A Conceptual Review of Loneliness in Adults: Qualitative Evidence Synthesis.

The paper reports an evidence synthesis of how loneliness is conceptualised in qualitative studies in adults. Using PRISMA guidelines, our review evaluated exposure to or experiences of loneliness by adults (aged 16+) in any setting as outcomes, processes, or both. Our initial review included any qualitative or mixed-methods study, published or unpublished, in English, from 1945 to 2018, if it employed an identified theory or concept for understanding loneliness. The review was updated to include publications up to November 2020. We used a PEEST (Participants, Exposure, Evaluation, Study Design, Theory) inclusion criteria. Data extraction and quality assessment (CASP) were completed and cross-checked by a second reviewer. The Evidence of Reviews of Qualitative Research (CERQual) was used to evaluate confidence in the findings. We undertook a thematic synthesis using inductive methods for peer-reviewed papers. The evidence identified three types of distinct but overlapping conceptualisations of loneliness: social, emotional, and existential. We have high confidence in the evidence conceptualising social loneliness and moderate confidence in the evidence on emotional and existential loneliness. Our findings provide a more nuanced understanding of these diverse conceptualisations to inform more effective decision-making and intervention development to address the negative wellbeing impacts of loneliness.

The role of social capital in participatory arts for wellbeing: findings from a qualitative systematic review.

BACKGROUND: Social capital is often cited as shaping impacts of participatory arts, although the concept has not been systematically mapped in arts, health and wellbeing contexts. In wider health inequalities research, complex, differential, and sometimes negative impacts of social capital have been recognised. METHODS: This paper maps of social capital concepts in qualitative research as part of the UK What Works for Wellbeing evidence review programme on culture, sport and wellbeing. RESULTS: Studies often cite positive impacts of bonding and, to a lesser extent, bridging social capital. However, reported challenges suggest the need for a critical approach. Forms of linking social capital, such as reframing and political engagement to address social divisions, are less often cited but may be important in participatory arts and wellbeing. CONCLUSIONS: Future research should further specify dimensions of social capital as well as their nuanced effects in arts, and wellbeing contexts.

Risk assessments and structured care interventions for prevention of foot ulceration in diabetes: development and validation of a prognostic model.

BACKGROUND: Diabetes-related foot ulcers give rise to considerable morbidity, generate a high monetary cost for health and social care services and precede the majority of diabetes-related lower extremity amputations. There are many clinical prediction rules in existence to assess risk of foot ulceration but few have been subject to validation. OBJECTIVES: Our objectives were to produce an evidence-based clinical pathway for risk assessment and management of the foot in people with diabetes mellitus to estimate cost-effective monitoring intervals and to perform cost-effectiveness analyses and a value-of-information analysis. DESIGN: We developed and validated a prognostic model using predictive modelling, calibration and discrimination techniques. An overview of systematic reviews already completed was followed by a review of randomised controlled trials of interventions to prevent foot ulceration in diabetes mellitus. A review of the health economic literature was followed by the construction of an economic model, an analysis of the transitional probability of moving from one foot risk state to another, an assessment of cost-effectiveness and a value-of-information analysis. INTERVENTIONS: The effects of simple and complex interventions and different monitoring intervals for the clinical prediction rules were evaluated. MAIN OUTCOME MEASURE: The main outcome was the incidence of foot ulceration. We compared the new clinical prediction rules in conjunction with the most effective preventative interventions at different monitoring intervals with a 'treat-all' strategy. DATA SOURCES: Data from an electronic health record for 26,154 people with diabetes mellitus in one Scottish health board were used to estimate the monitoring interval. The Prediction Of Diabetic foot UlcerationS (PODUS) data set was used to develop and validate the clinical prediction rule. REVIEW METHODS: We searched for eligible randomised controlled trials of interventions using search strategies created for Ovid® (Wolters Kluwer, Alphen aan den Rijn, the Netherlands), MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Randomised controlled trials in progress were identified via the International Standard Randomised Controlled Trial Number Registry and systematic reviews were identified via PROSPERO. Databases were searched from inception to February 2019. RESULTS: The clinical prediction rule was found to accurately assess the risk of foot ulceration. Digital infrared thermometry, complex interventions and therapeutic footwear with offloading devices were found to be effective in preventing foot ulcers. The risk of developing a foot ulcer did not change over time for most people. We found that interventions to prevent foot ulceration may be cost-effective but there is uncertainty about this. Digital infrared thermometry and therapeutic footwear with offloading devices may be cost-effective when used to treat all people with diabetes mellitus regardless of their ulcer risk. LIMITATIONS: The threats to the validity of the results in some randomised controlled trials in the review and the large number of missing data in the electronic health record mean that there is uncertainty in our estimates. CONCLUSIONS: There is evidence that interventions to prevent foot ulceration are effective but it is not clear who would benefit most from receiving the interventions. The ulceration risk does not change over an 8-year period for most people with diabetes mellitus. A change in the monitoring interval from annually to every 2 years for those at low risk would be acceptable. FUTURE WORK RECOMMENDATIONS: Improving the completeness of electronic health records and sharing data would help improve our knowledge about the most clinically effective and cost-effective approaches to prevent foot ulceration in diabetes mellitus. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016052324. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 62. See the NIHR Journals Library website for further project information.

