Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: A case report

BACKGROUND: Coexistence of cancer and tuberculosis in axillary lymph nodes is rare. Only seven cases have been reported in the literature. CASE REPORT: We report here a case of infiltrating ductal carcinoma breast metastasizing to the axillary lymph node along with tubercular granuloma in the same lymph node without primary mammary or pulmonary tuberculosis. CONCLUSION: Primary tuberculosis coexisting with carcinoma is of rare occurrence. A possibility should always be borne in mind especially in patients from endemic areas

Carrier Transport in High Mobility InAs Nanowire Junctionless Transistors

Ability to understand and model the performance limits of nanowire transistors is the key to design of next generation devices. Here, we report studies on high-mobility junction-less gate-all-around nanowire field effect transistor with carrier mobility reaching 2000 cm2/V.s at room temperature. Temperature-dependent transport measurements reveal activated transport at low temperatures due to surface donors, while at room temperature the transport shows a diffusive behavior. From the conductivity data, the extracted value of sound velocity in InAs nanowires is found to be an order less than the bulk. This low sound velocity is attributed to the extended crystal defects that ubiquitously appear in these nanowires. Analyzing the temperature-dependent mobility data, we identify the key scattering mechanisms limiting the carrier transport in these nanowires. Finally, using these scattering models, we perform drift-diffusion based transport simulations of a nanowire field-effect transistor and compare the device performances with experimental measurements. Our device modeling provides insight into performance limits of InAs nanowire transistors and can be used as a predictive methodology for nanowire-based integrated circuits.Comment: 22 pages, 5 Figures, Nano Letter

Spatial distribution of outbreak of locust swarms: a geographical analysis of vulnerability and preventions in India

Current outbreak of locust swarms in the different parts of the world has also emerged as a big problem for the Indian agricultural sector and associated livelihood options. Being known for its transient nature, the locust swarms containing millions of locusts. These swarms are, therefore, one of the most dangerous pests in the world that may have a disastrous impact on food, food crops, fodder and food security around the world. The outbreak has been historically noticed in several regions of the world which effected the agriculture system of the many countries and major cause for the slowdown in the economy. This paper examines the origin and migration trends of locust swarms in the world in general and India in particular.  Also paper evaluates the recent outbreak of locusts in India along with assessing its devastating impact on Indian Agricultural Sector and the track routes of the swarms in India in different months. In the end, the paper highlights preventive measures that have been used in monitoring and preventions of locust swarms. The outbreaks of locust in India is not new, but have been encountered in the past too. The intensity and number of hives and migratory frequency is increasing with time. The Area, magnitude and impacts of the locust swarms is also growing with time and space. Since the outbreak results in social, economic and environmental consequences, therefore, adequate measures and planning are required to tackle the crisis.Keywords:  Locusts, Swarms, Vulnerability, Prevention Measures, Spatial distributio

Identification of publicly available data sources to inform the conduct of Health Technology Assessment in India

Background: Health technology assessment (HTA) provides a globally-accepted and structured approach to synthesising evidence for cost and clinical effectiveness alongside ethical and equity considerations to inform evidence-based priorities. India is one of the most recent countries to formally commit to institutionalising HTA as an integral component of the heath resource allocation decision-making process. The effective conduct of HTA depends on the availability of reliable data. Methods: We draw from our experience of collecting, synthesizing, and analysing health-related datasets in India and internationally, to highlight the complex requirements for undertaking HTA, and explore the availability of such data in India. We first outlined each of the core data components required for the conduct of HTA, and their availability in India, drawing attention to where data can be accessed, and different ways in which researchers can overcome the challenges of missing or low quality data. Results: We grouped data into the following categories: clinical efficacy; cost; epidemiology; quality of life; service use/consumption; and equity. We identified numerous large local data sources containing epidemiological information. There was a marked absence of other locally-collected data necessary for informing HTA, particularly data relating to cost, service use, and quality of life. Conclusions: The introduction of HTA into the health policy space in India provides an opportunity to comprehensively assess the availability and quality of health data capture across the country. While epidemiological information is routinely collected across India, other data inputs necessary for HTA are not readily available. This poses a significant bottleneck to the efficient generation and deployment of HTA into the health decision space. Overcoming these data gaps by strengthening the routine collection of comprehensive and verifiable health data will have important implications not only for embedding economic analyses into the priority setting process, but for strengthening the health system as a whole

Inactivation of VCP/ter94 Suppresses Retinal Pathology Caused by Misfolded Rhodopsin in Drosophila

The most common Rhodopsin (Rh) mutation associated with autosomal dominant retinitis pigmentosa (ADRP) in North America is the substitution of proline 23 by histidine (RhP23H). Unlike the wild-type Rh, mutant RhP23H exhibits folding defects and forms intracellular aggregates. The mechanisms responsible for the recognition and clearance of misfolded RhP23H and their relevance to photoreceptor neuron (PN) degeneration are poorly understood. Folding-deficient membrane proteins are subjected to Endoplasmic Reticulum (ER) quality control, and we have recently shown that RhP23H is a substrate of the ER–associated degradation (ERAD) effector VCP/ter94, a chaperone that extracts misfolded proteins from the ER (a process called retrotranslocation) and facilitates their proteasomal degradation. Here, we used Drosophila, in which Rh1P37H (the equivalent of mammalian RhP23H) is expressed in PNs, and found that the endogenous Rh1 is required for Rh1P37H toxicity. Genetic inactivation of VCP increased the levels of misfolded Rh1P37H and further activated the Ire1/Xbp1 ER stress pathway in the Rh1P37H retina. Despite this, Rh1P37H flies with decreased VCP function displayed a potent suppression of retinal degeneration and blindness, indicating that VCP activity promotes neurodegeneration in the Rh1P37H retina. Pharmacological treatment of Rh1P37H flies with the VCP/ERAD inhibitor Eeyarestatin I or with the proteasome inhibitor MG132 also led to a strong suppression of retinal degeneration. Collectively, our findings raise the possibility that excessive retrotranslocation and/or degradation of visual pigment is a primary cause of PN degeneration

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.

GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism. GEMIN5 mutations result in disruption of snRNP complex assembly formation in patient iPSC neurons. Furthermore, knock down of rigor mortis, the fly homolog of human GEMIN5, leads to developmental defects, motor dysfunction, and a reduced lifespan. Interestingly, we observed that GEMIN5 variants disrupt a distinct set of transcripts and pathways as compared to SMA patient neurons, suggesting different molecular pathomechanisms. These findings collectively provide evidence that pathogenic variants in GEMIN5 perturb physiological functions and result in a neurodevelopmental delay and ataxia syndrome