Seasonal distribution of anti-malarial drug resistance alleles on the island of Sumba, Indonesia

Background: Drug resistant malaria poses an increasing public health problem in Indonesia, especially eastern Indonesia, where malaria is highly endemic. Widespread chloroquine (CQ) resistance and increasing sulphadoxine-pyrimethamine (SP) resistance prompted Indonesia to adopt artemisinin-based combination therapy (ACT) as first-line therapy in 2004. To help develop a suitable malaria control programme in the district of West Sumba, the seasonal distribution of alleles known to be\ud associated with resistance to CQ and SP among\ud Plasmodium falciparum isolates from the region was investigated.\ud Methods: Plasmodium falciparum isolates were collected during malariometric surveys in the wet and dry seasons in 2007 using two-stage cluster sampling. Analysis of pfcrt, pfmdr, pfmdr1 gene copy number, dhfr, and dhps genes were done using protocols described previously.\ud Results and Discussion: The 76T allele of the pfcrt gene is nearing fixation in this population. Pfmdr1 mutant alleles occurred in 72.8% and 53.3%, predominantly as 1042D and 86Y alleles that are mutuallyexclusive. The prevalence of amplified\ud pfmdr1 was found 41.9% and 42.8% of isolates in the wet and dryseasons, respectively. The frequency of dhfr mutant alleles was much lower, either as a single 108N mutation or paired with 59R. The 437G allele was the only mutant dhps allele detected and it was only found during dry season.\ud Conclusion: The findings demonstrate a slighly higher distribution of drug-resistant alleles during the wet season and support the policy of replacing CQ with ACT in this area, but suggest that SP might still be effective either alone or in combination with other anti-malarial

Neuroethics and fMRI: Mapping a Fledgling Relationship

Human functional magnetic resonance imaging (fMRI) informs the understanding of the neural basis of mental function and is a key domain of ethical enquiry. It raises questions about the practice and implications of research, and reflexively informs ethics through the empirical investigation of moral judgments. It is at the centre of debate surrounding the importance of neuroscience findings for concepts such as personhood and free will, and the extent of their practical consequences. Here, we map the landscape of fMRI and neuroethics, using citation analysis to uncover salient topics. We find that this landscape is sparsely populated: despite previous calls for debate, there are few articles that discuss both fMRI and ethical, legal, or social implications (ELSI), and even fewer direct citations between the two literatures. Recognizing that practical barriers exist to integrating ELSI discussion into the research literature, we argue nonetheless that the ethical challenges of fMRI, and controversy over its conceptual and practical implications, make this essential

Grafting versus seed propagated apricot populations: two main gene pools in Tunisia evidenced by SSR markers and model-based Bayesian clustering

Apricot was introduced into the Mediterranean Basin from China and Asian mountains through the Middle-East and the Central Europe. Traditionally present in Tunisia, we were interested in accessing the origin of apricot species in the country, and in particular in the number and the location of its introductions. A set of 82 representative apricot accessions including 49 grafted cultivars and 33 seed propagated ‘Bargougs’ were genotyped using 24 microsatellite loci revealing a total of 135 alleles. The model-based Bayesian clustering analysis using both Structure and InStruct programs as well as the multivariate method revealed five distinct genetic clusters. The genetic differentiation among clusters showed that cluster 1, with only four cultivars, was the most differentiated from the four remaining genetic clusters, which constituted the largest part of the studied germplasm. According to their geographic origin, the five identified groups (north, centre, south, Gafsa oasis and other oases groups) enclosed a similar variation within group, with a low level of differentiation. Overall results highlighted the distinction of two apricot gene pools in Tunisia related to the different mode of propagation of the cultivars: grafted and seed propagated apricot, which enclosed a narrow genetic basis. Our findings support the assumption that grafting and seed propagated apricots shared the same origin

Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or as Boost following a Multiclade HIV-1 DNA Vaccine in Africa

We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.ClinicalTrials.gov NCT00124007