People with diabetes sometimes have problems with their feet that can become serious and make getting around harder and life less enjoyable. We have developed a test based on a simple score to find out a person's risk of getting a foot ulcer. We also wanted to know how often the test needs to be done. People who have been tested and learn that they might go on to have foot problems rightly expect to be given treatment that stops the problem happening in the first place. In this project, we read many written reports about the best treatments to prevent foot ulcers. We found that some things can prevent foot ulcers, such as wearing special shoes and insoles, taking the temperature of the skin of the foot and resting when the temperature rises, and receiving specialist care from diabetes foot care teams. However, we also looked at the costs of the test and treatments and found that some treatments are better value for money than others. By using people's health data from NHS computers, we discovered that very few people with diabetes develop a worse risk score for foot ulcers as time goes on, and it seems that being tested every year is not necessary for everyone. New clinical trials might help to improve foot health for people with diabetes, but if all of the researchers who have collected data from people in clinical trials shared their data it would be possible to find out more about who will gain most from these treatments without spending a lot on new research. It is clear that better input of patients' health data into NHS computers will benefit diabetes research in the future.

Revealing COVID-19 transmission in Australia by SARS-CoV-2 genome sequencing and agent-based modeling.

In January 2020, a novel betacoronavirus (family Coronaviridae), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of a cluster of pneumonia cases occurring in Wuhan City, Hubei Province, China1,2. The disease arising from SARS-CoV-2 infection, coronavirus disease 2019 (COVID-19), subsequently spread rapidly causing a worldwide pandemic. Here we examine the added value of near real-time genome sequencing of SARS-CoV-2 in a subpopulation of infected patients during the first 10 weeks of COVID-19 containment in Australia and compare findings from genomic surveillance with predictions of a computational agent-based model (ABM). Using the Australian census data, the ABM generates over 24 million software agents representing the population of Australia, each with demographic attributes of an anonymous individual. It then simulates transmission of the disease over time, spreading from specific infection sources, using contact rates of individuals within different social contexts. We report that the prospective sequencing of SARS-CoV-2 clarified the probable source of infection in cases where epidemiological links could not be determined, significantly decreased the proportion of COVID-19 cases with contentious links, documented genomically similar cases associated with concurrent transmission in several institutions and identified previously unsuspected links. Only a quarter of sequenced cases appeared to be locally acquired and were concordant with predictions from the ABM. These high-resolution genomic data are crucial to track cases with locally acquired COVID-19 and for timely recognition of independent importations once border restrictions are lifted and trade and travel resume.

Critical reflections on methodological challenge in arts and dementia evaluation and research.

Methodological rigour, or its absence, is often a focus of concern for the emerging field of evaluation and research around arts and dementia. However, this paper suggests that critical attention should also be paid to the way in which individual perceptions, hidden assumptions and underlying social and political structures influence methodological work in the field. Such attention will be particularly important for addressing methodological challenges relating to contextual variability, ethics, value judgement and signification identified through a literature review on this topic. Understanding how, where and when evaluators and researchers experience such challenges may help to identify fruitful approaches for future evaluation.

