Use of long-distance migration patterns of an endangered species to inform conservation planning for the world's largest marine protected area.
Large marine protected areas (MPAs), each hundreds of thousands of square kilometers, have been set up by governments around the world over the last decade as part of efforts to reduce ocean biodiversity declines, yet their efficacy is hotly debated. The Chagos Archipelago MPA (640,000 km(2) ) (Indian Ocean) lies at the heart of this debate. We conducted the first satellite tracking of a migratory species, the green turtle (Chelonia mydas), within the MPA and assessed the species' use of protected versus unprotected areas. We developed an approach to estimate length of residence within the MPA that may have utility across migratory taxa including tuna and sharks. We recorded the longest ever published migration for an adult cheloniid turtle (3979 km). Seven of 8 tracked individuals migrated to distant foraging grounds, often ≥1000 km outside the MPA. One turtle traveled to foraging grounds within the MPA. Thus, networks of small MPAs, developed synergistically with larger MPAs, may increase the amount of time migrating species spend within protected areas. The MPA will protect turtles during the breeding season and will protect some turtles on their foraging grounds within the MPA and others during the first part of their long-distance postbreeding oceanic migrations. International cooperation will be needed to develop the network of small MPAs needed to supplement the Chagos Archipelago MPA.


Shared parasitoids in a metacommunity: indirect interactions inhibit herbivore membership in local communities.
The interaction between species, mediated by a shared natural enemy (i.e., apparent competition), has been the subject of much theoretical and empirical investigation. However, we lack field experiments that assess the importance of apparent competition to metacommunity structure. Here, I conducted a series of field experiments to test whether apparent competition, mediated by shared egg parasitoids (Anagrus nigriventris and A. columbi), occurs between two abundant planthopper species (Delphacodes scolochloa and Prokelisia crocea) of the North American Great Plains. The two planthoppers feed on different plant species within prairie potholes (wet depressions) and, thus, do not interact directly. At the scale of individual potholes, a five-fold pulse increase in D. scolochloa density (relative to control potholes) resulted in a steady decline in P. crocea density over two generations. As expected in cases of apparent competition, P. crocea eggs in these potholes suffered twice the level of parasitism as P. crocea eggs in control potholes. In contrast, a sixfold increase in P. crocea density had no effect on D. scolochloa density or parasitism in those potholes. The superiority of D. scolochloa over P. crocea likely can be attributed to a larger source population size, greater amount of host habitat, and/or the presence of a phenological refuge from parasitism for D. scolochloa. In another experiment, in which small populations of P. crocea were established either in close proximity to D. scolochloa or in isolation, I found that the likelihood of P. crocea persistence was 36% lower in the former than the latter populations. This difference was attributable to very high rates of parasitism of P. crocea when adjacent to D. scolochloa. These two experiments provide clear evidence that the two planthopper species engage in apparent competition and that the shared parasitoids may play a significant role in limiting membership in a local community. Based on these findings, I argue that metacommunity studies must be broadened to include higher trophic levels.


Cranberry and urinary tract infections.
Urinary tract infection (UTI) refers to the presence of clinical signs and symptoms arising from the genitourinary tract plus the presence of one or more micro-organisms in the urine exceeding a threshold value for significance (ranges from 102 to 103 colony-forming units/mL). Infections are localized to the bladder (cystitis), renal parenchyma (pyelonephritis) or prostate (acute or chronic bacterial prostatitis). Single UTI episodes are very common, especially in adult women where there is a 50-fold predominance compared with adult men. In addition, recurrent UTIs are also common, occurring in up to one-third of women after first-episode UTIs. Recurrences requiring intervention are usually defined as two or more episodes over 6 months or three or more episodes over 1 year (this definition applies only to young women with acute uncomplicated UTIs). A cornerstone of prevention of UTI recurrence has been the use of low-dose once-daily or post-coital antimicrobials; however, much interest has surrounded non-antimicrobial-based approaches undergoing investigation such as use of probiotics, vaccines, oligosaccharide inhibitors of bacterial adherence and colonization, and bacterial interference with immunoreactive extracts of Escherichia coli. Local (intravaginal) estrogen therapy has had mixed results to date. Cranberry products in a variety of formulations have also undergone extensive evaluation over several decades in the management of UTIs. At present, there is no evidence that cranberry can be used to treat UTIs. Hence, the focus has been on its use as a preventative strategy. Cranberry has been effective in vitro and in vivo in animals for the prevention of UTI. Cranberry appears to work by inhibiting the adhesion of type I and P-fimbriated uropathogens (e.g. uropathogenic E. coli) to the uroepithelium, thus impairing colonization and subsequent infection. The isolation of the component(s) of cranberry with this activity has been a daunting task, considering the hundreds of compounds found in the fruit and its juice derivatives. Reasonable evidence suggests that the anthocyanidin/proanthocyanidin moieties are potent antiadhesion compounds. However, problems still exist with standardization of cranberry products, which makes it extremely difficult to compare products or extrapolate results. Unfortunately, most clinical trials have had design deficiencies and none have evaluated specific key cranberry-derived compounds considered likely to be active moieties (e.g. proanthocyanidins). In general, the preventive efficacy of cranberry has been variable and modest at best. Meta-analyses have established that recurrence rates over 1 year are reduced approximately 35% in young to middle-aged women. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism). The findings of the Cochrane Collaboration support the potential use of cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women. However, in light of the heterogeneity of clinical study designs and the lack of consensus regarding the dosage regimen and formulation to use, cranberry products cannot be recommended for the prophylaxis of recurrent UTIs at this time.


Focused ultrasound-triggered chemo-gene therapy with multifunctional nanocomplex for enhancing therapeutic efficacy.
Nanotechnology-based combination therapies, especially chemo-gene therapy, have been spotlighted as promising alternatives for cancer therapy. However, only a small amount of systemically administered nanomedicines reach the tumor site by the enhanced permeability and retention (EPR) effect, resulting in the limited therapeutic efficacy. Furthermore, the design of ideal drug delivery system for chemo-gene therapy has been impeded by the chemical and physical differences between nucleic acids and chemotherapeutics. Herein, we report a precisely designed nanocomplex which exhibits a focused ultrasound (FU)-responsive release and enhanced accumulation of released therapeutics to tumor site. After the nanocomplex composed of siRNA nanoparticles (siRNA-NP) and chemotherapeutics-loaded microbubbles was systemically injected, the nanocomplex was collapsed around the tumor tissue by FU exposure, and both siRNA-NP and chemotherapeutics were penetrated the dense extracellular matrix (ECM) of tumor site, leading to the enhanced chemo-gene therapeutic efficacy. The two-in-one nanocomplex is expected as a promising platform for combination therapy that can enhance the therapeutic efficiency of combination drugs at the cell and/or tissue levels with high drug loading ratio.


Use and impact of social prescribing: a mixed-methods feasibility study protocol.
Social prescribing aims to address social determinants of health, which account for 80%-90% of health outcomes, but the evidence base behind it is limited due to a lack of data linkingsocial prescribing activity and outcomes. The objective of the quantitative component of this feasibility studyisto identify the characteristics of individuals who receive social prescriptions and describe the use and estimate the impact of social prescribing; the latter will be done on a homeless subgroup. We will use the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care sentinel network, whose general practicescover a population of over 4 000 000 patients. Social prescribing data will be extracted onall recorded patients for 5 years up to 31 January 2020. The objective for the qualitative component of the study isto explore approaches to understand the contextual factors that will have influenced our quantitative findings to identify mechanisms to encourage adoption of social prescribing in primary care while improving data quality. Itwill comprise up to three 90-120 minute advisory group meetings for six to eight participants. Participants will be recruited based on their experience of delivering primary care within Oxfordshire and Surrey. The advisory group outputs will be analysed using framework analysis and will be used to create a survey instrument consisting of statements that surveyees, who will consist of primary care practitioners within the RCGP RSC, can agree or disagree with. All RCGP RSC data are pseudonymised at the point of data extraction. No personally identifiable data are required for this investigation. This protocol follows the Good Reporting of a Mixed Methods Study checklist. The study results will be published in a peer-reviewed journal and the dataset will be available to other researchers.


A cost-effectiveness analysis of fondaparinux sodium compared with enoxaparin sodium as prophylaxis against venous thromboembolism: use in patients undergoing major orthopaedic surgery.
To determine the cost effectiveness of fondaparinux sodium compared with enoxaparin sodium for prophylaxis against venous thromboembolism in patients undergoing major orthopaedic surgery. Using a cohort simulation model, two primary analyses were conducted from the perspective of the US healthcare payer. Probabilities for a trial-based analysis were obtained from patients participating in the fondaparinux clinical trial programme supplemented with data from published literature. Probabilities for a label-based analysis were estimated for a hypothetical cohort of US patients receiving either fondaparinux or enoxaparin as recommended by US FDA-approved labelling. Resource use and costs were obtained from large US healthcare databases. Outcome measures were rates of symptomatic thromboembolic events and healthcare costs. Costs were in 2003 values. In the trial-based analysis, fondaparinux was estimated to prevent 15.1 symptomatic venous thromboembolic events (per 1,000 patients) at 3 months for patients undergoing major orthopaedic surgery compared with enoxaparin. The cost savings (per patient) of using fondaparinux over enoxaparin are US 61 dollars at 30 days, US 89 dollars at 3 months, and US 155 dollars at 5 years. In the label-based analysis, fondaparinux was estimated to prevent 17.8 venous thromboembolic events (per 1,000 patients) at 3 months compared with enoxaparin, producing savings per patient of US 25 dollars at discharge, US 112 dollars over 1 month, US 141 dollars over 3 months and US 234 dollars over 5 years. Results remain robust to clinically plausible variation in input parameters and assumptions. Our model suggests that fondaparinux, when compared with the current standard regimen of enoxaparin for prophylaxis of venous thromboembolism in major orthopaedic surgery, improves outcomes and is cost saving from a US healthcare-payer perspective over the broad range of assumptions evaluated.


