli that are generated when blood supply to exercising muscles is inadequate to meet metabolic demand. Recently, ATP, which is a P2 receptor agonist, has been suggested to be one of the metabolic stimuli evoking this reflex. We therefore tested the hypothesis that blockade of P2 receptors within contracting skeletal muscle attenuated the exercise pressor reflex in decerebrate cats. We found that popliteal arterial injection of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg), a P2 receptor antagonist, attenuated the pressor response to static contraction of the triceps surae muscles. Specifically, the pressor response to contraction before PPADS averaged 36 +/- 3 mmHg, whereas afterward it averaged 14 +/- 3 mmHg (P < 0.001; n = 19). In addition, PPADS attenuated the pressor response to postcontraction circulatory occlusion (P < 0.01; n = 11). In contrast, popliteal arterial injection of CGS-15943 (250 micro g/kg), a P1 receptor antagonist, had no effect on the pressor response to static contraction of the triceps surae muscles. In addition, popliteal arterial injection of PPADS but not CGS-15943 attenuated the pressor response to stretch of the calcaneal (Achilles) tendon. We conclude that P2 receptors on the endings of thin fiber muscle afferents play a role in evoking both the metabolic and mechanoreceptor components of the exercise pressor reflex.


Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. HIV Outpatient Study (HOPS) Investigators.
Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L. Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P=.004). Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.


Bewitching sex workers, blaming wives: HIV/AIDS, stigma, and the gender politics of panic in western Kenya.
Since access to HIV testing, counselling, and drug therapy has improved so dramatically, scholars have investigated ways this 'scale-up' has interacted with HIV/AIDS-related stigma in sub-Saharan Africa. Drawing on data collected during ethnographic research in a trading centre in western Kenya, this paper critically analyses two violent and localised case studies of panic over the ill health of particular community residents as a nuanced lens through which to explore the dynamic interplay of gender politics and processes of HIV/AIDS-related stigma in the aftershocks of the AIDS crisis. Gaining theoretical momentum from literatures focusing on stigma, gender, witchcraft, gossip, and accusation, we argue that the cases highlight collective anxieties, as well as local critiques of shifting gender roles and the strain of globalisation and legacies of uneven development on myriad forms of relationships. We further contend that these heightened moments of panic and accusation were deployments of power that ultimately sharpened local gender politics and conflicts on the ground in ways that complicated the social solidarity necessary to tackle social and health inequalities. The paper highlights one community's challenge to eradicate the stigma associated with HIV/AIDS during a period of increased access to HIV services.


Nucleotide sequence and structural organization of the small, broad-host-range plasmid pCI411 from Leuconostoc lactis 533.
The nucleotide sequence of the Leuconostoc lactis 533 cryptic plasmid pCI411 (2926 bp) was determined. Analysis revealed the presence of three open reading frames (ORFs). ORF 1 was capable of encoding a 24.9 kDa peptide which shared homology with the replication initiation protein (RepB) from a number of Gram-positive rolling circle plasmids. ORF 2 could encode a peptide of 6.6 kDa which was homologous to the RepC protein of the lactococcal plasmid pWV01. A function could not be assigned to ORF 3, which was capable of encoding a 12.1 kDa peptide. Transcription-translation analysis indicated the presence of three peptides of the predicted molecular masses. A putative double strand origin of replication (DSO) was identified which showed strong similarity with the DSO of a number of Gram-positive plasmids including pE194 from Staphylococcus. Structural analysis identified a number of direct and indirect repeats in addition to putative recombination-specific sites (RSA and RSB) in the non-coding region of pCI411. The observed characteristics suggest that this plasmid replicates using the rolling circle mechanism. pCI411, which could be introduced into Leuconostoc, Lactococcus, Streptococcus, Lactobacillus and Bacillus is the first plasmid from the genus Leuconostoc to be characterized in such detail.


Expression and function of Toll-like receptors in chicken heterophils.
The heterophil is the major polymorphonuclear cell in birds with a functional capacity akin to that of the mammalian neutrophil. Herein, we demonstrate that heterophils constitutively express TLR1/6/10, TLR2 type 1, TLR2 type 2, TLR3, TLR4, TLR5, and TLR7 mRNA. Furthermore, TLR agonists, including flagellin (from Salmonella typhimurium, FGN), peptidoglycan (from Staphylococcus aureus, PGN), ultra-pure lipopolysaccharide (from Salmonella minnesota, LPS), the synthetic double stranded RNA analog [poly(I:C)], and the guanosine analog, loxoribine (LOX) directly induced both an oxidative burst and a degranulation response. Interestingly, the synthetic bacterial lipoprotein Pam3CSK4 (palmitoyl-3-cysteine-serine-lysine-4, PAM) induced degranulation, but no oxidative burst. The bacterial TLR agonists (PAM, PGN, LPS, and FGN) all induced an up-regulation of expression of mRNA of the pro-inflammatory cytokines IL-1beta, IL-6, and IL-8; whereas both poly(I:C) and LOX induced a down-regulation of these cytokine mRNAs. Stimulation of heterophils with each specific TLR agonist led to a differential increase in the phosphorylation of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation, but not the phosphorylation of c-Jun NH2-terminal kinase (JNK). The broad TLR expression profile in heterophils reflects their principal role as first line effector cells in avian host defense against bacterial, viral, fungal, and parasitic infections. The results demonstrate the differential involvement of TLR-induced signals in the stimulation of transduction pathways that regulate the oxygen-dependent and -independent antimicrobial defense mechanisms of avian heterophils.


An in vitro evaluation of the antibacterial efficacy of chlorine dioxide on E. faecalis in bovine incisors.
This study investigated the ability of chlorine dioxide to eliminate Enterococcus faecalis from dentinal tubules of bovine incisors. Thirty-seven extracted bovine incisor roots were sectioned into seventy-four 5 mm disks. Standardized lumens were filled with either sterile Brain Heart Infusion Broth (contamination controls, n = 10) or BHI containing E. faecalis (1.0 x 10 cfu/ml). Disks were incubated in 5% CO2 at 37 degrees C for 72 h. To simulate endodontic instrumentation the lumens were again enlarged. Sixty disks were randomly divided into four experimental groups and filled with one of the following irrigants: 10% Clidox-S (chlorine dioxide), 13.8% BioClenz (chlorine dioxide), 5.25% Clorox, or saline. The disks were incubated for 30 min and were then frozen, pulverized, serially diluted in phosphate buffered saline, and plated on BHI plates in triplicate. Total colony forming units were counted macroscopically. Statistical analysis of the data was performed with a Kruskal-Wallis one-way ANOVA on ranks (p < 0.05, n = 60). Bacterial counts, expressed in log10 cfu/disk were as follows (">" denotes significant differences): Saline > Clidox-S = BioClenz > Clorox. All negative controls were sterile. Chlorine dioxide and NaOCL were both effective in eliminating E. faecalis from the dentinal disks within 30 min.


