Where has Octvia Hill gone? : not as far as you might think

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1991.Includes bibliographical references (leaves 99-105).by Paul M. Lambert.M.C.P

A multi-state model incorporating estimation of excess hazards and multiple time scales

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population-level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multi-state models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, by allowing is to directly quantify the excess risk. This paper proposes a combination of these two frameworks, providing one approach to address (1)-(3). Using recently developed methods in multi-state modeling, we incorporate estimation of excess hazards into a multi-state model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user-friendly Stata software with accompanying example code

The Zwicky Transient Facility Observing System

The Zwicky Transient Facility (ZTF) is a synoptic optical survey for high-cadence time-domain astronomy. Building upon the experience and infrastructure of the highly successful Palomar Transient Factory (PTF) team, ZTF will survey more than an order of magnitude faster than PTF in sky area and volume in order to identify rare, rapidly varying optical sources. These sources will include a trove of supernovae, exotic explosive transients, unusual stellar variables, compact binaries, active galactic nuclei, and asteroids. The single-visit depth of 20.4 mag is well matched to spectroscopic follow-up observations, while the co-added images will provide wide sky coverage 1.5 – 2 mag deeper than SDSS. The ZTF survey will cover the entire Northern Sky and revisit fields on timescales of a few hours, providing hundreds of visits per field each year, an unprecedented cadence, as required to detect fast transients and variability. This high-cadence survey is enabled by an observing system based on a new camera having 47 deg^2 field of view – a factor of 6.5 greater than the existing PTF camera - equipped with fast readout electronics, a large, fast exposure shutter, faster telescope and dome drives, and various measures to optimize delivered image quality. Our project has already received an initial procurement of e2v wafer-scale CCDs and we are currently fabricating the camera cryostat. International partners and the NSF committed funds in June 2014 so construction can proceed as planned to commence engineering commissioning in 2016 and begin operations in 2017. Public release will allow broad utilization of these data by the US astronomical community. ZTF will also promote the development of transient and variable science methods in preparation for the seminal first light of LSST

\u27Links2HealthierBubs\u27 cohort study: Protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women

Introduction: Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. Methods and analysis: ‘Links2HealthierBubs’ is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. Ethics and dissemination: Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women’s Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public

Community Code Verification Exercise for Simulating Sequences of Earthquakes and Aseismic Slip (SEAS)

Numerical simulations of sequences of earthquakes and aseismic slip (SEAS) have made great progress over past decades to address important questions in earthquake physics. However, significant challenges in SEAS modeling remain in resolving multiscale interactions between earthquake nucleation, dynamic rupture, and aseismic slip, and understanding physical factors controlling observables such as seismicity and ground deformation. The increasing complexity of SEAS modeling calls for extensive efforts to verify codes and advance these simulations with rigor, reproducibility, and broadened impact. In 2018, we initiated a community code‐verification exercise for SEAS simulations, supported by the Southern California Earthquake Center. Here, we report the findings from our first two benchmark problems (BP1 and BP2), designed to verify different computational methods in solving a mathematically well‐defined, basic faulting problem. We consider a 2D antiplane problem, with a 1D planar vertical strike‐slip fault obeying rate‐and‐state friction, embedded in a 2D homogeneous, linear elastic half‐space. Sequences of quasi‐dynamic earthquakes with periodic occurrences (BP1) or bimodal sizes (BP2) and their interactions with aseismic slip are simulated. The comparison of results from 11 groups using different numerical methods show excellent agreements in long‐term and coseismic fault behavior. In BP1, we found that truncated domain boundaries influence interseismic stressing, earthquake recurrence, and coseismic rupture, and that model agreement is only achieved with sufficiently large domain sizes. In BP2, we found that complexity of fault behavior depends on how well physical length scales related to spontaneous nucleation and rupture propagation are resolved. Poor numerical resolution can result in artificial complexity, impacting simulation results that are of potential interest for characterizing seismic hazard such as earthquake size distributions, moment release, and recurrence times. These results inform the development of more advanced SEAS models, contributing to our further understanding of earthquake system dynamics

Activity of Bdellovibrio Hit Locus Proteins, Bd0108 and Bd0109, Links Type IVa Pilus Extrusion/Retraction Status to Prey-Independent Growth Signalling