SNAP-Based Incentive Programs at Farmers' Markets: Adaptation Considerations for Temporary Assistance for Needy Families (TANF) Recipients.

OBJECTIVE: To describe the design, implementation, and consumer response to a coupon-style intervention aimed to increase Supplemental Nutrition Assistance Program (SNAP) use at a farmers' market (FM) among Temporary Assistance for Needy Families (TANF) participants. DESIGN: A quasi-experimental trial to evaluate redemption response to 2 coupon interventions; baseline surveys characterized coupon redeemers and non-redeemers. SETTING: Urban. PARTICIPANTS: The TANF recipients were assigned to either a plain (n = 124) or targeted marketing coupon intervention (n = 130). INTERVENTION(S): Both groups received 10 $2 coupons to double fruit and vegetable SNAP purchases at the FM. The targeted marketing group also received an oral presentation designed to reduce perceived barriers to FM use. MAIN OUTCOME MEASURE: Coupon redemption. ANALYSIS: The researchers used t tests and chi-square/Fisher exact tests to examine associations between redeemers and non-redeemers; logistic regression was used to adjust for the intervention. RESULTS: No male and few female participants redeemed coupons (6.3%). Among women, those with knowledge of vegetable preparation were 3 times more likely to redeem coupons than were those with little or no knowledge (odds ratio = 3.77; 95% confidence interval, 1.03-13.77). CONCLUSIONS AND IMPLICATIONS: Stand-alone coupon incentive programs may not be a high-reach strategy for encouraging FM use among the population using TANF. Complementary strategies to build vegetable preparation knowledge and skills are needed.

Correlation between Cyclin Dependent Kinases and Artemisinin-Induced Dormancy in Plasmodium falciparum In Vitro.

BACKGROUND: Artemisinin-induced dormancy provides a plausible explanation for recrudescence following artemisinin monotherapy. This phenomenon shares similarities with cell cycle arrest where cyclin dependent kinases (CDKs) and cyclins play an important role. METHODS: Transcription profiles of Plasmodium falciparum CDKs and cyclins before and after dihydroartemisinin (DHA) treatment in three parasite lines, and the effect of CDK inhibitors on parasite recovery from DHA-induced dormancy were investigated. RESULTS: After DHA treatment, parasites enter a dormancy phase followed by a recovery phase. During the dormancy phase parasites up-regulate pfcrk1, pfcrk4, pfcyc2 and pfcyc4, and down-regulate pfmrk, pfpk5, pfpk6, pfcrk3, pfcyc1 and pfcyc3. When entering the recovery phase parasites immediately up-regulate all CDK and cyclin genes. Three CDK inhibitors, olomoucine, WR636638 and roscovitine, produced distinct effects on different phases of DHA-induced dormancy, blocking parasites recovery. CONCLUSIONS: The up-regulation of PfCRK1 and PfCRK4, and down regulation of other CDKs and cyclins correlate with parasite survival in the dormant state. Changes in CDK expression are likely to negatively regulate parasite progression from G1 to S phase. These findings provide new insights into the mechanism of artemisinin-induced dormancy and cell cycle regulation of P. falciparum, opening new opportunities for preventing recrudescence following artemisinin treatment.

Farmers' markets and the local food environment: identifying perceived accessibility barriers for SNAP consumers receiving temporary assistance for needy families (TANF) in an urban Oklahoma community.

OBJECTIVE: To examine barriers to farmers' market (FM) use by Supplemental Nutrition Assistance Program (SNAP) consumers receiving Temporary Assistance for Needy Families. DESIGN: Focus groups. SETTING: An urban community in Oklahoma. PARTICIPANTS: Supplemental Nutrition Assistance Program beneficiaries receiving Temporary Assistance for Needy Families (n = 64 across 8 focus groups). PHENOMENON OF INTEREST: Perceptions about FM foods and barriers to FM use. ANALYSIS: Transcript-based content analysis using the 5 dimensions of access framework. RESULTS: Few participants ate fresh produce regularly and most appreciated the convenience of shopping at a supermarket. Farmers' markets were not perceived as available or accommodating to shopping needs and affordability and acceptability concerns were expressed. Few were aware of FMs that accepted SNAP. Emerging themes suggested residential segregation and cultural barriers to FM use. CONCLUSIONS AND IMPLICATIONS: Farmers' market managers, community nutritionists, and researchers should develop interventions that correct common misperceptions about FM products, minimize access barriers, and increase awareness of SNAP payment options. Residential segregation and cultural barriers may have a role in FM use and should be explored further.