The role of competition and herbivory in biotic resistance against invaders: a synergistic effect.
Invasive species pose a major threat to global diversity, and once they are well established their eradication typically becomes unfeasible. However, certain natural mechanisms can increase the resistance of native communities to invaders and can be used to guide effective management policies. Both competition and herbivory have been identified as potential biotic resistance mechanisms that can limit plant invasiveness, but it is still under debate to what extent they might be effective against well-established invaders. Surprisingly, whereas biotic mechanisms are known to interact strongly, most studies to date have examined single biotic mechanisms separately, which likely influences our understanding of the strength and effectiveness of biotic resistance against invaders. Here we use long-term field data, benthic assemblage sampling, and exclusion experiments to assess the effect of native assemblage complexity and herbivory on the invasion dynamics of a successful invasive species, the alga Caulerpa cylindracea. A higher complexity of the native algal assemblage limited C. cylindracea invasion, probably through competition by canopy-forming and erect algae. Additionally, high herbivory pressure by the fish Sarpa salpa reduced C. cylindracea abundance by more than four times. However, long-term data of the invasion reflects that biotic resistance strength can vary across the invasion process and it is only where high assemblage complexity is concomitant with high herbivory pressure, that the most significant limitation is observed (synergistic effect). Overall, the findings reported in this study highlight that neglecting the interactions between biotic mechanisms during invasive processes and restricting the studied time scales may lead to underestimations of the true capacity of native assemblages to develop resistance to invaders.


Presence of cadmium residues in muscle, liver and kidney of Bubalus bubalis and histological evidence.
Cadmium (Cd) concentrations were evaluated in the samples of kidney, liver and muscle of sixty-six buffaloes regularly slaughtered. Forty were raised in Campania, in the territory between the province of Naples and Caserta and twenty-six were bred in Apulia, in the province of Bari. Two aliquots were prepared for the renal and hepatic samples: one intended for the chemical analysis and the other one intended for histological investigations. Muscle samples were the subject of purely chemical investigation. In the group of forty animals raised in the Campania region, the limits imposed by EC Reg. 1881/2006 and EC Reg. 488/2014 were exceeded in three renal samples, which showed values of 1.53, 1.22 and 1.1 mg/kg respectively; in three hepatic samples, which presented values of 0.72, 0.64 and 0.61 mg/kg, and in five muscle samples, with values of 0.16, 0.16, 0.09, 0.08 and 0.07, respectively. On the other hand, in the group of animals raised and slaughtered in the province of Bari, none of the twenty-six samples examined exceeded the limits imposed by the European regulations. The histological analysis showed typical, but not pathognomonic lesions in the renal samples from the animals raised in the provinces of Naples and Caserta. The levels of Cd contamination found in the samples examined suggest that it would be correct to exclude from the human consumption, as it happens for the equines, the kidney and the liver, especially from the animals raised in some geographical areas with a high rate of pollution.


Situational Use of Child Restraint Systems and Carpooling Behaviors in Parents and Caregivers.
Suboptimal compliance with child restraint system (CRS) recommendations can increase risk for injury or death in a motor vehicle crash. The purpose of this study was to examine scenarios associated with incomplete CRS use and non-use in children ages 4⁻10 years. We used a cross-sectional online survey with a convenience sample of parent/caregivers from the United States, age ≥18 years, with a child age 4⁻10 years in their home, who could read and spoke English, and drove child ≥6 times in previous three months. We used descriptive statistics and Mann-Whitney U to describe and compare the distribution of responses to situational use of CRSs among car seat users and booster seat users. We also used descriptive statistics and the Mann-Whitney U to describe and compare the distribution of responses to carpooling items among booster seat users and non-booster seat users. There were significant differences among those who reported most often using booster seats (n = 282) and car seats (n = 127) in situations involving rental cars, driving just around the corner, car too crowded to fit the CRS, not enough CRSs in the vehicle, the CRS is missing from the car, or the child is in someone else's car without a CRS (p < 0.05). Among those who reported most often using booster seats and who carpooled other children (n = 159), 71.7% (n = 114) always used a booster seat for their own child. When carpooling other children, booster seat users were significantly more likely to use booster seats for other children ages 4⁻10 than the non-booster seat users (p < 0.01). Continued education and programs surrounding CRS use is critical, particularly for children who should be in booster seats.


Bisferiens peaks in the radial artery pressure wave during patent ductus arteriosus in newborn infants: relationship with ascending aortic flow.
Previously, we found evidence that bisferiens peaks in the radial artery pressure wave in the newborn infant may suggest the presence of a left-to-right shunt through a patent ductus arteriosus (PDA). The purpose of the present study was to analyze the origin of this pulsus bisferiens. Starting from the assumption that the radial artery pressure wave form is similar to the aortic pressure wave form, as described previously, we attempted to explain the bisferiens peaks on the basis of echocardiographically obtained ascending aortic flow. We studied 11 preterm mechanically ventilated infants with a left-to-right shunt through a PDA and 7 without. Aortic volume flow was established echocardiographically, and radial artery blood pressure measurement was performed with a high fidelity cathetermanometer system. Ascending aortic peak flow during PDA was significantly higher in the case of PDA, compared with the case without PDA. An augmented peak flow with an abrupt decline after the high peak in PDA, resulting in a sharp pressure peak with a steep decline after the peak, was thought to explain the first sharp peak of pulsus bisferiens. An abrupt decline of flow after peak flow is thought to be due to the fast runoff of blood through the ductus. According to the pulsatile pressure dynamics theories, which state that pressure wave forms consist of forward and backward wave forms, the second peak of the pulsus bisferiens can be explained by the return of the reflected (backward) wave form when the forward wave form has already considerably decreased. We conclude that the bisferiens peaks found in PDA result from a combination of large stroke volume (augmented first peak) and large runoff (quick decline of the forward wave) before the return of the reflected wave.


High-quality draft genome sequence of Sedimenticola selenatireducens strain AK4OH1T, a gammaproteobacterium isolated from estuarine sediment.
Sedimenticola selenatireducens strain AK4OH1T (= DSM 17993T = ATCC BAA-1233T) is a microaerophilic bacterium isolated from sediment from the Arthur Kill intertidal strait between New Jersey and Staten Island, NY. S. selenatireducens is Gram-negative and belongs to the Gammaproteobacteria. Strain AK4OH1T was the first representative of its genus to be isolated for its unique coupling of the oxidation of aromatic acids to the respiration of selenate. It is a versatile heterotroph and can use a variety of carbon compounds, but can also grow lithoautotrophically under hypoxic and anaerobic conditions. The draft genome comprises 4,588,530 bp and 4276 predicted protein-coding genes including genes for the anaerobic degradation of 4-hydroxybenzoate and benzoate. Here we report the main features of the genome of S. selenatireducens strain AK4OH1T.


Comparative Analysis of Multiplex Platforms for Detecting Vitreous Biomarkers in Diabetic Retinopathy.
To evaluate the feasibility of using the Proximity Extension Assay (PEA) platform to detect biomarkers in vitreous and to compare the findings with results obtained with an electrochemiluminescent (ECL) sandwich immunoassay. Vitreous samples from patients with proliferative diabetic retinopathy (PDR) and non-diabetic controls were tested using two different proteomics platforms. Forty-one assays were completed with the ECL platform and 459 with the PEA platform. Spearman's rank correlation coefficient (rs ) was used to determine the direction and strength of the relationship between protein levels detected by both platforms. Three hundred sixty-six PEA assays detected the tested protein in at least 25% of samples, and the difference in protein abundance between PDR and controls was statistically significant for 262 assays. Seventeen ECL assays yielded a detection rate ≥ 25%, and the difference in protein concentration between PDR and controls was statistically significant for 13 proteins. There was a subset of proteins that were detected by both platforms, and for those the Spearman's correlation coefficient was higher than 0.8. PEA is suitable for the analysis of vitreous samples, showing a strong correlation with the ECL platform. The detection rate of PEA panels was higher than the panels tested with ECL. The levels of several proinflammatory and angiogenic cytokines were significantly higher in PDR vitreous compared to controls. This study provides new information on the yields of small-volume assays that can detect proteins of interest in ocular specimens, and it identifies patterns of cytokine dysregulation in PDR.


Model of gene expression in extreme cold - reference transcriptome for the high-Antarctic cryopelagic notothenioid fish Pagothenia borchgrevinki.
Among the cold-adapted Antarctic notothenioid fishes, the high-latitude bald notothen Pagothenia borchgrevinki is particularly notable as the sole cryopelagic species, exploiting the coldest and iciest waters of the Southern Ocean. Because P. borchgrevinki is a frequent model for investigating notothenioid cold-adaptation and specialization, it is imperative that "omic" tools be developed for this species. In the absence of a sequenced genome, a well annotated reference transcriptome of the bald notothen will serve as a model of gene expression in the coldest and harshest of all polar marine environments, useful for future comparative studies of cold adaptation and thermal responses in polar teleosts and ectotherms. We sequenced and annotated a reference transcriptome for P. borchgrevinki, with added attention to capturing the transcriptional responses to acute and chronic heat exposures. We sequenced by Roche 454 a normalized cDNA library constructed from pooled mRNA encompassing multiple tissues taken from environmental, warm acclimating, and acute heat stressed specimens. The resulting reads were assembled into 42,620 contigs, 17,951 of which could be annotated. We utilized this annotated portion of the reference transcriptome to map short Illumina reads sequenced from the gill and liver of environmental specimens, and also compared the gene expression profiles of these two tissue transcriptomes with those from the temperate model fish Danio rerio. From this, we identified a conserved group of 58 GO terms, in which terms related to transcription and its regulation, ubiquitin-protein ligase activity, protein ubiquitination, and protein binding among others are more prevalent in the bald notothen, suggesting the pertinent genes play essential roles in cold temperature functioning. We sequenced multiple tissue transcriptomes from native and heat-exposed experimental specimens of the high Antarctic, cryopelagic notothenioid P. borchgrevinki to construct a reference transcriptome. In a proof of concept, we utilized the annotated reference transcriptome to profile the gene expression patterns of gill and liver, and identified a suite of over and under-represented GO terms when compared to the tropical water zebrafish suggesting these functions may be important for surviving in freezing waters. The transcriptome resource from this study will aid future investigations of cold adaptation and thermal response of polar ectothermic species.


