Thyroid Hemiagenesis: Narrative Review and Clinical Implications

Thyroid Hemiagenesis (THA) is an uncommon, congenital anomaly defined by the absence of one thyroid lobe with or without the isthmus. Reports suggest it may be found more often in regions endemic for hypothyroidism. Genetic abnormalities are thought to have a role based on findings in monozygotic twins. Most cases are sporadic, however familiar clusters have also been documented. It is found more frequently in females. A majority of patients report no symptoms and THA is found incidentally during investigations or intraoperatively. THA is usually associated with normal thyroid function, but it can present with thyroid hypofunction. Since a majority of patients are asymptomatic, there are no specific recommendations for management. Ultrasound imaging and thyroid scintigraphy using technetium or iodine are useful in diagnosis. Its clinical importance occurs when the remnant thyroid lobe requires excision leading to the lifelong requirement for thyroxine supplementation. Published English literature (Medline, PubMed, and Embase databases) was searched. Medical subject headings (MeSH) terms used were “thyroid hemiagenesis,” “one thyroid lobe,” and “thyroid aplasia”. Case reports, case series, and original articles were selected to provide a framework for this review. Articles reviewed were published in the past 20 years. The association of THA with thyroid cancer was explored. In this group, the F:M ratio was 3.25:1. Left THA constituted 53% of cases, right THA in 29.4%, and isthmus absence in 17.6% of cases. Also, the authors investigated the link between THA and hyperparathyroidism, both left and right THA are seen in an equal number of cases in the hyperparathyroidism subgroup. In patients with THA and Grave’s disease, left THA was seen in a majority of cases (86.7%), while an equal number of left and right THA was observed in patients with Hashimoto’s thyroiditis. In addition, congenital abnormalities associated with THA were observed, the left THA was seen in 60% and right THA in 40% of cases of this subgroup. The summative review provided a detailed insight into the epidemiology, aetiopathogenesis, genetics, symptomatology, diagnosis, and treatment for THA by combining findings and results from almost a hundred research papers from around the world. THA remains a poorly understood, often incidentally detected, abnormality in euthyroid patients undergoing investigations and treatment for other thyroid disorders

Relational approaches to poverty in rural India: social, ecological and technical dynamics

Poverty is now widely recognised as multidimensional, with indicators including healthcare, housing and sanitation. Yet, relational approaches that foreground political-cultural processes remain marginalised in policy discourses. Focusing on India, we review a wide range of relational approaches to rural poverty. Beginning with early approaches that focus on structural reproduction of class, caste and to a lesser extent gender inequality, we examine new relational approaches developed in the last two decades. The new approaches examine diverse ways in which poverty is experienced and shapes mobilisations against deprivation. They draw attention to poor people’s own articulations of deprivation and alternate conceptions of well-being. They also show how intersecting inequalities of class, caste and gender shape governance practices and political movements. Despite these important contributions, the new relational approaches pay limited attention to technologies and ecologies in shaping the experience of poverty. Reviewing studies on the Green Revolution and wider agrarian transformations in India, we then sketch the outlines of a hybrid relational approach to poverty that combines socio-technical and -ecological dynamics. We argue that such an approach is crucial to challenge narrow economising discourses on poverty and to bridge the policy silos of poverty alleviation and (environmentally) sustainable development

Lampe1: An ENU-Germline Mutation Causing Spontaneous Hepatosteatosis Identified through Targeted Exon-Enrichment and Next-Generation Sequencing

Using a small scale ENU mutagenesis approach we identified a recessive germline mutant, designated Lampe1 that exhibited growth retardation and spontaneous hepatosteatosis. Low resolution mapping based on 20 intercrossed Lampe1 mice revealed linkage to a ∼14 Mb interval on the distal site of chromosome 11 containing a total of 285 genes. Exons and 50 bp flanking sequences within the critical region were enriched with sequence capture microarrays and subsequently analyzed by next-generation sequencing. Using this approach 98.1 percent of the targeted DNA was covered with a depth of 10 or more reads per nucleotide and 3 homozygote mutations were identified. Two mutations represented intronic nucleotide changes whereas one mutation affected a splice donor site in intron 11–12 of Palmitoyl Acetyl-coenzyme A oxygenase-1 (Acox1), causing skipping of exon 12. Phenotyping of Acox1Lampe1 mutants revealed a progression from hepatosteatosis to steatohepatitis, and ultimately hepatocellular carcinoma. The current approach provides a highly efficient and affordable method to identify causative mutations induced by ENU mutagenesis and animal models relevant to human pathology

Youth futures and a masculine development ethos in the regional story of Uttarakhand

Research on the Uttarakhand region, which became a new state in 2000, has focused largely on agrarian livelihoods, religious rituals, development demands, ecological politics and the role of women in regional social movements. This essay discusses another dimension of the regional imaginary—that of a masculine development ethos. Based on ethnographic research and print media sources, this essay focuses on stories, politics, mobilities and imaginations of young men in the years immediately after the achievement of statehood. Despite increased outmigration of youth in search of employment, many young men expressed the dream of maintaining livelihoods in the familiar towns and rural spaces of Uttarakhand, describing their home region as a source of power and agency. In rallies and in print media, young (mostly upper caste) men expressed their disillusionment with the government and the promises of statehood, arguing that their aspirations for development and employment were left unfulfilled. Gendered stories of the region, told in Hindi in rallies and print media, contained references to local places, people and historical events and were produced through local connections and know-how, fostering a regional youth politics. The article argues that Uttarakhand as a region is shaped by the politics of local actors as well as embodied forms of aspiration, affiliation and mobility.IS