Mitochondrial Membrane Potential in a Small Subset of Artemisinin-Induced Dormant Plasmodium falciparum Parasites In Vitro.

Artemisinin-induced dormancy is a proposed mechanism for failures of monotherapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that after dihydroartemisinin treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential marker, and persisted to recovery. RH-positive parasites sorted with fluorescence-activated cell sorting resumed growth at 10,000/well whereas RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was detected only in RH-positive dormant parasites. Importantly, after treatment of dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy.

BACKGROUND: Plasmodium falciparum and Plasmodium vivax are endemic in Vanuatu and the Solomon Islands. While both countries have introduced artemether-lumefantrine (AL) as first-line therapy for both P. falciparum and P. vivax since 2008, chloroquine and sulphadoxine-pyrimethamine (SP) were used as first-line therapy for many years prior to the introduction of AL. Limited data are available on the extent of SP resistance at the time of policy change. METHODS: Blood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an AL therapeutic efficacy study conducted in 2008. Plasmodium vivax and P. falciparum dhfr and dhps genes were sequenced to detect nucleotide polymorphisms. RESULTS: All P. falciparum samples analysed (n=114) possessed a double mutant pfdhfr allele (C59R/S108N). Additionally, mutation A437G in pfhdps was detected in a small number of samples 2/13, 1/17 and 3/26 from Tanna Island, Vanuatu and Temotu and Malaita Provinces Solomon Islands respectively. Mutations were also common in pvdhfr from Tanna Island, Vanuatu, where 33/51 parasites carried the double amino acid substitution S58R/S117N, while in Temotu and Malaita Provinces, Solomon Islands 32/40 and 39/46 isolates carried the quadruple amino acid substitution F57L/S58R/T61M/S117T in DHFR respectively. No mutations in pvdhps (n=108) were detected in these three island groups. CONCLUSION: Prior to the introduction of AL, there was a moderate level of SP resistance in the P. falciparum population that may cause SP treatment failure in young children. Of the P. vivax isolates, a majority of Solomon Islands isolates carried quadruple mutant pvdhfr alleles while a majority of Vanuatu isolates carried double mutant pvdhfr alleles. This suggests a higher level of SP resistance in the P. vivax population in Solomon Islands compared to the sympatric P. falciparum population and there is a higher level of SP resistance in P. vivax parasites from Solomon Islands than Vanuatu. This study demonstrates that the change of treatment policy in these countries from SP to ACT was timely. The information also provides a baseline for future monitoring.

Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands.

BACKGROUND: Chloroquine (CQ), alone or in combination with sulphadoxine-pyrimethamine, was widely used for the treatment of Plasmodium falciparum and Plasmodium vivax for several decades in both Vanuatu and Solomon Islands prior to the introduction of artemether-lumefantrine (AL) in 2008. However, the effect of chloroquine selection on parasite population, which may affect the efficacy of lumefantrine or other partner drugs of artemisinin, has not been well assessed. This study aims to provide baseline data on molecular markers (pfcrt and pfmdr1), along with the origins of pfcrt, prior to the introduction of AL. METHODS: Blood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an artemether-lumefantrine efficacy study in 2008. Plasmodium falciparum pfcrt and pfmdr1 genes were examined for polymorphisms. Microsatellite markers flanking pfcrt were also examined to ascertain origins of CQ resistance. RESULTS: Pfcrt analysis revealed 100% of parasites from Tafea Province, Vanuatu and Malaita Province, Solomon Islands and 98% of parasites from Temotu Province, Solomon Islands carried the K76T polymorphism that confers CQ resistance. Comparison of pfcrt allelic patterns and microsatellite markers flanking pfcrt revealed six haplotypes with more than 70% of isolates possessing haplotypes very similar to those observed in Papua New Guinea. The dominant (98.5%) pfmdr1 allele across all island groups was YYCND. CONCLUSIONS: Prior to the introduction of AL in the Solomon Islands and Vanuatu, P. falciparum isolates possessed point mutations known to confer CQ resistance and possibly associated with a decreased susceptibility to quinine and halofantrine, but an increased susceptibility to artemisinin and lumefantrine. Overall, pfcrt allelic types and the flanking microsatellite markers exhibited similarities to those of Papua New Guinea, suggesting these parasites share a common ancestry. The current use of AL for both P. falciparum and P. vivax infections will enable changes in these markers, in the absence of CQ pressure, to be monitored.