MRI hemodynamic markers of progressive bicuspid aortic valve-related aortic disease.
To determine the reproducibility of MRI aortic hemodynamic markers and to assess their relationship to aortic growth in a cohort of patients with bicuspid aortic valves (BAV). Twenty-five patients previously studied with four-dimensional (4D) Flow imaging who had at least two separate cross-sectional imaging studies to assess for aortic growth were included: tricuspid aortic valve (TAV) controls without valvular disease (n = 12) and patients with BAV (n = 13). Flow data from the ascending aorta was used for calculation of peak velocity, normalized flow displacement, maximum wall shear stress (WSS), mean WSS, and minimal WSS. Pearson's correlation was used to evaluate interobserver agreement, and linear regression to evaluate the correlation between the different hemodynamic markers and growth. Patient informed consent was waived by the institutional review board that approved the study. Peak velocity and flow displacement were very reproducible (r = 0.90-1.0 and r = 0.91-0.98, respectively). The range of WSS parameters was largely reproducible (0.47 < r < 0.96) with the greatest variability at the data extraction stage of analysis (0.47 < r < 0.85). Flow displacement best correlated with interval aortic growth (r = 0.65), peak velocity was moderately correlated (r = 0.35), but the WSS parameters did not correlate well with growth (r < 0.17). Flow displacement is a simple and reproducible hemodynamic marker that shows good correlation with aortic growth in patients with bicuspid aortic valves.


Choroidal malignant melanoma in an albino.
This is the first report of an amelanotic melanoma arising in the unpigmented choroid of a tyrosinase-positive oculocutaneous albino (TPOCA). Melanosomes within the tumour showed a maturation arrest in the unpigmented type II (premelanosome) phase. Other neural crest derived melanocytes in iris and choroid showed similar limited melanogenesis. The neuroectodermally derived melanocytes of the iris, ciliary body, and retinal pigment epithelium (RPE) contained mature melanosomes, though clinically the RPE was pale. The significance of this tumour arising in an albinotic eye is discussed.


The Impact of Advertisement Messaging on Enrollment of Young Men Who Have Sex With Men for Web-Based Research: Observational Study.
Recruiting young men who have sex with men (YMSM) in community settings is difficult. The use of Web-based social networks and dating apps for recruitment can be successful approaches, although little work has been done on the impact of study advertisement content on recruitment. The aim of this study was to evaluate the effects of advertisement message content on the recruitment of YMSM (aged 18-26 years) for a Web-based focus group study, examining perspectives and preferences for a mobile app that was designed to support sexual health among YMSM. Between March and April 2017, a recruitment campaign to promote human papillomavirus vaccination was launched on a popular social networking and dating app for YMSM, with 3 different text-based advertisement themes (technology, cancer prevention, and sexual innuendo). The campaign recruited YMSM across 3 states (Massachusetts, New York, and Pennsylvania). We examined the click-through rates, conversion rates, and enrollment rates of each of the advertisements and examined differences in views and clicks by age, state, and time of day. The sexual innuendo advertisement had the highest click rates when compared with both the technology (click rate ratio [CRR] 2.06, 95% CI 1.74-2.45) and cancer prevention (CRR 1.62, 95% CI 1.38-1.90) advertisements. The sexual innuendo advertisement also had higher study enrollment rates compared with the technology (CRR 1.90, 95% CI 1.23-2.83) and cancer prevention (CRR 2.06, 95% CI 1.37-3.13) advertisements. No differences were observed in clicks or enrollment by age, state, or time of day. Our marketing campaign, targeting YMSM, was effective in recruiting participants for a qualitative study, using Web-based focus groups. The sexual innuendo advertisement was the most effective and cost-efficient advertisement of the 3 approaches trialed. Different populations need different targeted strategies for study recruitment. Researchers should work with key representatives to develop and test culturally relevant messaging and approaches that utilize current and popular technologies.


New ages for the last Australian megafauna: continent-wide extinction about 46,000 years ago.
All Australian land mammals, reptiles, and birds weighing more than 100 kilograms, and six of the seven genera with a body mass of 45 to 100 kilograms, perished in the late Quaternary. The timing and causes of these extinctions remain uncertain. We report burial ages for megafauna from 28 sites and infer extinction across the continent around 46,400 years ago (95% confidence interval, 51,200 to 39,800 years ago). Our results rule out extreme aridity at the Last Glacial Maximum as the cause of extinction, but not other climatic impacts; a "blitzkrieg" model of human-induced extinction; or an extended period of anthropogenic ecosystem disruption.


Reproducibility and predictors of the apnea hypopnea index across multiple nights.
Attended polysomnography (PSG) is the standard diagnostic test for sleep apnea (SA). However, due to internight variability in SA, a single night PSG may not accurately reflect the true severity of SA. Although internight variability is a well-known phenomenon, its root causes have not been fully elucidated. The objective of this study was to determine factors associated with internight variability in the apnea-hypopnea index (AHI) and its magnitude in the home environment. Each participant had a full overnight PSG simultaneous with a validated portable sleep apnea monitoring device (BresoDx®) followed by two overnight home tests using the portable monitor only. Patients were stratified into those with variable AHI and consistent AHI (AHI difference ≥10 or <10 between any 2 nights, respectively). Demographics, sleepiness, sleep test variable, and supine-predominant SA (supine-SA) were examined for any association with variable AHI. Forty patients completed the protocol. The correlation between PSG and simultaneous BresoDx derived AHIs was 93.4%. Inter-class correlation between the three nights' AHIs was 89.2%. Over two-thirds (67.5%) of patients had consistent AHIs across the three nights while 32.5% had variable AHI. AHI variability was significantly associated with supine-SA (p=0.0014) and correlated with first night's AHI (r=0.664, p<0.001). None of the other variable, including BMI, sleepiness, gender, or test duration were associated with internight variability. Although portable monitoring was highly reproducible over three nights in the majority of participants, one third had a variable AHI. Supine-SA and high AHI on the first night were predictors of high internight variability.


Contribution of Mn-cofactored superoxide dismutase (SodA) to the virulence of Streptococcus agalactiae.
Superoxide dismutases convert superoxide anions to molecular oxygen and hydrogen peroxide, which, in turn, is metabolized by catalases and/or peroxidases. These enzymes constitute one of the major defense mechanisms of cells against oxidative stress and hence play a role in the pathogenesis of certain bacteria. We previously demonstrated that group B streptococci (GBS) possess a single Mn-cofactored superoxide dismutase (SodA). To analyze the role of this enzyme in the pathogenicity of GBS, we constructed a sodA-disrupted mutant of Streptococcus agalactiae NEM316 by allelic exchange. This mutant was subsequently cis complemented by integration into the chromosome of pAT113/Sp harboring the wild-type sodA gene. The SOD specific activity detected by gel analysis in cell extracts confirmed that active SODs were present in the parental and complemented strains but absent in the sodA mutant. The growth rates of these strains in standing cultures were comparable, but the sodA mutant was extremely susceptible to the oxidative stress generated by addition of paraquat or hydrogen peroxide to the culture medium and exhibited a higher mutation frequency in the presence of rifampin. In mouse bone marrow-derived macrophages, the sodA mutant showed an increased susceptibility to bacterial killing by macrophages. In a mouse infection model, after intravenous injection the survival of the sodA mutant in the blood and the brain was markedly reduced in comparison to that of the parental and complemented strains whereas only minor effects on survival in the liver and the spleen were observed. These results suggest that SodA plays a role in GBS pathogenesis.