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Deliberate self-harm and attachment: mediating and moderating roles of depression, anxiety, social support and interpersonal problems among Pakistani school going adolescents

Introduction: In Pakistan there is dearth of research on deliberate self-harm (DSH) and its predictors among adolescents. While the lack of research in Pakistan can be partly attributed to the sacrilegious status, criminalization and stigmatization attached to DSH, it is also an attribute of paucity of Urdu versions of the standardized psychological instruments. Previous research in developed countries has indicated that attachment theory can be used as a useful framework to understand the development of austere psychopathologies like DSH, as well as for studying pathways of interaction of interpersonal and intrapersonal factors of psychopathologies. In this study, standardized psychological instruments are translated into Urdu language as a first step. These instruments are then used to study pathways of interaction of interpersonal and intrapersonal factors of DSH, conceptualized within attachment framework. Method: The study was conducted in two steps. In step 1, Youth Health Risk Behavior Survey (YHRB), Inventory of Interpersonal Problems-32 (IIP-32) and Significant Others Scale (SOS), were translated into Urdu language. Along with these scales, Urdu translated versions of Hospital Anxiety and Depression Scale (HADS), Adolescent Relationship Scales Questionnaire (ARSQ), Life Events scale (LES) from CASE questionnaire and Family Affluence Scale-II (FAS-II) were reviewed for accuracy of translation through expert judgement and psychometric evaluation. Secondly, a cross sectional survey was conducted with 1290 adolescents (10 - 19 years age) using the translated Urdu versions of the instruments and demographic pro forma. Structural equation modelling was used to study the pathways of associations between predictors of DSH. Results: The extensive process of translation resulted in establishment of semantic, content, technical and construct equivalence of the translated instruments with the original English versions. Multiple imputation was performed to account for missing values in SPSS 20. Important structural adaptations were made in the scales based on factor analyses conducted in M plus. After modifications, all scales showed satisfactory CFI (≥ 0.90) and RMSEA (≤ 0.06). Results of the survey indicated that the prevalence of DSH (with, without and ambivalent suicidal intentions) was 7%. Two SEM models were constructed involving both mediation and moderation pathways. Results of Model 1 showed association of attachment with DSH was double mediated by social support, depression and anxiety. Model 2 also confirmed association of attachment with DSH with double mediation through relationship style problems, depression and anxiety. In order to understand the contextual picture of the concepts studied in this research both SEM models were also constructed by controlling for demographic factors. This resulted in confirming age, gender and family affluence as significant contributors but with very small effects. Discussion and conclusion: In the present study translation of the instruments helped in building a reservoir for future research. The results of translation and validation of instruments indicated that cultural differences, language needs and age must be accounted for while using standardized psychological instruments. Taking into consideration specific cultural and demographic background of Pakistan, this study also confirms the key role of attachment in influencing interaction of predictors of DSH. It is suggested that intrapersonal and interpersonal factors are influential points of intervention for designing clinical, school and community based awareness and prevention programs for DSH. The thesis also discusses the implications for policy guidelines along with recommendations for future research and other applications of the study

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Rare case of combined small cell lung cancer with adenocarcinoma and squamous cell carcinoma

Combined small cell lung cancer (cSCLC) is relatively unusual. We report a case of cSCLC in a 78-year-old man with no prior medical history who presented for evaluation of right upper lobe (RUL) lung mass. A CT scan showed a 3.0 × 2.5 × 2.3 cm RUL lung mass with mildly prominent mediastinal and hilar lymphadenopathy. A right thoracotomy with right upper lobectomy and lymphadenectomy was performed. Histological examination and immunohistochemical stains confirmed the diagnosis of combined small cell lung carcinoma (SCLC) with adenocarcinoma (AC) and squamous cell carcinoma (SCC) components.While there are available guidelines for treating SCLC, the optimal treatment for cSCLC which will improve prognosis has not been adequately determined. We report a very rare category of primary lung malignant neoplasm to represent our institution's experience in diagnosing and managing this type of rare case