A scientometric analysis of birth cohorts in South Asia: Way forward for Pakistan

The present study aims to: a) systematically map the of birth cohort studies from the South Asian region b) examine the major research foci and landmark contributions from these cohorts using reproducible scientometric techniques and c) offer recommendations on establishing new birth cohorts in Pakistan, building upon the strengths, weaknesses and gaps of previous cohorts. Bibliographic records for a total of 260 articles, published during through December 2018, were retrieved from the Web of Science (core database). All data were analysed using Microsoft Excel (2013), Web of Science platform and CiteSpace. A series of network analysis were then run for each time-period using the link reduction method and pathfinder network scaling. The co-cited articles were clustered into their homogeneous research clusters. The clusters were named using the Latent Semantic Indexing (LSI) method that utilized author keywords as source of names for these clusters. The scientometric analyses of original research output from these birth cohorts also paint a pessimistic landscape in Pakistan- where Pakistani sites for birth cohorts contributed only 31 publications; a majority of these utilized the MAL-ED birth cohort data. A majority of original studies were published from birth cohorts in India (156), Bangladesh (63), and Nepal (15). Out of these contributions, 31 studies reported data from multiple countries. The three major birth cohorts include prospective and multi-country MAL-ED birth cohort and The Pakistan Early Childhood Development Scale Up Trial, and a retrospective Maternal and infant nutrition intervention cohort. In addition to these, a few small-scale birth cohorts reported findings pertaining to neonatal sepsis, intrauterine growth retardation and its effects on linear growth of children and environmental enteropathy

Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p \u3c 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials

Cloning whole bacterial genomes in yeast

Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Beyond Poisson : increased spike-time regularity across primate parietal dortex

Cortical areas differ in their patterns of connectivity, cellular composition, and functional architecture. Spike trains, on the other hand, are commonly assumedto follow similarly irregulardynamics across neocortex. We examined spike-time statistics in four parietal areas using a method that accounts for nonstationarities in firing rate. We found that, whereas neurons in visual areas fire irregularly, many cells in association and motor-like parietal regions show increasingly regular spike trains by comparison. Regularity was evident both in the shape of interspike interval distributions and in spike-count variability across trials. Thus, Poisson-like randomness is not a universal feature of neocortex. Rather, many parietal cells have reduced trial-to-trial variability in spike counts that could provide for more reliable firing-rate signals. These results suggest that spiking dynamics may play different roles in different cortical areas and should not be assumed to arise from fundamentally irreducible noise sources

The two publics and institutional theory – a study of public sector accounting in Tanzania

This paper summarises, and attempts to theorise, the findings of a series of research projects investigating accounting practices across the public sector in Tanzania. Data was collected principally by interviewing participants in central and local government and in a number of NGO's. Analysis was undertaken using grounded theory methods, alongside a theoretical framework. This framework comprised the work of the post-colonial theorist Ekeh, 1975, Ekeh, 1994a and Ekeh, 1994b and the concepts of legitimacy, loose coupling and isomorphism from institutional theory. Legitimacy and loose coupling were central concerns in all the institutions and played a significant role in understanding their accounting practices. However, there were significant differences between the settings’ responses. These can be partly explained as responses to different isomorphistic pressures. Differences between institutions can be further explained using Ekeh's concepts of the primordial and the civic publics. Gaming and corruption were evident in central government, associated more with the civic public. Accountability and a sense of moral responsibility appeared to be stronger in NGOs, which were more closely associated with the primordial public. In contrast to the central government, which was associated more with the civic public, accounting was extremely problematic resulting in many dysfunctional practices. However gaming and corruption were most evident in local government where participants were subject to a conflict between the two publics’ moralities