Filamin is required for ring canal assembly and actin organization during Drosophila oogenesis.
The remodeling of the actin cytoskeleton is essential for cell migration, cell division, and cell morphogenesis. Actin-binding proteins play a pivotal role in reorganizing the actin cytoskeleton in response to signals exchanged between cells. In consequence, actin-binding proteins are increasingly a focus of investigations into effectors of cell signaling and the coordination of cellular behaviors within developmental processes. One of the first actin-binding proteins identified was filamin, or actin-binding protein 280 (ABP280). Filamin is required for cell migration (Cunningham et al. 1992), and mutations in human alpha-filamin (FLN1; Fox et al. 1998) are responsible for impaired migration of cerebral neurons and give rise to periventricular heterotopia, a disorder that leads to epilepsy and vascular disorders, as well as embryonic lethality. We report the identification and characterization of a mutation in Drosophila filamin, the homologue of human alpha-filamin. During oogenesis, filamin is concentrated in the ring canal structures that fortify arrested cleavage furrows and establish cytoplasmic bridges between cells of the germline. The major structural features common to other filamins are conserved in Drosophila filamin. Mutations in Drosophila filamin disrupt actin filament organization and compromise membrane integrity during oocyte development, resulting in female sterility. The genetic and molecular characterization of Drosophila filamin provides the first genetic model system for the analysis of filamin function and regulation during development.


Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults.
Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune) or the corresponding brand formulations (Epivir, Zerit, and Viramune). An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC(0-12h) and C(max). Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8-1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine C(max), 1.3 (0.99-1.71) and AUC(0-12h), 1.1 (0.87-1.38); lamivudine C(max), 0.8 (0.63-0.98) and AUC(0-12h), 0.8 (0.65-0.99); and nevirapine C(max), 1.1 (0.95-1.23) and AUC(0-12h), 1.1 (0.95-1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical.


Inhalation of welding fumes reduced sperm counts and high fat diet reduced testosterone levels; differential effects in Sprague Dawley and Brown Norway rats.
Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m3 of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7-12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24). At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet. Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.


The cost of a knowledge silo: a systematic re-review of water, sanitation and hygiene interventions.
Divisions between communities, disciplinary and practice, impede understanding of how complex interventions in health and other sectors actually work and slow the development and spread of more effective ones. We test this hypothesis by re-reviewing a Cochrane-standard systematic review (SR) of water, sanitation and hygiene (WASH) interventions' impact on child diarrhoea morbidity: can greater understanding of impacts and how they are achieved be gained when the same papers are reviewed jointly from health and development perspectives? Using realist review methods, researchers examined the 27 papers for evidence of other impact pathways operating than assumed in the papers and SR. Evidence relating to four questions was judged on a scale of likelihood. At the 'more than possible' or 'likely' level, 22% of interventions were judged to involve substantially more actions than the SR's label indicated; 37% resulted in substantial additional impacts, beyond reduced diarrhoea morbidity; and unforeseen actions by individuals, households or communities substantially contributed to the impacts in 48% of studies. In 44%, it was judged that these additional impacts and actions would have substantially affected the intervention's effect on diarrhoea morbidity. The prevalence of these impacts and actions might well be found greater in studies not so narrowly selected. We identify six impact pathways suggested by these studies that were not considered by the SR: these are tentative, given the limitations of the literature we reviewed, but may help stimulate wider review and primary evaluation efforts. This re-review offers a fuller understanding of the impacts of these interventions and how they are produced, pointing to several ways in which investments might enhance health and wellbeing. It suggests that some conclusions of the SR and earlier reviews should be reconsidered. Moreover, it contributes important experience to the continuing debate on appropriate methods to evaluate and synthesize evidence on complex interventions.


A comparative evaluation of gene transfer into blood cells using the same retroviral backbone for independent expression of the EGFP and deltaLNGFR marker genes.
Retroviral vectors are widely used to deliver foreign genes to hematopoietic stem cells (HSC). Improvement of marking protocols needs reporter genes to allow rapid detection and efficient selection of transduced cells. The great potential of EGFP and LNGFR as reporter systems prompted us to compare them simultaneously, using the same retroviral backbone and the same gene transfer procedures. The EGFP and LNGFR coding sequences were separately cloned into the MFG retroviral backbone. A cloning strategy assuring that both genes utilize the same ATG as the start codon was adopted. Marker gene expression, viral titers, transduction efficiency, and vector stability were evaluated in expanded amphotropic packaging clones and human hematopoietic cell lines by flow cytometry and PCR analysis. Vectors were also tested for their ability to transduce CD34+ peripheral blood cells. A significantly larger number of MFG- LNGFR packaging clones were obtained that produced high viral titers. A direct correlation between viral titer and marker gene expression in packaging clones was demonstrated for both constructs. Similar expression kinetics and absence of in vitro toxicity in transduced cells were also observed for both constructs. Successful infection of CD34+ cells was achieved even after a short time of exposure to recombinant viruses. Our results demonstrate that EGFP and LNGFR marker genes are equally useful for a rapid, specific and non-toxic detection of transduced cells. The MFG-EGFP construct appears useful to optimize gene transfer protocols in vitro. On the other hand, the MFG-LNGFR construct, for making possible a more efficient selection of high titer producer clones, as well as for safety and adaptability to the in vivo use, is more suitable for clinical applications.


Partnering for health: collaborative leadership between a community health center and the YWCA central Massachusetts.
A collaborative partnership among community-based organizations (CBOs)-a community-health center, a YWCA, and 2 academic health centers-developed and implemented open access to physical activity for health center patients. To describe partnership approach taken by 2 CBOs; determine staffs' views of this unique partnership, highlight aspects of the partnership that contributed to its success, identify challenges and mechanisms for overcoming them, and note lessons learned. Assess health center patients' use of YWCA facility. Usage data were obtained from YWCA records. Staff were interviewed using primarily open-ended questions. Inductive approach was used to analyze qualitative data. The approach to partnership was largely organic, without formal working documents; nevertheless, the partnership reflected the organizations' missions. Over 4 years, 1134 health center patients made more than 23 000 visits to the YWCA. Responses of health center staff and provider interviewees about partnership processes sorted into the following categories: partnership description and results, partnership benefits, challenges, lessons learned, and advice to other CBOs. YWCA staff interviewee responses reflected the categories: staffing, clientele, and public face. Comments also included challenges, lessons learned, and advice to other YWCAs. This partnership achieved notable successes largely because (a) it formed to serve a specific purpose that met both agencies' goals, (b) leaders made sustained commitments, and (c) it managed conflict. The partnership has taken on new projects over time; new ideas for improving access and service to underserved patients continue to emerge. Interorganizational trust and allegiance have been key to addressing challenges; nevertheless, the organic nature of the partnership's origins and the challenges of success have meant that the partnership has restructured its agreement and, to avoid being overwhelmed, limited new patient use.


Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.
Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.