Genetic diversity and population structure of Plasmodium vivax in Central China.

BACKGROUND: In Central China the declining incidence of Plasmodium vivax has been interrupted by epidemic expansions and imported cases. The impact of these changes on the local parasite population, and concurrent risks of future resurgence, was assessed. METHODS: Plasmodium vivax isolates collected from Anhui and Jiangsu provinces, Central China between 2007 and 2010 were genotyped using capillary electrophoresis at seven polymorphic short tandem repeat markers. Spatial and temporal analyses of within-host and population diversity, population structure, and relatedness were conducted on these isolates. RESULTS: Polyclonal infections were infrequent in the 94 isolates from Anhui (4%) and 25 from Jiangsu (12%), with a trend for increasing frequency from 2008 to 2010 (2 to 19%) when combined. Population diversity was high in both provinces and across the years tested (H(E) = 0.8 - 0.85). Differentiation between Anhui and Jiangsu was modest (F'(ST) = 0.1). Several clusters of isolates with identical multi-locus haplotypes were observed across both Anhui and Jiangsu. Linkage disequilibrium was strong in both populations and in each year tested (I(A)(S) = 0.2 - 0.4), but declined two- to four-fold when identical haplotypes were accounted for, indicative of occasional epidemic transmission dynamics. None of five imported isolates shared identical haplotypes to any of the central Chinese isolates. CONCLUSIONS: The population genetic structure of P. vivax in Central China highlights unstable transmission, with limited barriers to gene flow between the central provinces. Despite low endemicity, population diversity remained high, but the reservoirs sustaining this diversity remain unclear. The challenge of imported cases and risks of resurgence emphasize the need for continued surveillance to detect early warning signals. Although parasite genotyping has potential to inform the management of outbreaks, further studies are required to identify suitable marker panels for resolving local from imported P. vivax isolates.

Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province, Solomon Islands.

BACKGROUND: Temotu Province, Solomon Islands is progressing toward malaria elimination. A baseline survey conducted in 2008 showed that most Plasmodium infections in the province were of low parasite density and asymptomatic infections. To better understand mechanisms underlying these malaria transmission characteristics genetic diversity and relationships among Plasmodium falciparum and Plasmodium vivax populations in the province were examined. METHODS: Forty-five P. falciparum and 67 P. vivax samples collected in the 2008 baseline survey were successfully genotyped using eight P. falciparum and seven P. vivax microsatellite markers. Genetic diversity, relationships and distribution of both P. falciparum and P. vivax populations were analysed. RESULTS: Plasmodium falciparum population exhibited low diversity with 19 haplotypes identified and had closely related clusters indicating clonal expansion. Interestingly, a dominant haplotype was significantly associated with fever and high parasite density. In contrast, the P. vivax population was highly diverse with 58 haplotypes identified that were not closely related. Parasite populations between different islands in the province showed low genetic differentiation. CONCLUSION: The low diversity and clonal population of P. falciparum population may partially account for clinical immunity developed against illness. However, it is possible that importation of a new P. falciparum strain was the major cause of illness. High diversity in P. vivax population and low relatedness between strains suggested clinical immunity to P. vivax may be maintained by different mechanisms. The genetic diversity, population structure and distribution of strains indicate that transmission of P. falciparum was low, but that of P. vivax was still high in 2008. These data will be useful for assessing changes in malaria transmission resulting from interventions.

Operational research to inform a sub-national surveillance intervention for malaria elimination in Solomon Islands.

