Intracranial Hemorrhage Due to Secondary Hypertension from Intracranial Large Vessel Occlusion

Simultaneous hemorrhagic and ischemic strokes have been previously reported in the literature. Typically, these occur in patients secondary to dialysis, cerebral amyloid angiopathy, or thrombotic thrombocytopenic purpura.1,2,3 However, this is the unique case of a 62-year-old Asian female who presented with a hemorrhagic stroke suspected to be secondary to refractory hypertension from intracranial large vessel atherosclerotic flow limiting stenosis, with rapid subsequent large vessel occlusion and ischemic stroke. Questions arise such as ideal blood pressure parameters for dual management, timeliness of computed tomography angiography imaging in the emergency department for detection of large vessel occlusion during intracranial hemorrhage, and subsequent selection of treatment plan in the dual-lesion patient population

Sustainability and growth: São Paulo

The Global Dialogue on Sustainability, Climate Change and Economic Growth was held in São Paulo in October 2011. It was co-organised by the Brazilian Centre for Analysis and Planning (CEBRAP) and the Institute of Development Studies (IDS). The idea was to bring together practitioners and thinkers to explore through dialogue the key issues relating to sustainability, climate change and economic growth both now and over the next 20 or 30 years. It was a diverse and broad-based gathering that not only included entrepreneurs, directors of philanthropic organisations and researchers but also made a particular effort to include spokespeople from marginalised communities – indigenous and riverine smallholder representatives from the Amazon and Atlantic rainforest regions and a pastoralist representative from Ethiopia – who have often been excluded from conventional debates about sustainability, climate change and economic growth. These conventional debates focus on the biological and scientific aspects of environmental resilience, climate change and conservation, and often overlook indigenous people whose knowledge is key to meeting these challenges but whose livelihoods and wellbeing are threatened by unrestrained economic growth and technological expansion. The key issues for philanthropists identified during the Dialogue were: Recognising diversity and respecting plural perspectives on challenges and opportunities; Facilitating autonomy through hands-on engagement with grassroots initiatives, going beyond short-term project cycles and allowing for local-level learning; Supporting relationships, helping to build networks and broker connections between different levels, sectors and interests; and Addressing power and politics in both forms of knowledge (integrating the social and the biological) and governance and decision-making processes, recognising that democratisation plays a critical role in relation to sustainability, climate change and economic growth.The Rockerfeller Foundatio

Molecular staging individualizing cancer management

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc

The prevalence and topography of spinal cord demyelination in multiple sclerosis: a retrospective study

Spinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. The demyelinated lesion is a cardinal feature. The well-characterised anatomy of the spinal cord and new analytic approaches allows the systematic study of lesion topography and its extent of inflammatory activity unveiling new insights into disease pathogenesis. We studied cervical, thoracic, and lumbar spinal cord tissue from 119 pathologically confirmed multiple sclerosis cases. Immunohistochemistry was used to detect demyelination (PLP) and classify lesional inflammatory activity (CD68). Prevalence and distribution of demyelination, staged by lesion activity, was determined and topographical maps were created to identify patterns of lesion prevalence and distribution using mixed models and permutation-based voxelwise analysis. 460 lesions were observed throughout the spinal cord with 76.5% of cases demonstrating at least 1 lesion. The cervical level was preferentially affected by lesions. 58.3% of lesions were inflammatory with 87.9% of cases harbouring at least 1 inflammatory lesion. Topographically, lesions consistently affected the dorsal and lateral columns with relative sparing of subpial areas in a distribution mirroring the vascular network. The presence of spinal cord lesions and the proportion of active lesions related strongly with clinical disease milestones, including time from onset to wheelchair and onset to death. We demonstrate that spinal cord demyelination is common, highly inflammatory, has a predilection for the cervical level, and relates to clinical disability. The topography of lesions in the dorsal and lateral columns and relative sparing of subpial areas points to a role of the vasculature in lesion pathogenesis, suggesting short-range cell infiltration from the blood and signaling molecules circulating in the perivascular space incite lesion development. These findings challenge the notion that end-stage progressive multiple sclerosis is ‘burnt out’ and an outside-in lesional gradient predominates in the spinal cord. Taken together, this study provides support for long-term targeting of inflammatory demyelination in the spinal cord and nominates vascular dysfunction as a potential target for new therapeutic approaches to limit irreversible disability

Origin of the Amphibian Chytrid Fungus

Histologic evidence indicates southern Africa as the origin of the amphibian chytrid fungus

Rates of glycaemic deterioration in a real-world population with type 2 diabetes

Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on 'time to failure' methods, yet determining a 'coefficient of failure' has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration. Methods: An observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual's observed HbA(1c) measures from the first eligible HbA(1c) after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA(1c) measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution. Results: The mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA(1c) per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA(1c) per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA(1c) per year. Conclusions/interpretation: We have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management

The Extreme Hosts of Extreme Supernovae

We use GALEX ultraviolet (UV) and optical integrated photometry of the hosts of seventeen luminous supernovae (LSNe, having peak M_V < -21) and compare them to a sample of 26,000 galaxies from a cross-match between the SDSS DR4 spectral catalog and GALEX interim release 1.1. We place the LSNe hosts on the galaxy NUV-r versus M_r color magnitude diagram (CMD) with the larger sample to illustrate how extreme they are. The LSN hosts appear to favor low-density regions of the galaxy CMD falling on the blue edge of the blue cloud toward the low luminosity end. From the UV-optical photometry, we estimate the star formation history of the LSN hosts. The hosts have moderately low star formation rates (SFRs) and low stellar masses (M_*) resulting in high specific star formation rates (sSFR). Compared with the larger sample, the LSN hosts occupy low-density regions of a diagram plotting sSFR versus M_* in the area having higher sSFR and lower M_*. This preference for low M_*, high sSFR hosts implies the LSNe are produced by an effect having to do with their local environment. The correlation of mass with metallicity suggests that perhaps wind-driven mass loss is the factor that prevents LSNe from arising in higher-mass, higher-metallicity hosts. The massive progenitors of the LSNe (>100 M_sun), by appearing in low-SFR hosts, are potential tests for theories of the initial mass function that limit the maximum mass of a star based on the SFR.Comment: 8 pages, 3 figures, 2 tables, accepted to ApJ, amended references and updated SN designation

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4(+) enterocytes, microfold-like cells, and IL13RA2(+)IL11(+) inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and coregulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.Peer reviewe