Hydrogen Assisted Cracking in Pearlitic Steel Rods: The Role of Residual Stresses Generated by Fatigue Precracking.
Stress corrosion cracking (SCC) of metals is an issue of major concern in engineering since this phenomenon causes many catastrophic failures of structural components in aggressive environments. SCC is even more harmful under cathodic conditions promoting the phenomenon known as hydrogen assisted cracking (HAC), hydrogen assisted fracture (HAF) or hydrogen embrittlement (HE). A common way to assess the susceptibility of a given material to HAC, HAF or HE is to subject a cracked rod to a constant extension rate tension (CERT) test until it fractures in this harsh environment. This paper analyzes the influence of a residual stress field generated by fatigue precracking on the sample's posterior susceptibility to HAC. To achieve this goal, numerical simulations were carried out of hydrogen diffusion assisted by the stress field. Firstly, a mechanical simulation of the fatigue precracking was developed for revealing the residual stress field after diverse cyclic loading scenarios and posterior stress field evolution during CERT loading. Afterwards, a simulation of hydrogen diffusion assisted by stress was carried out considering the residual stresses after fatigue and the superposed rising stresses caused by CERT loading. Results reveal the key role of the residual stress field after fatigue precracking in the HAC phenomena in cracked steel rods as well as the beneficial effect of compressive residual stress.


Pattern recognition with wavelength-multiplexed filters.
Wavelength-multiplexed matched spatial filters are used in an incoherent optical pattern recognition system. The system produces color-coded correlation responses which allow the simultaneous recognition of several objects and, in addition, reduces the requirements on filter positioning devices. Analysis of the system, comparison with previous systems, experimental results, and discussions are given.


A cohort study of cigarette smoking and risk of fibroadenoma.
This cohort study examines the association between cigarette smoking and risk of fibroadenoma. The study was conducted among the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomised, controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) Cases were the 222 women who were diagnosed with biopsy-confirmed incident fibroadenoma. For comparative purposes, a subcohort, consisting of a random sample of 5,681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 222 cases and 5,488 non-cases. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using Poisson regression. Cigarette smoking was associated with reduced risk of fibroadenoma, the IRR (95% CI) for more than 550 cigarette-years of exposure being 0.66 (0.40-1.10). Although the reduction in risk was evident for all smokers combined (ex-smokers and current smokers), it was indicative largely of an inverse association in current smokers, in whom the IRR (95% CI) for > 300 cigarette-years of exposure was 0.49 (0.24-0.98). The results were mostly the same when examined in strata defined by method of detection of fibroadenoma, menopausal status and history of previous breast disease. There was no evidence for a reduction in risk with time since last use of cigarettes. The results of this study suggest that cigarette smoking is associated with reduced risk of fibroadenoma, especially in current smokers.


Refined radiation hybrid map of mouse chromosome 17.
We have made a radiation hybrid map of mouse Chromosome (Chr) 17 with 75 microsatellite markers, including those from McCarthy et al. (Genome Res 7, 1153-1161, 1997). Seventy-four of the markers are linked at LOD > 9, and all link at LOD > 5. A LOD 3 framework of 18 markers was used to construct a placement map. The order obtained is in good agreement with genetic maps, and distance estimates give an idea of how recombination rates vary across the chromosome. Recombination is remarkably low with respect to RH break frequency in the region from the centromere to the end of H2. This is similar in interspecific and intersubspecific crosses despite the inversion of a substantial part of this region in Mus spretus with respect to Mus musculus.


Bacteriocins from Lactobacillus plantarum - production, genetic organization and mode of action: produção, organização genética e modo de ação.
Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented.


Gender-related differences in etiology of organic central precocious puberty.
Central precocious puberty (CPP) is idiopathic in 90% of girls and 60% of boys, while some cases are caused by lesions of central nervous system (CNS), a condition often referred to as organic CPP. We aimed to analyze the etiology of organic CPP in a large cohort of girls and boys and determine gender-related differences. Medical files of 256 girls and 120 boys diagnosed and treated for CPP in a single center in the last two decades were reviewed. Patients were classified into four groups with respect to previous history and MRI findings: (1) previously established CNS pathology at the time of diagnosis, (2) novel CNS pathology previously asymptomatic, (3) incidentalomas considered to be unrelated to CPP, and (4) completely normal MRI. Group 1 and 2 were considered as organic CPP whereas group 3 and 4 were considered as idiopathic CPP. Prevalence of CNS pathology was significantly higher in boys than girls (21.7% vs 6.2%). Previous CNS pathologies such as developmental anomaly of CNS, parenchymal injury, necrotic lesions and hydrocephalus were present in 3.5% of girls and 8.3% of boys. Prevalence of novel CNS pathology as determined by imaging among neurologically asymptomatic patients was 2.8% in girls and 14.5% in boys. The most common novel CNS pathologies in boys were hamartomas (5%) and suprasellar arachnoid cysts (3.3%); which were significantly lower in girls (0.8 and 0.8% respectively). Onset of organic CPP was before six years in girls, and seven years in boys. Organic CPP was 3.5 times more common in boys compared to girls. It is possible to detect an underlying CNS pathology in one out of every five boys with CPP. Frequency and distribution of organic etiology also differ between girls and boys, hypothalamic hamartomas and suprasellar arachnoid cysts being more common in boys than girls. The likelihood of novel intracranial pathology associated with CPP is quite low in girls with an onset after six years of age and in boys with an onset after seven years of age.


Emotional Burden and Perceived Social Support in Male Partners of Women with Cancer.
The aim of this study was to describe the correlations between the psychosocial burden on male caregivers and their perception of social support, as well as distress, anxiety, and depression among their partners in the first six months after a cancer diagnosis. A cross-sectional, longitudinal and observational study was conducted on a group of 61 couples, with the use of Zarit Burden Interview (ZBI), Caregiver Burden Scale (CBS), Berlín Social Support Scales (BSSS), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). Statistical analysis was performed using Statistica v.13. A strong positive correlation between the ZBI and CBS, as well as between support-seeking and the emotional involvement of male partners, was documented. The negative correlation between the lack of instrumental support and a much greater burden on caregivers, in emotional, social, and family life was documented. The level of distress, anxiety, and depression, as well as family problems reported by female patients, were positively correlated with the male caregiver's burden. A demographic analysis showed significant relationships between the number of offspring and the negative health indicators of patients and their partners. The obtained results encourage deeper reflection on the need to improve the availability of instrumental support for male caregivers and support for families with an oncological ill parent in caring for minor children, and to maintain the social activity of the caregiver.