BACKGROUND: Successful reduction of malaria transmission to very low levels has made Isabel Province, Solomon Islands, a target for early elimination by 2014. High malaria transmission in neighbouring provinces and the potential for local asymptomatic infections to cause malaria resurgence highlights the need for sub-national tailoring of surveillance interventions. This study contributes to a situational analysis of malaria in Isabel Province to inform an appropriate surveillance intervention. METHODS: A mixed method study was carried out in Isabel Province in late 2009 and early 2010. The quantitative component was a population-based prevalence survey of 8,554 people from 129 villages, which were selected using a spatially stratified sampling approach to achieve uniform geographical coverage of populated areas. Diagnosis was initially based on Giemsa-stained blood slides followed by molecular analysis using polymerase chain reaction (PCR). Local perceptions and practices related to management of fever and treatment-seeking that would impact a surveillance intervention were also explored using qualitative research methods. RESULTS: Approximately 33% (8,554/26,221) of the population of Isabel Province participated in the survey. Only one subject was found to be infected with Plasmodium falciparum (Pf) (96 parasites/µL) using Giemsa-stained blood films, giving a prevalence of 0.01%. PCR analysis detected a further 13 cases, giving an estimated malaria prevalence of 0.51%. There was a wide geographical distribution of infected subjects. None reported having travelled outside Isabel Province in the previous three months suggesting low-level indigenous malaria transmission. The qualitative findings provide warning signs that the current community vigilance approach to surveillance will not be sufficient to achieve elimination. In addition, fever severity is being used by individuals as an indicator for malaria and a trigger for timely treatment-seeking and case reporting. In light of the finding of a low prevalence of parasitaemia, the current surveillance system may not be able to detect and prevent malaria resurgence. CONCLUSION: An adaption to the malERA surveillance framework is proposed and recommendations made for a tailored provincial-level surveillance intervention, which will be essential to achieve elimination, and to maintain this status while the rest of the country catches up.

The intersection of medical debt and predatory lending among hispanics.

This pilot study explored the link between predatory lending and health care debt among Hispanics. Research shows that links exist between health care costs, debt, poverty, and race ( Draught & Silva, 2003 ; Zeldin & Rukavina, 2007 ). Prior to this study there was no research on the intersection between medical debt and predatory lending although there was reason to believe this link exists ( Seifert, 2004 ). Our results confirm this link and we propose means to break it.

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting.

BACKGROUND: Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. METHODS: During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. RESULTS: A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥ 38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/µL. There was an age correlation for the proportion of parasite density below 100/µL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. CONCLUSION: Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 June 2010 - 31 July 2010.

This article documents the addition of 205 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Bagassa guianensis, Bulweria bulwerii, Camelus bactrianus, Chaenogobius annularis, Creontiades dilutus, Diachasmimorpha tryoni, Dioscorea alata, Euhrychiopsis lecontei, Gmelina arborea, Haliotis discus hannai, Hirtella physophora, Melanaphis sacchari, Munida isos, Thaumastocoris peregrinus and Tuberolachnus salignus. These loci were cross-tested on the following species: Halobaena caerulea, Procellaria aequinoctialis, Oceanodroma monteiroi, Camelus ferus, Creontiades pacificus, Dioscorea rotundata, Dioscorea praehensilis, Dioscorea abyssinica, Dioscorea nummularia, Dioscorea transversa, Dioscorea esculenta, Dioscorea pentaphylla, Dioscorea trifida, Hirtella bicornis, Hirtella glandulosa, Licania alba, Licania canescens, Licania membranaceae, Couepia guianensis and 7 undescribed Thaumastocoris species.

The mechanism responsible for the supraphysiologic gonadotropin surge in females treated with gonadotropin-releasing hormone (GnRH) agonist and primed with GnRH antagonist.