Delayed endoluminal vacuum therapy for rectal anastomotic leaks after rectal resection in a swine model: a new treatment option.
Anastomotic leaks are a dreaded surgical complication following colorectal operations. Creation of a temporary proximal diverting ileostomy is used in high-risk anastomoses, however, additional surgical risk is accumulated with its creation and reversal. Endoluminal vacuum therapy has been shown to seal anastomotic defects in the prophylactic setting in a pig model and we hypothesized it could be utilized in a delayed fashion to rescue subjects with an active anastomotic leak. Yorkshire pigs underwent rectal resection, intentional leak confirmed by fluoroscopy, and endoluminal vacuum therapy device placement to low continuous suction. Following treatment, a contrast enema and necropsy was performed for gross and histopathology. Pigs underwent 2 (or 5) days of free intraperitoneal leak prior to device placement and 5 (or 7) subsequent days of endoluminal vacuum therapy. Six of seven early-treated pigs sealed their anastomotic defect, while two of the four treated pigs in this extended group sealed the defect. Endoluminal vacuum therapy is feasible and well tolerated in a pig model, and it has been shown to seal a significant number of freely leaking anastomoses in the early period (86%). This technology warrants further study as it may provide a noninvasive means to treatment of anastomotic leaks.


Electrical synapses between AII amacrine cells in the retina: Function and modulation.
Adaptation enables the visual system to operate across a large range of background light intensities. There is evidence that one component of this adaptation is mediated by modulation of gap junctions functioning as electrical synapses, thereby tuning and functionally optimizing specific retinal microcircuits and pathways. The AII amacrine cell is an interneuron found in most mammalian retinas and plays a crucial role for processing visual signals in starlight, twilight and daylight. AII amacrine cells are connected to each other by gap junctions, potentially serving as a substrate for signal averaging and noise reduction, and there is evidence that the strength of electrical coupling is modulated by the level of background light. Whereas there is extensive knowledge concerning the retinal microcircuits that involve the AII amacrine cell, it is less clear which signaling pathways and intracellular transduction mechanisms are involved in modulating the junctional conductance between electrically coupled AII amacrine cells. Here we review the current state of knowledge, with a focus on the recent evidence that suggests that the modulatory control involves activity-dependent changes in the phosphorylation of the gap junction channels between AII amacrine cells, potentially linked to their intracellular Ca(2+) dynamics. This article is part of a Special Issue entitled Electrical Synapses.


Adolescents' religious discordance with mothers: is there a connection to sexual risk behavior during emerging adulthood?
This study longitudinally investigates the relationship between adolescent/mother religious discordance and emerging adult sexual risk-taking 6-7 years later. We used Social Control Theory to examine the level and direction of concordance using data from Wave I and Wave III of the Add Health Study, focusing on constructs of religious importance, frequency of prayer, and attendance at religious services. We found that higher levels of adolescent/mother discordance in religious importance were related to increased emerging adult sexual risk-taking compared to those with similar levels adolescent/mother religiosity, but this occurred only when mothers reported higher levels of religious importance than their children. In contrast, adolescents reporting higher frequency of prayer than their mothers reported lower levels of sexual risk-taking than those with similar frequency of adolescent/mother prayer. These findings suggest that the protective effects of family religious socialization can be interrupted. However, this influence of religious difference on sexual risk-behavior operates differently depending on the direction and level of religious difference. Even in emerging adulthood, a period marked by distance from childhood values and institutions, religious difference with a parent remains a meaningful influence.


Cognitive behavioural therapy for depression and anxiety in adults with acquired brain injury: what works for whom?
This paper reviews treatment outcome studies on cognitive behavioural therapy (CBT) for depression and anxiety following acquired brain injury (ABI), including traumatic brain injury (TBI), cerebral vascular accident (CVA), anoxia and neurosurgery. Studies are included for review when the published paper included an anxiety disorder or depression as the treatment focus, or as part of outcome measurement. Relaxed criteria were used to select studies including relevant single-cases, case series and single group studies along with studies that employed control groups. Twenty-four studies were identified. Twelve papers were of a single-case design (with or without replication). Two papers used uncontrolled single groups and ten studies used a control group. There were a total of 507 people in the various treatment and control groups, which ranged in size from 6 to 67 persons. All participants in the study had an ABI. Our review indicates CBT often shows a within-group pre- to post-treatment statistical difference for depression and anxiety problems, or a statistical difference between CBT-treated and non-treated groups. For studies that targeted the treatment of depression with CBT, effect-sizes ranged from 0 to 2.39 with an average effect-size of 1.15 for depression (large effect). For studies that targeted the treatment of anxiety with CBT, effect-sizes ranged from 0 to 3.47 with an average effect-size of 1.04 for anxiety (large effect). However, it was not possible to submit all twenty-four studies identified to effect-size analysis. Additionally, it is clear that CBT is not a panacea, as studies frequently indicate only partial reduction in anxiety and depression symptoms. This review suggests that if CBT is aimed at, for example, anger management or coping, it can be effective for anger or coping, but will not generalise to have an effect on anxiety or depression. CBT interventions that target anxiety and depression specifically appear to generate better therapeutic effects on anxiety and depression. Gaps in the literature are highlighted with suggestions for future research.


Prenatal alcohol exposure and educational achievement in children aged 8-9 years.
This study examines the relationships between the dose, pattern, and timing of prenatal alcohol exposure and achievement in reading, writing, spelling, and numeracy in children aged 8 to 9 years. Data from a randomly selected, population-based birth cohort of infants born to non-Indigenous women in Western Australia between 1995 and 1997 (n = 4714) (Randomly Ascertained Sample of Children born in Australia's Largest State Study cohort) were linked to the Western Australian Midwives' Notification System and the Western Australian Literacy and Numeracy Assessment statewide education testing program. The records for 86% (n = 4056) of the cohort were successfully linked with education records when the children were aged 8 to 9 years. The associations between prenatal alcohol exposure and achievement of national benchmarks in school numeracy, reading, spelling, and writing tests and nonattendance for the tests was examined. Logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI), adjusting for potential confounding factors. The referent group included children of mothers who previously drank alcohol but who abstained during pregnancy. Children were twice as likely not to achieve the benchmark for reading after heavy prenatal alcohol exposure during the first trimester (aOR 2.26; 95% CI 1.10-4.65) and for writing when exposed to occasional binge drinking in late pregnancy (aOR 2.35; 95% CI 1.04-5.43). Low-moderate prenatal alcohol exposure was not associated with academic underachievement. The type of learning problems expressed depends on the dose, pattern, and timing of prenatal alcohol exposure.


Olive leaf extract concentrated in hydroxytyrosol attenuates protein carbonylation and the formation of advanced glycation end products in a hepatic cell line (HepG2).
Glycation takes place both at the cellular level and at the extracellular matrix level and generates, consequently, advanced glycation end-products (AGEs) associated with chronic diseases and the aging process. Two olive leaf extracts concentrated in (i) oleuropein (OLE-A; 93.9 mg oleuropein g-1) and (ii) hydroxytyrosol (OLE-B; 54.5 mg hydroxytyrosol g-1) were evaluated according to their antiglycative and antioxidant capacity in vitro. OLE-B exerted the highest anti-AGE effect in different glycation models (IC50: 0.25-0.29 mg mL-1). OLE-B showed the highest antioxidant capacity and methylglyoxal-trapping capacity (IC50 0.16 mg mL-1). OLE-B showed a significant inhibitory effect against protein carbonylation (21%) and generation of argpyrimidine (26%) in a hepatocyte cellular carbonyl stress model evoked by methylglyoxal (MGO). OLE-B was further fractionated by solid phase-extraction, and the protective effect against protein carbonylation was only exerted by the fraction containing hydroxytyrosol. However, hydroxytyrosol standard, at the same concentration in the extract, inhibited the protein carbonylation below 10% but not significantly. The results indicate that the antiglycative activity of OLE in cells could be due to a synergic effect of hydroxytyrosol and other minor compounds with similar polarity. The research of the antiglycative activity in vivo could confirm these promising results and to propose OLE as a natural anti-AGE agent.