General Practitioners' vitamin K antagonist monitoring is associated with better blood pressure control in patients with hypertension--a cross-sectional database study.
Patients requiring anticoagulation suffer from comorbidities such as hypertension. On the occasion of INR monitoring, general practitioners (GPs) have the opportunity to control for blood pressure (BP). We aimed to evaluate the impact of Vitamin-K Antagonist (VKA) monitoring by GPs on BP control in patients with hypertension. We cross-sectionally analyzed the database of the Swiss Family Medicine ICPC Research using Electronic Medical Records (FIRE) of 60 general practices in a primary care setting in Switzerland. This database includes 113,335 patients who visited their GP between 2009 and 2013. We identified patients with hypertension based on antihypertensive medication prescribed for ≥ 6 months. We compared patients with VKA for ≥ 3 months and patients without such treatment regarding BP control. We adjusted for age, sex, observation period, number of consultations and comorbidity. We identified 4,412 patients with hypertension and blood pressure recordings in the FIRE database. Among these, 569 (12.9%) were on Phenprocoumon (VKA) and 3,843 (87.1%) had no anticoagulation. Mean systolic and diastolic BP was significantly lower in the VKA group (130.6 ± 14.9 vs 139.8 ± 15.8 and 76.6 ± 7.9 vs 81.3 ± 9.3 mm Hg) (p < 0.001 for both). The difference remained after adjusting for possible confounders. Systolic and diastolic BP were significantly lower in the VKA group, reaching a mean difference of -8.4 mm Hg (95% CI -9.8 to -7.0 mm Hg) and -1.5 mm Hg (95% CI -2.3 to -0.7 mm Hg), respectively (p < 0.001 for both). In a large sample of hypertensive patients in Switzerland, VKA treatment was independently associated with better systolic and diastolic BP control. The observed effect could be due to better compliance with antihypertensive medication in patients treated with VKA. Therefore, we conclude to be aware of this possible benefit especially in patients with lower expected compliance and with multimorbidity.


Anticoagulation for atrial fibrillation after intracranial hemorrhage: A systematic review.
We summarize the existing evidence on the potential benefit of oral anticoagulation (OAC) in intracerebral hemorrhage (ICH) survivors with nonvalvular atrial fibrillation (NVAF). Systematic review of the literature to address the following issues: (1) prevalence of NVAF in ICH survivors, (2) current prescription of OAC, (3) factors associated with resumption of OAC, (4) risk of ischemic stroke (IS) and recurrent ICH, and (5) ideal timing for restarting OAC in ICH survivors with NVAF. After screening 547 articles, 26 were included in the review. Only 3 focused specifically on patients with ICH as primary event, NVAF as indication for OAC, and recurrent ICH and IS as primary endpoints. In addition, 19 letters to the editor/reviews/editorials/experts' surveys/experts' opinion were used for discussion purposes. NVAF is highly prevalent among ICH survivors. The risks of IS, recurrent ICH, and mortality are heightened in this group. Most published data show a net benefit in terms of IS prevention and mortality when anticoagulation is restarted. However, those studies are observational and mostly retrospective, therefore selection bias may play a major role in the results observed in these cohorts. Only randomized controlled trials, either pragmatic or explanatory, can provide more conclusive answers for this important clinical question.


A mutation-specific, single-arm, phase 2 study of dovitinib in patients with advanced malignancies.
Receptor tyrosine kinases (RTKs) play key roles in tumorigenesis. The multi-RTK inhibitor dovitinib has demonstrated promising antitumor activity in multiple cancers. In this phase 2, open-label, single-arm study, patients with advanced malignancies with RTK-pathway genetic aberrations whose disease progressed on/following standard treatment received dovitinib (500 mg/day; 5-days-on/2-days-off). The primary endpoint was clinical benefit rate (CBR; complete response, partial response [PR], or stable disease [SD] for ≥ 16 weeks). Of 80 patients enrolled, common tumors included gastrointestinal stromal tumors (GIST; 20.0%), colorectal cancer (CRC; 18.8%), and ovarian cancer (10.0%). Patients were heavily pretreated (median prior lines = 4; 67.5% had ≥ 3 prior lines). Genetic aberrations included cKIT (28.8%), FGFR3 (15.0%), and RET (15.0%). The CBR was 13.8%; one PR (GIST) and 10 SD (adenoid cystic [n = 3]; ovarian [n = 3]; GIST [n = 2]; CRC [n = 1]; gastroesophageal junction [n = 1]). The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting. In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy. A subset of patients with RTK pathway-activated tumors experienced clinical benefit. However, the primary endpoint was not met, suggesting further refinement of predictive biomarkers is required.


Maximum-likelihood multiresolution laser radar range imaging.
Maximum-likelihood range imaging is considered for pulsed-imager operation of a coherent laser radar. The expectation-maximization (EM) algorithm is used to develop an explicit procedure for maximum-likelihood fitting of a multiresolution (wavelet) basis-at a sequence of increasingly fine resolutions-to laser radar range data. Specialization to the Haar-wavelet basis yields a procedure that is both computationally efficient and numerically robust. Basic analytical properties of the estimation algorithm and its performance are presented, along with results based on simulated and real laser radar range data. It is shown that the weights associated with the expectation-maximization iterations provide a reliable indicator for terminating the coarse-to-fine resolution progression. At the weight-determined stopping point, estimation performance approaches the ultimate limit set by the complete-data bound.


Micronutrients intake is associated with improved sperm DNA quality in older men.
To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men. Cross-sectional study design with equalized assignments into age groups. National laboratory and university. Nonclinical group of 22-80-year-old nonsmoking men (n = 80) who reported no fertility problems. Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay). Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed. Men with higher dietary and supplement intake of certain micronutrients may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage.


Perioperative factors that contribute to postoperative pain and/or nausea and vomiting in ambulatory laparoscopic surgery.
Both postoperative pain and postoperative nausea and vomiting are major factors that determine the time and quality of recovery in laparoscopic surgery. To determine the perioperative factors that contribute to the appearance of postoperative pain and postoperative nausea and vomiting in outpatient laparoscopic surgery. A prospective study was conducted on a cohort of 297 patients undergoing laparoscopic ambulatory surgery. A record was made of preoperative factors (usual medication, anaesthetic risk, etc.), intraoperative (surgical and anaesthetic times, drugs, CO2 pressure, etc.), and postoperative factors (major and minor complications, recovery times, etc.). As dependent variables, the postoperative symptoms considered were, nausea, vomiting, and/or postoperative pain. Considering as a combined variable the occurrence of níusea, vomiting or moderate/severe pain (4 or more points on a visual analogue scale), one or more of these symptoms occurred in 58.7% of the patients (95% CI: 52.8-64.4). Using a logistic regression, the variables associated with the appearance of symptoms were: female gender (OR: 3.4), waiting time over 45minutes prior to surgery (OR: 4.9) and no anti-emetic prophylaxis (OR: 12.2). In patients undergoing ambulatory laparoscopic surgery, one in 4had postoperative nausea and vomiting, and approximately half of moderate-intensity pain before discharge. Considering the overall the occurrence of pain and/or postoperative níusea and vomiting, these symptoms affect more than half of the patients being operated on, and are more frequent in women and in those who have to wait to access the operating room.


What are the ethical aspects surrounding the collegial decisional process in limiting and withdrawing treatment in intensive care?
The decision to limit or withdraw life-support treatment is an integral part of the job of a physician working in the intensive care unit, and of the approach to care. However, this decision is influenced by a number of factors. It is widely accepted that a medical decision that will ultimate lead to end-of-life in the intensive care unit (ICU) must be shared between all those involved in the care process, and should give precedence to the patient's wishes (either directly expressed by the patient or in written form, such as advance directives), and taking into account the opinion of the patient's family, including the surrogate if the patient is no longer capable of expressing themselves. A number of questions still remain unanswered regarding how decisions to limit or withdraw treatment are taken in daily practice, especially when this decision can be anticipated. We discuss here the collegial procedure for decision-making, in particular in the context of recent French legislation on end-of-life issues. We describe how collegial decision-making procedures should be carried out, and what points are covered in shared discussions regarding decisions to limit or withdraw life-sustaining therapies.