OBJECTIVE: To elucidate the physiologic mechanism responsible for the supraphysiologic gonadotropin release from the pituitary induced by gonadotropin-releasing hormone (GnRH) agonist in female rats primed with GnRH antagonist. DESIGN: Controlled experimental intervention. SETTING: Government research facility. ANIMAL(S): Forty 8-week-old Sprague-Dawley rats. INTERVENTION(S): Forty oophorectomized rats were randomized into four treatment groups of 10: group A, control vehicles; group B, GnRH agonist (leuprolide acetate; 1.7 microg/kg twice a day) on day 4; group C, GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4; or group D, GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4 plus GnRH agonist (1.7 microg/kg twice a day) on day 4. MAIN OUTCOME MEASURE(S): Immunohistochemical methods, Northern and in situ hybridization to quantitate pituitary follicle-stimulating hormone beta (FSH-beta), luteinizing hormone beta (LH-beta), and GnRH receptor (GnRH-R) messenger RNA (mRNA), and receptor protein levels in all treatment groups. RESULT(S): Treatment with GnRH antagonist was associated with increased storage of gonadotropin in the pituitary for FSH-beta and LH-beta, but mRNA levels were unchanged. The GnRH-R mRNA decreased after GnRH-agonist treatment but remained stable in the GnRH-antagonist treatment groups. Levels of GnRH-R were decreased after GnRH-antagonist treatment. CONCLUSION(S): These data indicate that the in vivo mechanism responsible for the exaggerated release of gonadotropins in rats primed with GnRH antagonist and treated with GnRH agonist was an increase in releasable gonadotropin pools coupled with a reduction in GnRH-R, but receptor function was preserved.

Early responses of insulin signaling to high-carbohydrate and high-fat overfeeding.

BACKGROUND: Early molecular changes of nutritionally-induced insulin resistance are still enigmatic. It is also unclear if acute overnutrition alone can alter insulin signaling in humans or if the macronutrient composition of the diet can modulate such effects. METHODS: To investigate the molecular correlates of metabolic adaptation to either high-carbohydrate (HC) or high-fat (HF) overfeeding, we conducted overfeeding studies in 21 healthy lean (BMI < 25) individuals (10 women, 11 men), age 20-45, with normal glucose metabolism and no family history of diabetes. Subjects were studied first following a 5-day eucaloric (EC) diet (30% fat, 50% CHO, 20% protein) and then in a counter balanced manner after 5 days of 40% overfeeding of both a HC (20% fat, 60% CHO) diet and a HF (50% fat, 30% CHO) diet. At the end of each diet phase, in vivo insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp technique. Ex vivo insulin action was measured from skeletal muscle tissue samples obtained 15 minutes after insulin infusion was initiated. RESULTS: Overall there was no change in whole-body insulin sensitivity as measured by glucose disposal rate (GDR, EC: 12.1 ± 4.7; HC: 10.9 ± 2.7; HF: 10.8 ± 3.4). Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p < 0.001) and increased IRS-1-associated phosphatidylinositol 3 (PI 3)-kinase activity (p < 0.001) following HC overfeeding. In contrast, HF overfeeding increased skeletal muscle serine phosophorylation of IRS-1 (p < 0.001) and increased total expression of p85α (P < 0.001). CONCLUSION: We conclude that acute bouts of overnutrition lead to changes at the cellular level before whole-body insulin sensitivity is altered. On a signaling level, HC overfeeding resulted in changes compatible with increased insulin sensitivity. In contrast, molecular changes in HF overfeeding were compatible with a reduced insulin sensitivity.

Monsoon-influenced speciation patterns in a species flock of Eophreatoicus Nicholls (Isopoda; Crustacea).

A species flock of the freshwater isopod genus Eophreatoicus Nicholls lives in seeps, springs and perched aquifers at the base of the Arnhem Plateau and associated sandstone outliers in Australia's Northern Territory. These species have been found to have surprisingly high levels of genetic divergence and narrow range endemism, despite potential opportunities for dispersion during the summer monsoon season when streams flow continuously and have connectivity. Species of Eophreatoicus were identified morphologically as distinct taxa, sometimes with two or three species occurring at the same site. DNA sequence data from the mitochondrial 16S rRNA and cytochrome c oxidase subunit I genes corroborate our morphological concepts to a high level of resolution, with the exception of two distinct species that are identical genetically. The value of mtDNA data for identification of these species, therefore, is limited. These isopods disperse downstream from their home springs to a limited extent during the wet season, but the genetic data show that migration to non-natal springs, and reproduction there, may be rare. We argue that the multiplication of the narrow-range endemic species is the result of their homing behaviour combined with monsoonal alternation between aridity and flooding over recent and geological time scales since the Miocene period.