Effects of messaging on public support for drug consumption rooms in scotland, UK.
There is evidence to suggest that medically supervised drug consumption rooms (DCRs) may form part of responses to reduce drug-related harm. Although DCRs have been established globally, they are perceived by some to be a controversial approach in the UK, and Government has repeatedly rejected proposals to establish one in Glasgow, Scotland. As public support is an important component of policy development and enactment, we sought to investigate the effects of different types of message framing on public support for DCR. We undertook a cross-sectional online study with a randomised design, conducted with a nationally representative sample. Participants were randomised to one of six message conditions comprising combinations of four components. All conditions included i) a basic description of a DCR, and conditions included combinations of ii) factual information; iii) pre-emptive refutation of common public concerns about DCR; and/or iv) a sympathetic narrative describing a mother whose son died from a heroin overdose. After reading each message, participants completed a bespoke measure assessing support for DCR. Data were analysed using ANCOVA. Complete data were obtained from 1591 participants (50.3% Female; mean age 44.9 ± 16.1 years). Compared to reading a basic description of DCR alone, there was greater support for DCR in participants receiving the refutation (p < .001); sympathetic + factual (p < .05); and sympathetic + factual + refutation (p < .001) message conditions. Presenting factual or sympathetic messages alone were not associated with increased support. Our findings suggest that public support for DCRs is not improved through communication of factual statements outlining potential benefits of the intervention alone. Advocates seeking to foster public support, and thus influence policy making, should also consider communication campaigns that address common concerns that the public might have about DCRs, and present the intervention in relation to potential benefits that they hold for people indirectly affected by drug-related harm.


[Malaria control in Brazil: 1965 to 2001].
This paper reviews malaria control initiatives in Brazil, from the Malaria Eradication Campaign (Campanha de Erradicação da Malária), which was launched in 1965 and was based on spraying dichlorodiphenyltrichloroethane (DDT) and on administering antimalarial drugs, to the implementation, in 2000, of the Program for Intensification of Malaria Control in the nine-state Legal Amazon region of Brazil (Plano de Intensificação das Ações de Controle da Malária na Amazônia Legal), which was implemented in response to the World Health Organization's Roll Back Malaria effort. Among the Brazilian initiatives discussed are epidemiological stratification, the Impact Operation (Operação Impacto), the Amazon Basin Malaria Control Project (Projeto de Controle da Malária na Bacia Amazônica), and the Integrated Malaria Control Program (Programa de Controle Integrado da Malária). Although there was progress in the control of malaria before the Intensification Program was launched in 2000, the actions carried out were not sustained. From 1998 to 1999 there was even a 34% increase in the number of malaria cases in the Brazilian Amazon. The Intensification Program set a goal, in comparison to 1999, of reducing by 50% the number of malaria cases by the end of 2001 and of cutting by 50% the mortality due to malaria by the end of 2002. Data for 2001 showed an overall 39% decrease in the number of malaria cases in the nine Amazonian states of the Intensification Program. The smallest decrease (15%) was in the state of Amapá, where the plan was not implemented until the second half of 2001. In terms of incidence by species, there was a 35% reduction in cases caused by Plasmodium falciparum and a 41% reduction in cases caused by P. vivax. The only independent variable that explains this reduction is the implementation of the Intensification Program. Although preliminary, these results indicate considerable gains. Decisive to this progress has been the strong mobilization of federal, state, and municipal governments.


Health in All Policies in South Australia: what has supported early implementation?
Health in All Policies (HiAP) is a policy development approach that facilitates intersectoral responses to addressing the social determinants of health and health equity whilst, at the same time, contributing to policy priorities across the various sectors of government. Given that different models of HiAP have been implemented in at least 16 countries, there is increasing interest in how its effectiveness can be optimized. Much of the existing literature on HiAP remains descriptive, however, and lacks critical, empirically informed analyses of the elements that support implementation. Furthermore, literature on HiAP, and intersectoral action more generally, provides little detail on the practical workings of policy collaborations. This paper contributes empirical findings from a multi-method study of HiAP implementation in South Australia (SA) between 2007 and 2013. It considers the views of public servants and presents analysis of elements that have supported, and impeded, implementation of HiAP in SA. We found that HiAP has been implemented in SA using a combination of interrelated elements. The operation of these elements has provided a strong foundation, which suggests the potential for HiAP to extend beyond being an isolated strategy, to form a more integrated and systemic mechanism of policy-making. We conclude with learnings from the SA experience of HiAP implementation to inform the ongoing development and implementation of HiAP in SA and internationally.


Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite.
As peroxynitrite is implicated as an oxidant for low-density lipoprotein (LDL) in atherogenesis, we investigated this process using reagent peroxynitrite (ONOO-) and 3-morpholinosydnonimine (SIN-1, which produces peroxynitrite via generation of NO. and O2.-). LDL oxidation was assessed by the consumption of ubiquinol-10 (CoQ10H2) and alpha-tocopherol (alpha-TOH), the accumulation of cholesteryl ester hydro(pero)xides, the loss of lysine (Lys) and tryptophan (Trp) residues, and the change in relative electrophoretic mobility. Exposure to ONOO- or SIN-1 resulted in rapid (<1 min) and time-dependent oxidation, respectively, of LDL's lipids and protein. Manipulating the alpha-TOH content by in vivo or in vitro means showed that when ONOO- or SIN-1 was used at oxidant-to-LDL ratios of <100:1 the extent of LDL lipid peroxidation increased with increasing initial alpha-TOH content. In contrast, in vivo enrichment with the co-antioxidant CoQ10H2 decreased LDL lipid peroxidation induced by SIN-1. At oxidant-to-LDL ratios of >200:1, alpha-TOH enrichment decreased LDL lipid peroxidation for both SIN-1 and ONOO-. In contrast to lipid peroxidation, altering the alpha-TOH content of LDL did not affect Trp or Lys loss, independent of the amounts of either oxidant added. Aqueous antioxidants inhibited ONOO--induced lipid and protein oxidation with the order of efficacy: 3-hydroxyanthranilate (3-HAA) > urate > ascorbate. With SIN-1, these antioxidants inhibited Trp consumption, while only the co-antioxidants ascorbate and 3-HAA prevented alpha-TOH consumption and lipid peroxidation. Exposure of human plasma to SIN-1 resulted in the loss of ascorbate followed by loss of CoQ10H2 and bilirubin. Lipid peroxidation was inhibited during this period, though proceeded as a radical-chain process after depletion of these antioxidants and in the presence of alpha-TOH and urate. Bicarbonate at physiological concentrations decreased ONOO--induced lipid and protein oxidation, whereas it enhanced SIN-1-induced lipid peroxidation, Trp consumption, and alpha-tocopheroxyl radical formation in LDL. These results indicate an important role for tocopherol-mediated peroxidation and co-antioxidation in peroxynitrite-induced lipoprotein lipid peroxidation, especially when peroxynitrite is formed time-dependently by SIN-1. The studies also highlight differences between ONOO-- and SIN-1-induced LDL oxidation with regards to the effects of bicarbonate, ascorbate, and urate.


HEF1 is a crucial mediator of the proliferative effects of prostaglandin E(2) on colon cancer cells.
Prostaglandin E(2) (PGE(2)), one of the downstream products of cyclooxygenase-2 enzymatic activity, promotes colorectal carcinogenesis in part by stimulating cell division. In this study, we define a critical mechanism in this process by showing that the prometastatic adapter protein human enhancer of filamentation 1 (HEF1; NEDD9) links PGE(2) to the cell cycle machinery in colorectal cancer cells. PGE(2) rapidly induced expression of HEF1 mRNA and protein in colorectal cancer cells. HEF1 overexpression elicited the same effects as PGE(2) treatment on cell proliferation, cell cycle progression, and tumor growth. Conversely, HEF1 knockdown suppressed PGE(2)-driven cell proliferation and cell cycle progression. Cell cycle alterations involved HEF1 fragmentation as well as co-distribution of HEF1 and cell cycle kinase Aurora A along spindle asters during cell division. Moreover, Aurora A co-immunoprecipitated with HEF1 and was activated by HEF1. Consistent with a role for HEF1 in colorectal carcinogenesis, we found elevated expression of HEF1 expression in 50% of human colorectal cancers examined, relative to paired normal tissues. These findings establish that PGE(2) induces HEF1 expression, which in turn promotes cell cycle progression through its interaction with and activation of Aurora A. Further, they establish that HEF1 is a crucial downstream mediator of PGE(2) action during colorectal carcinogenesis.


Sustaining the Clinical and Translational Research Workforce: Training and Empowering the Next Generation of Investigators.
There is mounting concern that clinician-scientists are a vanishing species and that the pipeline for clinical and translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH)-funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional "culture shift" are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical and Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the time frame, increasing the rate of K2R transition, and identifying strategies that improve success.


Fasting serum apolipoprotein B-48 can be a marker of postprandial hyperlipidemia.
Postprandial hyperlipidemia (PH) is thought to be caused by the impaired postprandial metabolism of triglycerides (TG)-rich lipoproteins in both endogenous and exogenous pathways; however, there is no consensus. It is difficult to estimate the presence of PH without performing a time-consuming oral fat loading (OFL) test, so postprandial lipoprotein metabolism was analyzed by measuring the postprandial levels of apolipoprotein (apo) B-48 and apo B-100, and the correlation between postprandial TG increase and fasting apoB-48 levels was assessed to establish a good marker of PH without performing an OFL test. Ten male normolipidemic subjects were loaded with a high-fat (HF, 1045 kcal) or standard (ST, 566 kcal) meal, and the lipids, apolipoproteins and lipoprotein profiles were analyzed after each meal. TG, apo B-48, remnant-like particles (RLP)-cholesterol and RLP-TG levels were increased and their levels were significantly higher after intake of the HF meal than the ST meal; however, there was no postprandial increase in apo B-100 and LDL-C levels. Postprandial increases in TG levels of CM, VLDL, LDL and HDL were significantly higher after intake of the HF meal than the ST meal. Fasting apo B-48 levels were strongly correlated with the incremental area under the curve of TG after intake of the HF meal, but not the ST meal. Postprandial TG increase was mainly due to increased CM and CM-R, but not VLDL. Measurement of fasting serum apo B-48 may be a simple and useful method for assessment of the existence of PH.