Intracellular acidification is required for full activation of the sweet taste receptor by miraculin.
Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.


Impact of plasma volume status on mortality following left ventricular assist device implantation.
Worsening systemic congestion is often the central trigger of hospitalization in patients with heart failure. However, accurate assessment of congestion is challenging. The prognostic impact of systemic congestion following durable continuous-flow left ventricular assist device (LVAD) implantation remains unknown. Consecutive patients who received durable continuous-flow LVAD implantation between January 2014 and June 2017 and were followed for 1 year were included. The association of preoperative plasma volume status, which was calculated using patients' body weight and hematocrit and expressed as a deviation from ideal plasma volume, with 1-year mortality following LVAD implantation was investigated. In total, 186 patients (median 57 years and 138 males) were included. Baseline plasma volume status was -30.1% (-37.1%, -19.4%) on median. Eighty-eight patients (47%) had higher plasma volume status (>-29.8%), and their 1-year survival was significantly lower than those without (67% vs. 87%, P = .001). High plasma volume status was an independent predictor of 1-year death with an adjusted hazard ratio of 4.52 (95% confidence interval 1.52-13.5). Baseline systemic congestion, as defined by the high plasma volume status, was associated with higher mortality following durable continuous-flow LVAD implantation. The implication of improving preoperative plasma volume remains an area of needed investigation.


Subcutaneous steroid injection as treatment for chalazion: prospective case series.
To study the efficacy of subcutaneous steroid injection in the treatment of chalazion. Prospective consecutive case series. University teaching hospital, Hong Kong. Patients with chalazion presenting to the out-patient clinic of the Department of Ophthalmology at the Prince of Wales Hospital from January to June 1998. Size of the chalazion after steroid injection treatment. Forty-eight consecutive patients with chalazion were treated with injection of triamcinolone into the subcutaneous tissue around the lesion. In 43 (89.6%) patients, the lesion subsided completely. Twenty-six (54.2%) patients had lesions that subsided with one injection. The size and duration of the chalazion at presentation did not significantly affect the outcome of the treatment. Two patients developed depigmentation of the skin at the site of injection. No other major complications were encountered. Subcutaneous injection of the steroid triamcinolone acetonide appears to be a simple and effective treatment for chalazion. Further comparative clinical trials are indicated.


Lack of association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence.
About 25,000 serious methamphetamine abusers live in the Czech Republic among the total population of 10 million. Dependence on methamphetamine is markedly related to the brain neurotransmitter dopamine, metabolised by catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain whether the Val158Met catechol-O-methyltransferase gene polymorphism is associated with methamphetamine dependence in this Central European country. One hundred and twenty-three subjects dependent on methamphetamine (women N=44), parents of sixty-seven dependent individuals, and four hundred healthy controls (women N=250) were involved into the study. We performed a population-based as well as family-based genetic association studies. We did not find any significant association between the Val158Met catechol-O-methyltransferase gene polymorphism and methamphetamine dependence using the population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED program, Version 3.1.4, respectively). We found a trend toward a statistically significant difference between the Val allele carriers and Met/Met homozygotes in the frequence of psychotic symptoms induced by methamphetamine (more frequent in Val carriers; p=0.062; Chi-Square Test). Further research involving haplotype analysis and other dopamine-related genetic polymorphisms in large populations is needed. More attention should also be paid to possible role of the Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical subtypes of dependence on methamphetamine involving e.g. psychotic features or violence.


Approaches to facilitate institutional review board approval of multicenter research studies.
Gaining Institutional Review Board (IRB) approval for a multicenter research study can be a lengthy and time-consuming process. It can increase the complexity of consent forms, decreasing patient understanding and lowering recruitment numbers. It also leads to increased costs through the duplication of effort. This paper examines some of the strategies used to streamline the IRB review process for multicenter studies and provides examples used by 2 existing multicenter comparative effectiveness research networks. A literature search was conducted to identify sources that described the challenges and potential strategies to facilitate multicenter IRB approval. The most promising avenues were identified and included in this review. Phone interviews were conducted with the Principal Investigators and Project Managers of 2 successful multicenter research networks to learn their "keys to success" and their lessons learned. Three strategies were identified that held the most promise: working with IRBs before submission, the use of central and/or federated IRBs, and the establishment of an umbrella protocol. Each of these strategies was used to some degree by the case study projects. Although the approaches documented here can help streamline the IRB approval process, they are not a "silver bullet." Because some of these approaches are still relatively new, empirical data are sparse. However, it is believed that they will significantly reduce the administrative burden of the project as a whole and lead to a decrease in the overall time to protocol approval.


Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams.
Listeria monocytogenes is an important food-borne bacterial pathogen and listeriosis can result in abortions in pregnant women. The bacterium can colonize food-processing environments, where specific molecular subtypes can persist for years. The purpose of this study was to determine the virulence potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10 % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlA(m*) (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas the maternofetal control was found in 6 % of fetal tissue samples. As the food-processing persistent strains carry a premature stop codon in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we hypothesize that listerial crossing of the placental barrier can occur by a mechanism that is independent of an interaction between E-cadherin and InlA.


Acoustic scattering in dispersions: improvements in the calculation of single particle scattering coefficients.
Measurements of ultrasound speed and attenuation can be related to the properties of dispersed systems by applying a scattering model. Rayleigh's method for scattering of sound by a spherical object, and its subsequent developments to include viscous, thermal, and other effects (known as the ECAH model) has been widely adopted. The ECAH method has difficulties, including numerical ill-conditioning, calculation of Bessel functions at large arguments, and inclusion of thermal effects in all cases. The present work develops techniques for improving the ECAH calculations to allow its use in instrumentation. It is shown that thermal terms can be neglected in some boundary equations up to approximately 100 GHz in water, and several simplified solutions result. An analytical solution for the zero-order coefficient is presented, with separate nonthermal and thermal parts, allowing estimation of the thermal contribution. Higher orders have been simplified by estimating the small shear contribution as the inertial limit is approached. The condition of the matrix solutions have been greatly improved by these techniques and by including appropriate scaling factors. A method is presented for calculating the required Bessel functions when the argument is large (high frequency or large particle size). The required number of partial wave orders is also considered.


Pharmacokinetics of Drug Entry into Cochlear Fluids.
The inner ear is exposed to aminoglycosides or other drugs either intentionally or as a side effect of clinical treatments directed at other regions of the body. An understanding of the effects of drugs on the inner ear requires knowledge of the pharmacokinetics of the drug once it reaches the cochlear fluids, specifically how much of it reaches different parts of the ear and how long it stays there before disappearing. Accumulating data show that drug distribution in the inner ear is complex, especially for drugs applied locally to the ear's round window membrane. Locally applied drugs do not disperse rapidly, but instead spread very slowly through the fluid spaces by diffusion so that substantial differences in drug concentration occur in different regions of the ear. In some cases, the drug may leak from the inner ear to the blood as fast as it diffuses, meaning it may never become uniformly distributed even when applied for a long period. In recent years, experimental pharmacokinetic studies have become increasingly quantitative, permitting the results to be interpreted with computer models. Simulations of the drug distribution in animals have been used as a basis to predict the likely drug distribution in the larger, human inner ear. Such studies allow clinical drug delivery protocols to be optimized to minimize inadvertent hearing loss and to deliver therapeutic levels of the drug more effectively.