Sensor-based precision nutrient and irrigation management enhances the physiological performance, water productivity, and yield of soybean under system of crop intensification

Sensor-based decision tools provide a quick assessment of nutritional and physiological health status of crop, thereby enhancing the crop productivity. Therefore, a 2-year field study was undertaken with precision nutrient and irrigation management under system of crop intensification (SCI) to understand the applicability of sensor-based decision tools in improving the physiological performance, water productivity, and seed yield of soybean crop. The experiment consisted of three irrigation regimes [I1: standard flood irrigation at 50% depletion of available soil moisture (DASM) (FI), I2: sprinkler irrigation at 80% ETC (crop evapo-transpiration) (Spr 80% ETC), and I3: sprinkler irrigation at 60% ETC (Spr 60% ETC)] assigned in main plots, with five precision nutrient management (PNM) practices{PNM1-[SCI protocol], PNM2-[RDF, recommended dose of fertilizer: basal dose incorporated (50% N, full dose of P and K)], PNM3-[RDF: basal dose point placement (BDP) (50% N, full dose of P and K)], PNM4-[75% RDF: BDP (50% N, full dose of P and K)] and PNM5-[50% RDF: BDP (50% N, full P and K)]} assigned in sub-plots using a split-plot design with three replications. The remaining 50% N was top-dressed through SPAD assistance for all the PNM practices. Results showed that the adoption of Spr 80% ETC resulted in an increment of 25.6%, 17.6%, 35.4%, and 17.5% in net-photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), and intercellular CO2 concentration (Ci), respectively, over FI. Among PNM plots, adoption of PNM3 resulted in a significant (p=0.05) improvement in photosynthetic characters like Pn (15.69 µ mol CO2 m−2 s−1), Tr (7.03 m mol H2O m−2 s−1), Gs (0.175 µmol CO2 mol−1 year−1), and Ci (271.7 mol H2O m2 s−1). Enhancement in SPAD (27% and 30%) and normalized difference vegetation index (NDVI) (42% and 52%) values were observed with nitrogen (N) top dressing through SPAD-guided nutrient management, helped enhance crop growth indices, coupled with better dry matter partitioning and interception of sunlight. Canopy temperature depression (CTD) in soybean reduced by 3.09–4.66°C due to adoption of sprinkler irrigation. Likewise, Spr 60% ETc recorded highest irrigation water productivity (1.08 kg ha−1 m−3). However, economic water productivity (27.5 INR ha−1 m−3) and water-use efficiency (7.6 kg ha−1 mm−1 day−1) of soybean got enhanced under Spr 80% ETc over conventional cultivation. Multiple correlation and PCA showed a positive correlation between physiological, growth, and yield parameters of soybean. Concurrently, the adoption of Spr 80% ETC with PNM3 recorded significantly higher grain yield (2.63 t ha−1) and biological yield (8.37 t ha−1) over other combinations. Thus, the performance of SCI protocols under sprinkler irrigation was found to be superior over conventional practices. Hence, integrating SCI with sensor-based precision nutrient and irrigation management could be a viable option for enhancing the crop productivity and enhance the resource-use efficiency in soybean under similar agro-ecological regions

Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors

Highway increases concentrations of toxic metals in giant panda habitat

The Qinling panda subspecies (Ailuropoda melanoleuca qinlingensis) is highly endangered with fewer than 350 individuals inhabiting the Qinling Mountains. Previous studies have indicated that giant pandas are exposed to heavy metals, and a possible source is vehicle emission. The concentrations of Cu, Zn, Mn, Pb, Cr, Ni, Cd, Hg, and As in soil samples collected from sites along a major highway bisecting the panda's habitat were analyzed to investigate whether the highway was an important source of metal contamination. There were 11 sites along a 30-km stretch of the 108th National Highway, and at each site, soil samples were taken at four distances from the highway (0, 50, 100, and 300 m) and at three soil depths (0, 5, 10 cm). Concentrations of all metals except As exceeded background levels, and concentrations of Cu, Zn, Mn, Pb, and Cd decreased significantly with increasing distance from the highway. Geo-accumulation index indicated that topsoil next to the highway was moderately contaminated with Pb and Zn, whereas topsoil up to 300 m away from the highway was extremely contaminated with Cd. The potential ecological risk index demonstrated that this area was in a high degree of ecological hazards, which were also due to serious Cd contamination. And, the hazard quotient indicated that Cd, Pb, and Mn especially Cd could pose the health risk to giant pandas. Multivariate analyses demonstrated that the highway was the main source of Cd, Pb, and Zn and also put some influence on Mn. The study has confirmed that traffic does contaminate roadside soils and poses a potential threat to the health of pandas. This should not be ignored when the conservation and management of pandas is considered

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)