Induction of transcription from the long terminal repeat of Moloney murine sarcoma provirus by UV-irradiation, x-irradiation, and phorbol ester.
The long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MuSV) was used as a model system to study the stress response of mammalian cells to physical carcinogens. The chloramphenicol acetyltransferase (CAT) gene was inserted between two Mo-MuSV LTRs, and the LTR-CAT-LTR construct was used for virus production and was integrated into the genome of NIH 3T3 cells in the proviral form. This construct was used to assure that the integrated CAT gene was driven by the promoter of the LTR. Expression of the CAT gene was stimulated 4-fold by UV irradiation, and the peak of activity was observed at 18 hr. In contrast, stimulation of the CAT expression after x-irradiation was 2-fold and occurred at 6 hr. Phorbol myristate acetate also stimulated CAT activity 4-fold with a peak at 6 hr. Down-regulation of protein kinase C blocked totally the response to x-irradiation but only partially the response to UV. The protein kinase inhibitor H7 blocked the response to treatment by UV, x-ray, and phorbol ester.


Infection of Onion Leaves by Pantoea ananatis Leads to Bulb Infection.
Pantoea ananatis has been identified as a cause of center rot of onion. In the field, onion leaves can become infected with P. ananatis and lead to leaf blight. Infected bulbs often are detected only after harvest; however, it has not been demonstrated experimentally that leaf infection by P. ananatis can lead to bulb infection. In this study, onion leaf infection by P. ananatis leading to bulb infection was investigated. Of 18 strains of P. ananatis isolated from symptomatic onion bulbs grown in New York, 14 were pathogenic in bulb and leaf tissue. Pathogenic strains of P. ananatis caused nonmacerated, yellow-brown coloration in fleshy bulb scales following inoculation of bulbs and incubation for 2 days at 28°C. Subepidermal inoculation of onion leaves with pathogenic strains of P. ananatis resulted in gray-white foliar lesions that extended acropetally and basipetally from the points of inoculation. In all, 16% of leaf lesions extended to the onion neck and 11% continued into the bulbs, which developed nonmacerated, yellow-brown scales. Bacteria recovered from the leading edges of lesions had microbiological and molecular characteristics of P. ananatis. This is the first experimental evidence that infection of onion leaves by P. ananatis can lead to bulb infection.


Disrupting intergenerational continuity in harsh and abusive parenting: the importance of a nurturing relationship with a romantic partner.
Harsh, abusive, and rejecting behavior by parents toward their children is associated with increased risk for many developmental problems for youth. Earlier research also shows that children raised by harsh parents are more likely to treat their own children harshly. The present study evaluated nurturing and supportive behaviors of spouses or cohabiting romantic partners hypothesized to strengthen co-parent relationships and help break this intergenerational cycle of harsh parenting. Data come from the Family Transitions Project, a 22-year, 3-generation study of a cohort of over 500 early adolescents (G2) grown to adulthood. During adolescence, observers rated G1 (parent of G2) harsh parenting to G2. Several years later, observers rated G2 harsh parenting toward their oldest child (G3). In addition, G2's romantic partner (spouse or cohabiting partner) was rated by observers on a range of behaviors expected to affect G2 harsh parenting. Romantic partner warmth and positive communication with G2 were associated with less G2 harsh parenting toward G3 (a compensatory or main effect) and when these partner behaviors were high, there was no evidence of intergenerational continuity from G1 to G2 harsh parenting (a moderating or protective effect). G1 harsh parenting slightly decreased the likelihood that G2 would select a supportive spouse or romantic partner (evidence of cumulative continuity). Romantic partner warmth and positive communication appear to disrupt continuity in harsh and abusive parenting. As appropriate, preventive interventions designed to reduce risk for child maltreatment should include a focus on spousal or partner behaviors in their educational or treatment programs.


TCR sequencing of single cells reactive to DQ2.5-glia-α2 and DQ2.5-glia-ω2 reveals clonal expansion and epitope-specific V-gene usage.
CD4+ T cells recognizing dietary gluten epitopes in the context of disease-associated human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 molecules are the key players in celiac disease pathogenesis. Here, we conducted a large-scale single-cell paired T-cell receptor (TCR) sequencing study to characterize the TCR repertoire for two homologous immunodominant gluten epitopes, DQ2.5-glia-α2 and DQ2.5-glia-ω2, in blood of celiac disease patients after oral gluten challenge. Despite sequence similarity of the epitopes, the TCR repertoires are unique but shared several overall features. We demonstrate that clonally expanded T cells dominate the T-cell responses to both epitopes. Moreover, we find V-gene bias of TRAV26, TRAV4, and TRBV7 in DQ2.5-glia-α2 reactive TCRs, while DQ2.5-glia-ω2 TCRs displayed significant bias toward TRAV4 and TRBV4. The knowledge that antigen-specific TCR repertoire in chronic inflammatory diseases tends to be dominated by a few expanded clones that use the same TCR V-gene segments across patients is important information for HLA-associated diseases where the antigen is unknown.


Steady-state analysis of activated sludge processes with a settler model including sludge compression.
A reduced model of a completely stirred-tank bioreactor coupled to a settling tank with recycle is analyzed in its steady states. In the reactor, the concentrations of one dominant particulate biomass and one soluble substrate component are modelled. While the biomass decay rate is assumed to be constant, growth kinetics can depend on both substrate and biomass concentrations, and optionally model substrate inhibition. Compressive and hindered settling phenomena are included using the Bürger-Diehl settler model, which consists of a partial differential equation. Steady-state solutions of this partial differential equation are obtained from an ordinary differential equation, making steady-state analysis of the entire plant difficult. A key result showing that the ordinary differential equation can be replaced with an approximate algebraic equation simplifies model analysis. This algebraic equation takes the location of the sludge-blanket during normal operation into account, allowing for the limiting flux capacity caused by compressive settling to easily be included in the steady-state mass balance equations for the entire plant system. This novel approach grants the possibility of more realistic solutions than other previously published reduced models, comprised of yet simpler settler assumptions. The steady-state concentrations, solids residence time, and the wastage flow ratio are functions of the recycle ratio. Solutions are shown for various growth kinetics; with different values of biomass decay rate, influent volumetric flow, and substrate concentration.


Neutrophil elastase triggers the development of autoimmune diabetes by exacerbating innate immune responses in pancreatic islets of non-obese diabetic mice.
Type 1 diabetes is an autoimmune disease resulted from self-destruction of insulin-producing pancreatic β cells. However, the pathological pathways that trigger the autoimmune destruction remain poorly understood. Clinical studies have demonstrated close associations of neutrophils and neutrophil elastase (NE) with β-cell autoimmunity in patients with Type 1 diabetes. The present study aims to investigate the impact of NE inhibition on development of autoimmune diabetes in NOD mice. NE pharmacological inhibitor (sivelestat) or biological inhibitor (elafin) was supplemented into NOD mice to evaluate their effects on islet inflammation and diabetogenesis. The impact of NE inhibition on innate and adaptive immune cells was measured with flow cytometry and immunohistochemistry. A significant but transient increase in neutrophil infiltration accompanied with elevated NE activity was observed in the neonatal period of NOD mice. Treatment of NOD mice with sivelestat or elafin at the early age led to a marked reduction in spontaneous development of insulitis and autoimmune diabetes. Mechanistically, inhibition of NE significantly attenuated infiltration of macrophages and islet inflammation, thus ameliorating cytotoxic T cell-mediated autoimmune attack of pancreatic β cells. In vitro studies showed that NE directly induced inflammatory responses in both min6 β cells and RAW264.7 macrophages, and promoted macrophage migration. These findings support an important role of NE in triggering the onset and progression of β-cell autoimmunity, and suggest that pharmacological inhibition of NE may represent a promising therapeutic strategy for treatment of autoimmune diabetes.


Psychopathic traits moderate peer influence on adolescent delinquency.
Peer influence on adolescent delinquency is well established, but little is known about moderators of peer influence. In this study, we examined adolescents' (targets) and their peers' psychopathic personality traits as moderators of peer influence on delinquency in peer networks. We used three separate dimensions of the psychopathic personality: grandiose-manipulative traits, callous-unemotional traits, and impulsive-irresponsible traits. We used a peer network approach with five waves of longitudinal data from 847 adolescents in one community. Peer nominations were not limited to the school context, thus allowing us to capture all potentially important peers. In addition, peers reported on their own delinquency, thus allowing us to avoid problems of false consensus or projection that arise when individuals report on their peers' delinquency. We used simulation investigation for empirical network analyses (SIENA), which is the only program currently available that can be used to study peer influence effects in peer networks of multiple relationships while controlling for selection effects. Targets' and peers' callous-unemotional and grandiose-manipulative traits uniquely moderated peer influence on delinquency. Relative to those with low levels, targets who were high on these traits were less influenced by peers' delinquency, and peers who were high on these traits were more influential on targets' delinquency. Selection effects were found for impulsive-irresponsible traits, but these traits did not moderate peer influence on delinquency. As the first study to look at moderating effects of psychopathic traits on peer influence, this study advances knowledge about peer influence on delinquency and about psychopathic traits in adolescents. In addition, the study contributes to the literature by looking at unique effects of the three dimensions of psychopathy and taking a peer network approach, in which network effects, self-selection, and other selection effects are controlled when examining influence and moderators of influence.