Bdellovibrio bacteriovorus are facultatively predatory bacteria that grow within gram-negative prey, using pili to invade their periplasmic niche. They also grow prey-independently on organic nutrients after undergoing a reversible switch. The nature of the growth switching mechanism has been elusive, but several independent reports suggested mutations in the hit (host-interaction) locus on the Bdellovibrio genome were associated with the transition to preyindependent growth. Pili are essential for prey entry by Bdellovibrio and sequence analysis of the hit locus predicted that it was part of a cluster of Type IVb pilus-associated genes, containing bd0108 and bd0109. In this study we have deleted the whole bd0108 gene, which is unique to Bdellovibrio, and compared its phenotype to strains containing spontaneous mutations in bd0108 and the common natural 42 bp deletion variant of bd0108. We find that deletion of the whole bd0108 gene greatly reduced the extrusion of pili, whereas the 42 bp deletion caused greater pilus extrusion than wild-type. The pili isolated from these strains were comprised of the Type IVa pilin protein; PilA. Attempts to similarly delete gene bd0109, which like bd0108 encodes a periplasmic/secreted protein, were not successful, suggesting that it is likely to be essential for Bdellovibrio viability in any growth mode. Bd0109 has a sugar binding YD- repeat motif and an N-terminus with a putative pilin-like fold and was found to interact directly with Bd0108. These results lead us to propose that the Bd0109/Bd0108 interaction regulates pilus production in Bdellovibrio (possibly by interaction with the pilus fibre at the cell wall), and that the presence (and possibly retraction state) of the pilus feeds back to alter the growth state of the Bdellovibrio cell. We further identify a novel small RNA encoded by the hit locus, the transcription of which is altered in different bd0108 mutation background

Mathematical model of the dynamics of psychotherapy

The success of psychotherapy depends on the nature of the therapeutic relationship between a therapist and a client. We use dynamical systems theory to model the dynamics of the emotional interaction between a therapist and client. We determine how the therapeutic endpoint and the dynamics of getting there depend on the parameters of the model. Previously Gottman et al. used a very similar approach (physical-sciences paradigm) for modeling and making predictions about husband–wife relationships. Given that this novel approach shed light on the dyadic interaction between couples, we have applied it to the study of the relationship between therapist and client. The results of our computations provide a new perspective on the therapeutic relationship and a number of useful insights. Our goal is to create a model that is capable of making solid predictions about the dynamics of psychotherapy with the ultimate intention of using it to better train therapists

The INNs and outs of antibody nonproprietary names

An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a –mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclonal antibody therapeutics are categorized and adapts the definitions to new technologies. However, rapid progress in antibody technologies has blurred the boundaries between existing antibody categories and created a burgeoning array of new antibody formats. Thus, revising the INN system for antibodies is akin to aiming for a rapidly moving target. The WHO recently revised INN definitions for antibodies now to be based on amino acid sequence identity. These new definitions, however, are critically flawed as they are ambiguous and go against decades of scientific literature. A key concern is the imposition of an arbitrary threshold for identity against human germline antibody variable region sequences. This leads to inconsistent classification of somatically mutated human antibodies, humanized antibodies as well as antibodies derived from semi-synthetic/synthetic libraries and transgenic animals. Such sequence-based classification implies clear functional distinction between categories (e.g., immunogenicity). However, there is no scientific evidence to support this. Dialog between the WHO INN Expert Group and key stakeholders is needed to develop a new INN system for antibodies and to avoid confusion and miscommunication between researchers and clinicians prescribing antibodies

An atlas of genetic scores to predict multi-omic traits

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics. Here we examine a large cohort (the INTERVAL study; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores

Protection from annual flooding is correlated with increased cholera prevalence in Bangladesh: a zero-inflated regression analysis

<p>Abstract</p> <p>Background</p> <p>Alteration of natural or historical aquatic flows can have unintended consequences for regions where waterborne diseases are endemic and where the epidemiologic implications of such change are poorly understood. The implementation of flood protection measures for a portion of an intensely monitored population in Matlab, Bangladesh, allows us to examine whether cholera outcomes respond positively or negatively to measures designed to control river flooding.</p> <p>Methods</p> <p>Using a zero inflated negative binomial model, we examine how selected covariates can simultaneously account for household clusters reporting no cholera from those with positive counts as well as distinguishing residential areas with low counts from areas with high cholera counts. Our goal is to examine how residence within or outside a flood protected area interacts with the probability of cholera presence and the effect of flood protection on the magnitude of cholera prevalence.</p> <p>Results</p> <p>In Matlab, living in a household that is protected from annual monsoon flooding appears to have no significant effect on whether the household experiences cholera, net of other covariates. However, counter-intuitively, among households where cholera is reported, living within the flood protected region significantly increases the number of cholera cases.</p> <p>Conclusions</p> <p>The construction of dams or other water impoundment strategies for economic or social motives can have profound and unanticipated consequences for waterborne disease. Our results indicate that the construction of a flood control structure in rural Bangladesh is correlated with an increase in cholera cases for residents protected from annual monsoon flooding. Such a finding requires attention from both the health community and from governments and non-governmental organizations involved in ongoing water management schemes.</p