Spatial correlation properties of focused partially coherent vortex beams.
The spatial correlation properties in the geometrical focal region of a converging, partially coherent vortex wave field are analyzed. Expressions are derived for a pair of points on the axis of symmetry and for a pair of points in the focal plane. It is found that the longitudinal and transverse coherence lengths in the focal region change with the variation of the topological charge and the normalized coherence length of the vortex field. In addition, the degree of coherence is shown to possess phase singularities.


Evaluation of the Protective Effect of Olive Leaf Extract on Cisplatin-Induced Testicular Damage in Rats.
In the present investigation, the effect of olive leaf extract (OLE) on testicular damage induced in rats by an intraperitoneal injection of cisplatin (cis-diamminedichloroplatinum (CDDP)) at a dose of 5 mg/kg was tested. Rats were randomly divided into 4 groups: control, CDDP, OLE, and OLE + CDDP. After 5 days of CDDP treatment, body and testicular weights, histopathological alteration, and serum male sex hormone levels were determined. In addition to the biochemical and immunohistochemical changes in the testes, CDDP caused the disorganization of germinal epithelium and apoptosis by inducing Bax and inhibiting Bcl-2 protein expression. Testicular weights, catalase, serum testosterone, testicular enzymatic (including glutathione peroxidase, glutathione reductase, and superoxide dismutase) along with nonenzymatic (glutathione) antioxidants, and levels of luteinizing and follicle-stimulating hormones were significantly reduced in addition to a significant increase in testicular malondialdehyde and nitrite/nitrate levels when compared with the control group. OLE treatment markedly attenuated both biochemical and histopathological changes. The reproductive beneficial effects of OLE were mediated, at least partly, by inducing the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.


A spectrometer designed for 6.7 and 14.1 T DNP-enhanced solid-state MAS NMR using quasi-optical microwave transmission.
A Dynamic Nuclear Polarisation (DNP) enhanced solid-state Magic Angle Spinning (MAS) NMR spectrometer operating at 6.7 T is described and demonstrated. The 187 GHz TE(13) fundamental mode of the FU CW VII gyrotron is used as the microwave source for this magnetic field strength and 284 MHz (1)H DNP-NMR. The spectrometer is designed for use with microwave frequencies up to 395 GHz (the TE(16) second-harmonic mode of the gyrotron) for DNP at 14.1T (600 MHz (1)H NMR). The pulsed microwave output from the gyrotron is converted to a quasi-optical Gaussian beam using a Vlasov antenna and transmitted to the NMR probe via an optical bench, with beam splitters for monitoring and adjusting the microwave power, a ferrite rotator to isolate the gyrotron from the reflected power and a Martin-Puplett interferometer for adjusting the polarisation. The Gaussian beam is reflected by curved mirrors inside the DNP-MAS-NMR probe to be incident at the sample along the MAS rotation axis. The beam is focussed to a ~1 mm waist at the top of the rotor and then gradually diverges to give much more efficient coupling throughout the sample than designs using direct waveguide irradiation. The probe can be used in triple channel HXY mode for 600 MHz (1)H and double channel HX mode for 284 MHz (1)H, with MAS sample temperatures ≥85 K. Initial data at 6.7 T and ~1 W pulsed microwave power are presented with (13)C enhancements of 60 for a frozen urea solution ((1)H-(13)C CP), 16 for bacteriorhodopsin in purple membrane ((1)H-(13)C CP) and 22 for (15)N in a frozen glycine solution ((1)H-(15)N CP) being obtained. In comparison with designs which irradiate perpendicular to the rotation axis the approach used here provides a highly efficient use of the incident microwave beam and an NMR-optimised coil design.


Nonreciprocal homeostatic compensation in Drosophila potassium channel mutants.
Homeostatic control of intrinsic excitability is important for long-term regulation of neuronal activity. In conjunction with many other forms of plasticity, intrinsic homeostasis helps neurons maintain stable activity regimes in the face of external input variability and destabilizing genetic mutations. In this study, we report a mechanism by which Drosophila melanogaster larval motor neurons stabilize hyperactivity induced by the loss of the delayed rectifying K+ channel Shaker cognate B (Shab), by upregulating the Ca2+-dependent K+ channel encoded by the slowpoke (slo) gene. We also show that loss of SLO does not trigger a reciprocal compensatory upregulation of SHAB, implying that homeostatic signaling pathways utilize compensatory pathways unique to the channel that was mutated. SLO upregulation due to loss of SHAB involves nuclear Ca2+ signaling and dCREB, suggesting that the slo homeostatic response is transcriptionally mediated. Examination of the changes in gene expression induced by these mutations suggests that there is not a generic transcriptional response to increased excitability in motor neurons, but that homeostatic compensations are influenced by the identity of the lost conductance.NEW & NOTEWORTHY The idea that activity-dependent homeostatic plasticity is driven solely by firing has wide credence. In this report we show that homeostatic compensation after loss of an ion channel conductance is tailored to identity of the channel lost, not its properties.


Arm movements evoked by electrical stimulation in the motor cortex of monkeys.
Electrical stimulation of the motor cortex in monkeys can evoke complex, multijoint movements including movements of the arm and hand. In this study, we examined these movements in detail and tested whether they showed adaptability to differing circumstances such as to a weight added to the hand. Electrical microstimulation was applied to motor cortex using pulse trains of 500-ms duration (matching the approximate duration of a reach). Arm movement was measured using a high-resolution three-dimensional tracking system. Movement latencies averaged 80.2 ms. Speed profiles were typically smooth and bell-shaped, and the peak speed covaried with movement distance. Stimulation generally evoked a specific final hand position. The convergence of the hand from disparate starting positions to a narrow range of final positions was statistically significant for every site tested (91/91). When a weight was fixed to the hand, for some stimulation sites (74%), the evoked movement appeared to compensate for the weight in that the hand was lifted to a similar final location. For other stimulation sites (26%), the weight caused a significant reduction in final hand height. For about one-half of the sites (54%), the variation in movement of each joint appeared to compensate for the variation in the other joints in a manner that stabilized the hand in a restricted region of space. These findings suggest that at least some of the stimulation-evoked movements reflect relatively high-level, adaptable motor plans.


Microsatellite evidence for high frequency of multiple paternity in the marine gastropod Rapana venosa.
Inferring of parentage in natural populations is important in understanding the mating systems of a species, which have great effects on its genetic structure and evolution. Muricidae, a large group (approximately 1,600 species) of marine gastropods, are poorly investigated in patterns of multiple paternity and sperm competition based on molecular techniques. The veined Rapa whelk, Rapana venosa, a commercially important muricid species with internal fertilization, is an ideal species to study the occurrence and frequency of multiple paternity and to facilitate understanding of their reproductive strategies. We developed five highly polymorphic microsatellites in R. venosa and applied them to identify multiple paternity in 19 broods (1381 embryos) collected from Dandong, China. Multiple paternity was detected in 17 (89.5%) of 19 broods. The number of sires per brood ranged from 1 to 7 (4.3 on average). Of the 17 multiply sired broods, 16 (94.1%) were significantly skewed from equal paternal contributions, and had a dominant sire which was also dominant in each assayed capsule. Our results indicate that a high level of multiple paternity occurs in the wild population of R. venosa. Similar patterns of multiple paternity in the 2-6 assayed capsules from each brood imply that fertilization events within the body of a female occur mostly (but not entirely) as random draws from a "well-but-not-perfectly blended sperm pool" of her several mates. Strongly skewed distributions of fertilization success among sires also suggest that sperm competition and/or cryptic female choice might be important for post-copulatory paternity biasing in this species.