The effectiveness of a primary care nursing-led dietary intervention for prediabetes: a mixed methods pilot study.
Primary care nurse-led prediabetes interventions are seldom reported. We examined the implementation and feasibility of a 6-month multilevel primary care nurse-led prediabetes lifestyle intervention compared with current practice in patients with prediabetes, with weight and glycated haemoglobin (HbA1c) as outcomes. This study used a convergent mixed methods design involving a 6-month pragmatic non-randomised pilot study with a qualitative process evaluation, and was conducted in two neighbouring provincial cities in New Zealand, with indigenous Māori populations comprising 18.2% and 23.0%, respectively. Participants were non-pregnant adults aged ≤ 70 years with newly diagnosed prediabetes (HbA1c 41-49 mmol/mol), body mass index (BMI) ≥ 25 kg/m2 and not prescribed Metformin. A structured dietary intervention tool delivered by primary care nurses with visits at baseline, 2-3 weeks, 3 months and 6 months was implemented in four intervention practices. Four control practices continued to provide usual care. Primary quantitative outcome measures were weight and HbA1c. Linear and quantile regression models were used to compare each outcome between the two groups at follow-up. Qualitative data included: observations of nurse training sessions and steering group meetings; document review; semi-structured interviews with a purposive sample of key informants (n = 17) and intervention patients (n = 20). Thematic analysis was used. One hundred fifty-seven patients with prediabetes enrolled (85 intervention, 72 control), 47.8% female and 31.2% Māori. Co-morbidities were common, particularly hypertension (49.7%), dyslipidaemia (40.1%) and gout (15.9%). Baseline and 6 month measures were available for 91% control and 79% intervention participants. After adjustment, the intervention group lost a mean 1.3 kg more than the control group (p < 0.001). Mean HbA1c, BMI and waist circumference decreased in the intervention group and increased in the control group, but differences were not statistically significant. Implementation fidelity was high, and it was feasible to implement the intervention in busy general practice settings. The intervention was highly acceptable to both patients and key stakeholders, especially primary care nurses. Study findings confirm the feasibility and acceptability of primary care nurses providing structured dietary advice to patients with prediabetes in busy general practice settings. The small but potentially beneficial mean weight loss among the intervention group supports further investigation. ANZCTR ACTRN12615000806561 . Registered 3 August 2015 (Retrospectively registered).


Changing single side-chains can greatly enhance the resistance of a membrane protein to irreversible inactivation.
The thermal inactivation rates of a set of 20 cysteine-substituted variants of the integral membrane protein diacylglycerol kinase were measured. Two of the mutations, I53C and I70C, were found to significantly prolong the half-life of the enzyme in detergent solution. By combining the single mutants to create a double mutant, I53C/I70C, the half-life of the enzyme was improved from less than a minute at 70 degrees C to 51 minutes. These results demonstrate that individual side-chain substitutions can significantly improve the properties of membrane proteins in detergent solution.


The relative contributions of facial shape and surface information to perceptions of attractiveness and dominance.
Although many studies have investigated the facial characteristics that influence perceptions of others' attractiveness and dominance, the majority of these studies have focused on either the effects of shape information or surface information alone. Consequently, the relative contributions of facial shape and surface characteristics to attractiveness and dominance perceptions are unclear. To address this issue, we investigated the relationships between ratings of original versions of faces and ratings of versions in which either surface information had been standardized (i.e., shape-only versions) or shape information had been standardized (i.e., surface-only versions). For attractiveness and dominance judgments of both male and female faces, ratings of shape-only and surface-only versions independently predicted ratings of the original versions of faces. The correlations between ratings of original and shape-only versions and between ratings of original and surface-only versions differed only in two instances. For male attractiveness, ratings of original versions were more strongly related to ratings of surface-only than shape-only versions, suggesting that surface information is particularly important for men's facial attractiveness. The opposite was true for female physical dominance, suggesting that shape information is particularly important for women's facial physical dominance. In summary, our results indicate that both facial shape and surface information contribute to judgments of others' attractiveness and dominance, suggesting that it may be important to consider both sources of information in research on these topics.


A comparative perspective on intermarriage: explaining differences among national-origin groups in the United States.
Little is known about the validity of group-level theories of ethnic intermarriage despite the fact that such theories are often invoked in explaining why certain ethnic groups are "closed," whereas others are relatively "open." We develop a comparative perspective by analyzing the marriage choices of 94 national-origin groups in the United States, using pooled data from the Current Population Surveys, 1994-2006, and multilevel models in which individual and contextual determinants of intermarriage are included simultaneously. Our analyses show large differences in endogamy across groups. After taking compositional effects into account, we find that both structural and cultural group-level factors have significant effects on endogamy. Cultural explanations (which focus on the role of norms and preferences) play a more important role than structural explanations (which focus on meeting and mating opportunities). Our results reinforce the common but untested interpretation of endogamy in terms of group boundaries.


FIM$^{2c\;}$: Multicolor, Multipurpose Imaging System to Manipulate and Analyze Animal Behavior.
In vivo whole-body imaging of small animals plays an important role for biomedical studies. In particular, animals like the fruit fly Drosophila melanogaster or the nematode Caenorhabditis elegans are popular model organisms for preclinical research since they offer sophisticated genetic tool-kits. Recording these translucent animals with high contrast in a large arena is however not trivial. Furthermore, fluorescent proteins are widely used to mark cells in vivo and report their functions. This paper introduces a novel optical imaging technique called FIM2c enabling simultaneous detection of the animals posture and movement as well as fluorescent markers like green fluorescent protein (GFP). FIM2c utilizes frustrated total internal reflection of two distinct wavelengths and captures both, reflected and emitted light. The resultant two-color high-contrast images are superb compared to other imaging systems for larvae or worms. This multipurpose method enables a large variety of different experimental approaches. For example, FIM2c can be used to image GFP positive cells/tissues/animals and supports the integration of fluorescent tracers into multitarget tracking paradigms. Moreover, optogenetic tools can be applied in large-scale behavioral analysis to manipulate and study neuronal functions. To demonstrate the benefit of our system, we use FIM2c to resolve colliding larvae in a high-throughput approach, which was impossible given the existing tools. Finally, we present a comprehensive database including images and locomotion features of more than 1300 resolved collisions available for the community. In conclusion, FIM2c is a versatile tool for advanced imaging and locomotion analysis for a variety of different model organisms.


Renal Na/Pi-cotransporters.
Two non-homologous proximal tubular apical Na/Pi-cotransport systems (type I and type II) have been identified thus far by expression cloning. Subsequent studies provided evidence that the type II Na/Pi-cotransporter represents a target for the physiological and pathophysiological regulation of proximal reabsorption of phosphate. The exact role of the type I Na/Pi-cotransporter in proximal Pi-reabsorption and eventually also in the renal handling of other substrates, such as organic anions, is currently less clear and needs further investigation. Evidence was obtained that acute changes of brush border membrane Na/Pi-cotransport involves endo- and exocytic movement of type II Na/Pi-cotransporters. In particular, we elucidated if and how phosphorylation reactions are involved and defined the intracellular structures of the endo/exocytic apparatus involved. At the level of the gene it will be necessary to elucidate its organization in order to understand the mechanisms involved in chronic regulations of Na/Pi-cotransport related to the type II Na/Pi-cotransporter. Furthermore, for structural investigations of these integral membrane proteins, they have to be isolated in sufficient quantities. Thus far the type II cotransporter (NaPi-2) has been expressed in Sf9 insect cells [20], which may eventually allow a purification of this protein.


Bariatric surgery: an evidence-based analysis.
To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of bariatric surgery. Obesity is defined as a body mass index (BMI) of at last 30 kg/m(2).() Morbid obesity is defined as a BMI of at least 40 kg/m(2) or at least 35 kg/m(2) with comorbid conditions. Comorbid conditions associated with obesity include diabetes, hypertension, dyslipidemias, obstructive sleep apnea, weight-related arthropathies, and stress urinary incontinence. It is also associated with depression, and cancers of the breast, uterus, prostate, and colon, and is an independent risk factor for cardiovascular disease. Obesity is also associated with higher all-cause mortality at any age, even after adjusting for potential confounding factors like smoking. A person with a BMI of 30 kg/m(2) has about a 50% higher risk of dying than does someone with a healthy BMI. The risk more than doubles at a BMI of 35 kg/m(2). An expert estimated that about 160,000 people are morbidly obese in Ontario. In the United States, the prevalence of morbid obesity is 4.7% (1999-2000). In Ontario, the 2004 Chief Medical Officer of Health Report said that in 2003, almost one-half of Ontario adults were overweight (BMI 25-29.9 kg/m(2)) or obese (BMI ≥ 30 kg/m(2)). About 57% of Ontario men and 42% of Ontario women were overweight or obese. The proportion of the population that was overweight or obese increased gradually from 44% in 1990 to 49% in 2000, and it appears to have stabilized at 49% in 2003. The report also noted that the tendency to be overweight and obese increases with age up to 64 years. BMI should be used cautiously for people aged 65 years and older, because the "normal" range may begin at slightly above 18.5 kg/m(2) and extend into the "overweight" range. The Chief Medical Officer of Health cautioned that these data may underestimate the true extent of the problem, because they were based on self reports, and people tend to over-report their height and under-report their weight. The actual number of Ontario adults who are overweight or obese may be higher. Diet, exercise, and behavioural therapy are used to help people lose weight. The goals of behavioural therapy are to identify, monitor, and alter behaviour that does not help weight loss. Techniques include self-monitoring of eating habits and physical activity, stress management, stimulus control, problem solving, cognitive restructuring, contingency management, and identifying and using social support. Relapse, when people resume old, unhealthy behaviour and then regain the weight, can be problematic. Drugs (including gastrointestinal lipase inhibitors, serotonin norepinephrine reuptake inhibitors, and appetite suppressants) may be used if behavioural interventions fail. However, estimates of efficacy may be confounded by high rates of noncompliance, in part owing to the side effects of the drugs. In addition, the drugs have not been approved for indefinite use, despite the chronic nature of obesity. Morbidly obese people may be eligible for bariatric surgery. Bariatric surgery for morbid obesity is considered an intervention of last resort for patients who have attempted first-line forms of medical management, such as diet, increased physical activity, behavioural modification, and drugs. There are various bariatric surgical procedures and several different variations for each of these procedures. The surgical interventions can be divided into 2 general types: malabsorptive (bypassing parts of the gastrointestinal tract to limit the absorption of food), and restrictive (decreasing the size of the stomach so that the patient is satiated with less food). All of these may be performed as either open surgery or laparoscopically. An example of a malabsorptive technique is Roux-en-Y gastric bypass (RYGB). Examples of restrictive techniques are vertical banded gastroplasty (VBG) and adjustable gastric banding (AGB). The Ontario Health Insurance Plan (OHIP) Schedule of Benefits for Physician Services includes fee code "S120 gastric bypass or partition, for morbid obesity" as an insured service. The term gastric bypass is a general term that encompasses a variety of surgical methods, all of which involve reconfiguring the digestive system. The term gastric bypass does not include AGB. The number of gastric bypass procedures funded and done in Ontario, and funded as actual out-of-country approvals,() is shown below. Number of Gastric Bypass Procedures by Fiscal Year: Ontario and Actual Out-of-Country (OOC) ApprovalsData from Provider Services, MOHLTCCourtesy of Provider Services, Ministry of Health and Long Term Care The Medical Advisory Secretariat reviewed the literature to assess the effectiveness, safety, and cost-effectiveness of bariatric surgery to treat morbid obesity. It used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. The interventions of interest were bariatric surgery and, for the controls, either optimal conventional management or another type of bariatric procedure. The outcomes of interest were improvement in comorbid conditions (e.g., diabetes, hypertension); short- and long-term weight loss; quality of life; adverse effects; and economic analysis data. The databases yielded 15 international health technology assessments or systematic reviews on bariatric surgery. Subsequently, the Medical Advisory Secretariat searched MEDLINE and EMBASE from April 2004 to December 2004, after the search cut-off date of April, 2004, for the most recent systematic reviews on bariatric surgery. Ten studies met the inclusion criteria. One of those 10 was the Swedish Obese Subjects study, which started as a registry and intervention study, and then published findings on people who had been enrolled for at least 2 years or at least 10 years. In addition to the literature review of economic analysis data, the Medical Advisory Secretariat also did an Ontario-based economic analysis. Bariatric surgery generally is effective for sustained weight loss of about 16% for people with BMIs of at least 40 kg/m(2) or at least 35 kg/m(2) with comorbid conditions (including diabetes, high lipid levels, and hypertension). It also is effective at resolving the associated comorbid conditions. This conclusion is largely based on level 3a evidence from the prospectively designed Swedish Obese Subjects study, which recently published 10-year outcomes for patients who had bariatric surgery compared with patients who received nonsurgical treatment. (1)Regarding specific procedures, there is evidence that malabsorptive techniques are better than other banding techniques for weight loss and resolution of comorbid illnesses. However, there are no published prospective, long-term, direct comparisons of these techniques available.Surgery for morbid obesity is considered an intervention of last resort for patients who have attempted first-line forms of medical management, such as diet, increased physical activity, behavioural modification, and drugs. In the absence of direct comparisons of active nonsurgical intervention via caloric restriction with bariatric techniques, the following observations are made:A recent systematic review examining the efficacy of major commercial and organized self-help weight loss programs in the United States concluded that the evidence to support the use of such programs was suboptimal, except for one trial on Weight Watchers. Furthermore, the programs were associated with high costs, attrition rates, and probability of regaining at least 50% of the lost weight in 1 to 2 years. (2)A recent randomized controlled trial reported 1-year outcomes comparing weight loss and metabolic changes in severely obese patients assigned to either a low-carbohydrate diet or a conventional weight loss diet. At 1 year, weight loss was similar for patients in each group (mean, 2-5 kg). There was a favourable effect on triglyceride levels and glycemic control in the low-carbohydrate diet group. (3)A decision-analysis model showed bariatric surgery results in increased life expectancy in morbidly obese patients when compared to diet and exercise. (4)A cost-effectiveness model showed bariatric surgery is cost-effective relative to nonsurgical management. (5)Extrapolating from 2003 data from the United States, Ontario would likely need to do 3,500 bariatric surgeries per year. It currently does 508 per year, including out-of-country surgeries.


Rocky Mountain spotted fever complicated by gangrene: report of six cases and review.
Although mortality due to fulminant Rocky Mountain spotted fever (RMSF) is well appreciated, the ability of the disease to cause survivors to become permanently disabled is not as widely known. We report six cases of RMSF complicated by gangrene. Although four patients required multiple limb and/or digital amputations, only one death resulted. Our review of the English-language literature revealed 23 additional cases of RMSF complicated by gangrene. Pathophysiologically, gangrene is most likely related to small-vessel occlusion. Skin necrosis and gangrene in association with RMSF are the extreme end on a continuum from reversible to irreversible skin and tissue damage caused by Rickettsia rickettsii. Most patients with RMSF have a typical skin rash that resolves without sequelae. Some patients develop minute cicatrices marking the location of focal cutaneous necrosis; for other patients, digital ischemia occurs transiently or evolves to produce severe ischemic changes without gangrene that result in permanent impairment. At the far end of this clinical continuum are patients who develop gangrene requiring amputation.


Lasing action and optical amplification in Nd3+ doped electrooptic lanthanum lead zirconate titanate ceramics.
Both single-pass gain and lasing action at 1064.4 nm were observed in ceramic gain media of neodymium doped lanthanum-modified lead zirconate titanate, which exhibits good electrooptic (EO) effect from visible through mid-wave IR band (400 nm to 5.5 µm). These works have removed roadblocks off the way leading to development of long envisioned multifunctional optical devices. The impact of the Nd3+ doping concentration on the EO effect in the Nd3+:PLZT ceramics was studied. The finding of the slowly trailing-off was satisfactorily explained with the rich vacancy-based carrier traps, which are responsible for the long persistent optoenergy storage.


Striatal stimulation nurtures endogenous neurogenesis and angiogenesis in chronic-phase ischemic stroke rats.
Deep brain stimulation (DBS) is used to treat a variety of neurological disorders including Parkinson's disease. In this study, we explored the effects of striatal stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation electrode was implanted into the ischemic penumbra at 1 month after middle cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre- and post-SS. The rats with SS showed significant behavioral recovery in the spontaneous activity and limb placement test compared to those without SS. MRI visualized that SS also significantly reduced the infarct volumes compared to that at pre-SS or without SS. Immunohistochemical analyses revealed a robust neurogenic response in rats that received SS characterized by a stream of proliferating cells from the subventricular zone migrating to and subsequently differentiating into neurons in the ischemic penumbra, which exhibited a significant GDNF upregulation. In tandem with this SS-mediated neurogenesis, enhanced angiogenesis was also recognized as revealed by a significant increase in VEGF levels in the penumbra. These results provide evidence that SS affords neurorestoration at the chronic phase of stroke by stimulating endogenous neurogenesis and angiogenesis.


Low nutrient intake among adult women and patients with severe tuberculosis disease in Uganda: a cross-sectional study.
Information regarding dietary nutrient intake during tuberculosis disease is lacking. We established the relationship between disease severity or wasting during pulmonary tuberculosis and nutrient intake. In a cross-sectional study of 131 adults with or without pulmonary tuberculosis were screened for human immune-deficiency virus (HIV), wasting, disease severity using 13 item validated clinical TBscore, and 24-hour dietary intake recall. Of the 131 participants, 61 were males and 70 females. Overall men and women had similar age. In average 24-hour nutrient intake, the following nutrients: energy, protein, total fat, carbohydrate, calcium, vitamin A, and folate were low among patients with severe tuberculosis disease. Patients with moderate-to-severe clinical TBscore had lower average energy intake than patients with mild TBscores (6.11 vs. 9.27 MJ, respectively) (p<0.05). The average 24-hour nutrient intakes between wasted and non-wasted tuberculosis patients were comparable. Nutrient intake among men was higher when compared to women regardless of wasting and severity of tuberculosis. Among those with wasting, men had higher average energy intake than women (8.87 vs. 5.81 MJ, respectively) (p<0.05). Among patients with mild disease, men had higher average energy intake than women with mild disease (12.83 vs. 7.49 kcal, respectively) (p<0.001). Findings suggest that severity of pulmonary tuberculosis and female gender had reduced nutrient intake. Early tuberculosis diagnosis and nutritional support may be important in management of tuberculosis patients.


The structures of Salmonella typhimurium LT2 neuraminidase and its complexes with three inhibitors at high resolution.
The structure of Salmonella typhimurium LT2 neuraminidase (STNA) is reported here to a resolution of 1.6 angstroms together with the structures of three complexes of STNA with different inhibitors. The first is 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid (Neu5Ac2en or DANA), the second and third are phosphonate derivatives of N-acetyl-neuraminic acid (NANA) which have phosphonate groups at the C2 position equatorial (ePANA) and axial (aPANA) to the plane of the sugar ring. The complex structures are at resolutions of 1.6 angstroms, 1.6 angstroms and 1.9 angstroms, respectively. These analyses show the STNA active site to be topologically inflexible and the interactions to be dominated by the arginine triad, with the pyranose rings of the inhibitors undergoing distortion to occupy the space available. Solvent structure differs only around the third phosphonate oxygen, which attracts a potassium ion. The STNA structure is topologically identical to the previously reported influenza virus neuraminidase structures, although very different in detail; the root-mean-square (r.m.s) deviation for 210 C alpha positions considered equivalent is 2.28 angstroms (out of a total of 390 residues in influenza and 381 in STNA). The active site residues are more highly conserved, in that both the viral and bacterial structures contain an arginine triad, a hydrophobic pocket, a tyrosine and glutamic acid residue at the base of the site and a potential proton-donating aspartic acid. However, differences in binding to O4 and to the glycerol side-chain may reflect the different kinetics employed by the two enzymes.