Super-resolution image transfer by a vortex-like metamaterial.
We propose a vortex-like metamaterial device that is capable of transferring image along a spiral route without losing subwavelength information of the image. The super-resolution image can be guided and magnified at the same time with one single design. Our design may provide insights in manipulating super-resolution image in a more flexible manner. Examples are given and illustrated with numerical simulations.


Pregnant Women's Reasons for and Experiences of Visiting Antiabortion Pregnancy Resource Centers.
The primary mission of pregnancy resource centers is to dissuade women from choosing abortion. Reproductive health and rights advocates have asserted that these centers interfere in abortion decision making. However, the reasons pregnant women go to such centers and what they experience while there have not been examined. Between June 2015 and June 2017, in-depth, semistructured phone interviews were conducted with 21 pregnant women who had presented at prenatal care clinics in southern Louisiana and Baltimore, Maryland, and who had visited a pregnancy resource center. Topics covered in the interviews included reasons for visiting a center and the experience of the visit. Transcripts were analyzed first thematically and then using grounded theory. Most of the women were low income and had not been considering abortion when they visited a pregnancy resource center. Respondents reported that they had gone to these centers for pregnancy-related services, material goods and social support. They chose these centers because the resources were free, and they were largely satisfied with their experiences. Nonetheless, their receipt of services and goods was limited and often contingent on participation in the centers' activities. Pregnancy resource centers play a role in meeting the acute material and social needs of low-income pregnant women. However, the constraints on the resources the centers offer mean that this support cannot be part of a reliable system of care. Advocates and policymakers should take a nuanced approach to regulating these centers and consider the reasons women visit them, especially low-income women.


The ectomycorrhizal fungus Paxillus involutus converts organic matter in plant litter using a trimmed brown-rot mechanism involving Fenton chemistry.
Soils in boreal forests contain large stocks of carbon. Plants are the main source of this carbon through tissue residues and root exudates. A major part of the exudates are allocated to symbiotic ectomycorrhizal fungi. In return, the plant receives nutrients, in particular nitrogen from the mycorrhizal fungi. To capture the nitrogen, the fungi must at least partly disrupt the recalcitrant organic matter-protein complexes within which the nitrogen is embedded. This disruption process is poorly characterized. We used spectroscopic analyses and transcriptome profiling to examine the mechanism by which the ectomycorrhizal fungus Paxillus involutus degrades organic matter when acquiring nitrogen from plant litter. The fungus partially degraded polysaccharides and modified the structure of polyphenols. The observed chemical changes were consistent with a hydroxyl radical attack, involving Fenton chemistry similar to that of brown-rot fungi. The set of enzymes expressed by Pa. involutus during the degradation of the organic matter was similar to the set of enzymes involved in the oxidative degradation of wood by brown-rot fungi. However, Pa. involutus lacked transcripts encoding extracellular enzymes needed for metabolizing the released carbon. The saprotrophic activity has been reduced to a radical-based biodegradation system that can efficiently disrupt the organic matter-protein complexes and thereby mobilize the entrapped nutrients. We suggest that the released carbon then becomes available for further degradation and assimilation by commensal microbes, and that these activities have been lost in ectomycorrhizal fungi as an adaptation to symbiotic growth on host photosynthate. The interdependence of ectomycorrhizal symbionts and saprophytic microbes would provide a key link in the turnover of nutrients and carbon in forest ecosystems.


Context-Sensitivity and Individual Differences in the Derivation of Scalar Implicature.
The derivation of scalar implicatures for the quantifier some has been widely studied to investigate the computation of pragmatically enriched meanings. For example, the sentence "I found some books" carries the semantic interpretation that at least one book was found, but its interpretation is often enriched to include the implicature that not all the books were found. The implicature is argued to be more likely to arise when it is relevant for addressing a question under discussion (QUD) in the context, e.g., when "I found some books" is uttered in response to "Did you find all the books?" as opposed to "Did you find any books?". However, most experimental studies have not examined the influence of context on some, instead testing some sentences in isolation. Moreover, no study to our knowledge has examined individual differences in the ability to utilize context in interpreting some, whereas individual variation in deriving implicatures for some sentences in isolation is widely attested, with alternative proposals attributing this variation to individual differences in cognitive resources (e.g., working memory) or personality-based pragmatic abilities (e.g., as assessed by the Autism-Spectrum Quotient). The current study examined how context influences the interpretation of some in a story-sentence matching task, where participants rated some statements ("I cut some steaks") uttered by one character, in response to another character's question (QUD) that established the implicature as relevant ("Did you cut all the steaks?") or irrelevant ("Did you cut any steaks?"). We also examined to what extent individuals' sensitivity to QUD is modulated by individual differences via a battery of measures assessing cognitive resources, personality-based pragmatic abilities, and language abilities (which have been argued to modulate comprehension in other domains). Our results demonstrate that QUD affects the interpretation of some, and reveal that individual differences in sensitivity to QUD are modulated by both cognitive resources and personality-based pragmatic abilities. While previous studies have argued alternatively for cognitive resources or personality-based pragmatic abilities as important for deriving implicatures for some in isolation, we argue that arriving at a context-sensitive interpretation for some depends on both cognitive and personality-based properties of the individual.


The related adhesion focal tyrosine kinase differentially phosphorylates p130Cas and the Cas-like protein, p105HEF1.
The related adhesion focal tyrosine kinase (RAFTK) is tyrosine-phosphorylated following beta1 integrin or B cell antigen receptor stimulation in human B cells. Two substrates that are tyrosine-phosphorylated following integrin ligation in B cells are p130(Cas) and the Cas family member human enhancer of filamentation 1 (HEF1), both of which can associate with RAFTK. In this report we observed that RAFTK was involved in the phosphorylation of these two proteins. While a catalytically active RAFTK was required for both p130(Cas) and HEF1, phosphorylation of p130(Cas), but not of HEF1, was dependent on an intact autophosphorylation site (Tyr402) on RAFTK. To determine if RAFTK phosphorylated p130(Cas) and HEF1 directly or through an intermediate, we assayed the ability of RAFTK and of a Tyr402 mutant to phosphorylate purified HEF1 and p130(Cas) domains. RAFTK was able to phosphorylate the substrate domains of both p130(Cas) and HEF1, but only the C-terminal domain of p130(Cas). Furthermore, Tyr402, which mediates the binding of RAFTK to c-Src kinase, was required for the phosphorylation of the C-terminal domain of p130(Cas). These data suggest that RAFTK itself is sufficient for HEF1 phosphorylation, whereas a cooperation between RAFTK and Src kinases is required for the complete phosphorylation of p130(Cas).