Molecular genetic basis of pod corn (Tunicate maize).
Pod corn is a classic morphological mutant of maize in which the mature kernels of the cob are covered by glumes, in contrast to generally grown maize varieties in which kernels are naked. Pod corn, known since pre-Columbian times, is the result of a dominant gain-of-function mutation at the Tunicate (Tu) locus. Some classic articles of 20th century maize genetics reported that the mutant Tu locus is complex, but molecular details remained elusive. Here, we show that pod corn is caused by a cis-regulatory mutation and duplication of the ZMM19 MADS-box gene. Although the WT locus contains a single-copy gene that is expressed in vegetative organs only, mutation and duplication of ZMM19 in Tu lead to ectopic expression of the gene in the inflorescences, thus conferring vegetative traits to reproductive organs.


Extending a biologically inspired model of choice: multi-alternatives, nonlinearity and value-based multidimensional choice.
The leaky competing accumulator (LCA) is a biologically inspired model of choice. It describes the processes of leaky accumulation and competition observed in neuronal populations during choice tasks and it accounts for reaction time distributions observed in psychophysical experiments. This paper discusses recent analyses and extensions of the LCA model. First, it reviews the dynamics and examines the conditions that make the model achieve optimal performance. Second, it shows that nonlinearities of the type present in biological neurons improve performance when the number of choice alternatives increases. Third, the model is extended to value-based choice, where it is shown that nonlinearities in the value function explain risk aversion in risky choice and preference reversals in choice between alternatives characterized across multiple dimensions.


Combined Src and aromatase inhibition impairs human breast cancer growth in vivo and bypass pathways are activated in AZD0530-resistant tumors.
Antiestrogens are used to treat estrogen receptor (ER)-alpha-positive breast cancers and cause a p27-dependent G(1) arrest. Estrogen-bound ER recruits Src to mediate proteolysis of p27 and drive cell proliferation. Here, we tested the antitumor efficacy of combined Src and aromatase inhibition for ER-positive breast cancer. Antiproliferative effects of the aromatase inhibitor, anastrozole, and Src inhibitor, AZD0530, alone or in combination were tested in vitro and in vivo on aromatase-transfected MCF-7Arom5 xenografts. Xenografts were analyzed by immunohistochemistry and proteomic analysis to identify potential biomarkers of drug response and resistance. AZD0530 and anastrozole together increased p27 and caused greater G(1) cell cycle arrest than either drug alone. AZD0530 monotherapy initially retarded xenograft growth in vivo, but drug resistance rapidly emerged. Combined anastrozole/AZD0530 reduced drug resistance and showed greater antitumor efficacy in vivo with greater Src and epidermal growth factor receptor inhibition and a greater increase in p27 and reduction of Ki-67 than either drug alone, supporting further evaluation of these putative predictors of response to combined Src/aromatase inhibition in vivo. Anastrozole alone stimulated Src activity both in vitro and in vivo. AZD0530-resistant tumors showed activation of bypass pathways including MEK and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin, raising the possibility that MEK, mammalian target of rapamycin (mTOR), or PI3K inhibitors may augment Src inhibitor efficacy. These data support clinical investigation of anastrozole-AZD0530 therapy for postmenopausal ER-positive breast cancer. Loss of p27 and increased Ki-67 may predict response and further clinical studies should evaluate for activation of bypass pathways including MEK and PI3K pathways during Src inhibitor therapy.


Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase.
Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasis.


Consequences of community water fluoridation cessation for Medicaid-eligible children and adolescents in Juneau, Alaska.
The general aim of this research was to determine whether cessation of community water fluoridation (CWF) increased oral health disparities, as measured by dental caries procedures and restoration costs for children and adolescents. The analysis was based on all Medicaid dental claims records of 0- to 18-year-old patients residing in zip code 99801 (Juneau, Alaska) during an optimal CWF year (2003, n = 853) compared to all claims for the same age group from 2012 (n = 1052), five years after cessation of CWF. A bivariate analysis (Mann-Whitney U test) of the mean number of caries procedures performed per client was conducted in the study groups under both independent CWF conditions. Furthermore, logistic regression was performed using the dependent variables of caries procedures and the cost of caries-related procedures, with adjustments for CWF group, gender, and race. The statistically significant results included a higher mean number of caries-related procedures among 0- to 18-year-old and < 7-year-old patients in the suboptimal CWF group (2.35 vs. 2.02, p < 0.001; 2.68 vs. 2.01, p = 0.004, respectively). The mean caries-related treatment costs per patient were also significantly higher for all age groups, ranging from a 28 to 111% increase among the suboptimal CWF cohorts after adjusting for inflation. The binary logistic regression analysis results indicated a protective effect of optimal CWF for the 0- to 18-year-old and < 7-year-old age groups (OR = 0.748, 95% CI [0.62, 0.90], p = 0.002; OR = 0.699, 95% CI [0.52, 0.95], p = 0.02, respectively). Additionally, the age group that underwent the most dental caries procedures and incurred the highest caries treatment costs on average were those born after CWF cessation. These results expand our understanding of caries epidemiology under CWF cessation conditions and reaffirm that optimal CWF exposure prevents dental decay. These findings can offer fiscal estimates of the cost burden associated with CWF cessation policies and help decision-makers advance oral health, prevent dental caries, and promote equity in oral health outcomes.


Association of retinal vessel caliber to optic disc and cup diameters.
To investigate whether optic disc size is related to retinal venule and arteriole diameters. The population of Beaver Dam, Wisconsin, aged 43 to 86 years were invited to participate in a baseline examination from 1988 to 1990. During this examination, photographs, centered on the optic discs, were taken after pupil dilation. Optic discs and cups were measured from stereoscopic photographs, whereas retinal vessel measurements were taken from a single digitized photograph. Central retinal vein and central retinal arterial equivalents were subsequently calculated. Data for 3887 right eyes are included in the analyses. Narrower retinal venules and arterioles were found in the smaller optic discs controlling for optic cup diameter as well as age, systolic and diastolic blood pressure, refraction, and sex. Central retinal artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001). Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001). The significant reduction in retinal vessel diameters was only apparent for the smallest optic disc sizes. A reduction in retinal vessel diameters was less consistent and not significant for small optic cup sizes. Smallest optic discs were associated with smaller central retinal artery and central retinal vein diameters. This anatomic relationship may be useful as an additional associated indicator for nonarteritic anterior ischemic optic neuropathy as well as for retinal vascular events.


Maximum work extraction and implementation costs for nonequilibrium Maxwell's demons.
We determine the maximum amount of work extractable in finite time by a demon performing continuous measurements on a quadratic Hamiltonian system subjected to thermal fluctuations, in terms of the information extracted from the system. The maximum work demon is found to apply a high-gain continuous feedback involving a Kalman-Bucy estimate of the system state and operates in nonequilibrium. A simple and concrete electrical implementation of the feedback protocol is proposed, which allows for analytic expressions of the flows of energy, entropy, and information inside the demon. This let us show that any implementation of the demon must necessarily include an external power source, which we prove both from classical thermodynamics arguments and from a version of Landauer's memory erasure argument extended to nonequilibrium linear systems.


Can community action improve equity for maternal health and how does it do so? Research findings from Gujarat, India.
Efforts to work with civil society to strengthen community participation and action for health are particularly important in Gujarat, India, given that the state has resources and capacity, but faces challenges in ensuring that services reach those most in need. To contribute to the knowledge base on accountability and maternal health, this study examines the equity effects of community action for maternal health led by Non-Government Organizations (NGOs) on facility deliveries. It then examines the underlying implementation processes with implications for strengthening accountability of maternity care across three districts of Gujarat, India. Community action for maternal health entailed NGOs a) working with community collectives to raise awareness about maternal health entitlements, b) supporting community monitoring of outreach government services, and c) facilitating dialogue with government providers and authorities with report cards based on community monitoring of maternal health. The study combined qualitative data (project documents and 56 stakeholder interviews thematically analyzed) with quantitative data (2395 women's self-reported receipt of information on entitlements and use of services over 3 years of implementation monitored prospectively through household visits). Multivariable logistic regression examined delivery care seeking and equity. In the marginalised districts, women reported substantial increases in receipt of information of entitlements and utilization of antenatal and delivery care. In the marginalized and wealthier districts, a switch from private facilities to public ones was observed for the most vulnerable. Supportive implementation factors included a) alignment among NGO organizational missions, b) participatory development of project tools, c) repeated capacity building and d) government interest in improving utilization and recognition of NGO contributions. Initial challenges included a) confidence and turnover of volunteers, b) complexity of the monitoring tool and c) scepticism from both communities and providers. With capacity and trust building, NGOs supporting community based collectives to monitor health services and engage with health providers and local authorities, over time overcame implementation challenges to strengthen public sector services. These accountability efforts resulted in improvements in utilisation of public sector services and a shift away from private care seeking, particularly for the marginalised.


Generation and characterization of human iPSC lines derived from a Primary Hyperoxaluria Type I patient with p.I244T mutation.
In this work we describe for the first time the generation and characterization of human induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells (PBMCs) and dermal fibroblasts of a Primary Hyperoxaluria Type I (PH1)-diagnosed patient with p.I244T mutation, which is highly prevalent in Canary Islands due to founder effect. Cell reprogramming was performed using non-integrative Sendai viruses containing the Yamanaka factors and the generated PH1-hiPSC lines (PH1-PBMCs-hiPSC4F1 and PH1-Fib-hiPSC4F1) showed normal karyotypes, silencing of the exogenous reprogramming factors, induction of the typical pluripotency-associated markers and in vivo differentiation ability to the three germ layers.