Large-Scale Parameter Estimation for Crystal Structure Prediction. Part 1: Dataset, Methodology, and Implementation.

Crystal structure prediction (CSP) seeks to identify all thermodynamically accessible solid forms of a given compound and, crucially, to establish the relative thermodynamic stability between different polymorphs. The conventional hierarchical CSP workflow suggests that no single energy model can fulfill the needs of all stages in the workflow, and energy models across a spectrum of fidelities and computational costs are required. Hybrid /empirical force-field (HAIEFF) models have demonstrated a good balance of these two factors, but the force-field component presents a major bottleneck for model accuracy.

The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

Prospective Implementation and Early Outcomes of a Risk-stratified Prostate Cancer Active Surveillance Follow-up Protocol.

Background: Active surveillance (AS) is a major management option for men with early prostate cancer. Current guidelines however advocate identical AS follow-up for all without considering different disease trajectories. We previously proposed a pragmatic three-tier STRATified CANcer Surveillance (STRATCANS) follow-up strategy based on different progression risks from clinic-pathological and imaging features.

Development and External Validation of the STRATified CANcer Surveillance (STRATCANS) Multivariable Model for Predicting Progression in Men with Newly Diagnosed Prostate Cancer Starting Active Surveillance.

For men with newly diagnosed prostate cancer, we aimed to develop and validate a model to predict the risk of progression on active surveillance (AS), which could inform more personalised AS strategies. In total, 883 men from 3 European centres were used for model development and internal validation, and 151 men from a fourth European centre were used for external validation. Men with Cambridge Prognostic Group (CPG) 1-2 disease at diagnosis were eligible.

Synthetic Biology Medicine and Bacteria-Based Cancer Therapeutics.

Spontaneous tumor regression following bacterial infection has been observed for hundreds of years. These observations along with anecdotal medical findings in 1890s led to the development of Coley's "toxins," consisting of killed Streptococcus pyogenes and Serratia marcescens bacteria, as the first cancer immunotherapy. The use of this approach, however, was not widely accepted at the time especially after the introduction of radiation therapy as a treatment for cancer in the early 1900s.

Applying the Crystalline Sponge Method to Agrochemicals: Obtaining X-ray Structures of the Fungicide Metalaxyl-M and Herbicide -Metolachlor.

The crystalline sponge method is a technique that provides the ability to elucidate the absolute structure of noncrystalline or hard to crystallize compounds through single-crystal X-ray diffraction by removing the need to obtain crystals of the target compound. In this study the crystalline sponges {[(ZnX)(2,4,6-tris(4-pyridyl)-1,3,5-trazine)].(solvent)} (X = I, Br) were used to obtain X-ray structures of the agrochemical active ingredients metalaxyl-M and S-metolachlor.

Differential patterns of disease and injury in Mozambique: New perspectives from a pragmatic, multicenter, surveillance study of 7809 emergency presentations.

Background: There is a paucity of primary data to understand the overall pattern of disease and injuries as well as related health-service utilization in resource-poor countries in Africa.

Objective: To generate reliable and robust data describing the pattern of emergency presentations attributable to communicable disease (CD), non-communicable disease (NCD) and injuries in three different regions of Mozambique.

Methods: We undertook a pragmatic, prospective, multicentre surveillance study of individuals (all ages) presenting to the emergency departments of three hospitals in Southern (Maputo), Central (Beira) and Northern (Nampula) Mozambique.

Winter Peaks in Heart Failure: An Inevitable or Preventable Consequence of Seasonal Vulnerability?

Climate change is a major contributor to annual winter peaks in cardiovascular events across the globe. However, given the paradoxical observation that cardiovascular seasonality is observed in relatively mild as well as cold climates, global warming may not be as positive for the syndrome of heart failure (HF) as some predict. In this article, we present our Model of Seasonal Flexibility to explain the spectrum of individual responses to climatic conditions.

Pattern and Outcome of Heart Failure-Related Hospitalization Over 5 Years in a Remote Australian Population: A Retrospective Administrative Data Cohort of 617 Indigenous and non-Indigenous Cases.

Objective: The aim of this work was to understand the pattern and outcomes for heart failure (HF)-related hospitalization among Indigenous and non-Indigenous patients living in Central Australia.

Methods And Results: A retrospective analysis of administrative data for patients presenting with a primary or secondary diagnosis of HF to Central Australia's Alice Springs Hospital during 2008-2012 was performed. The population rate of admission and subsequent outcomes (including mortality and readmission) during the 5-year study period were examined.

Seasonal variations in cardiovascular disease.

Cardiovascular disease (CVD) follows a seasonal pattern in many populations. Broadly defined winter peaks and clusters of all subtypes of CVD after 'cold snaps' are consistently described, with corollary peaks linked to heat waves. Individuals living in milder climates might be more vulnerable to seasonality.

Cardiovascular disease in Africa: epidemiological profile and challenges.

From a global perspective, the large and diverse African population is disproportionately affected by cardiovascular disease (CVD). The historical balance between communicable and noncommunicable pathways to CVD in different African regions is dependent on external factors over the life course and at a societal level. The future risk of noncommunicable forms of CVD (predominantly driven by increased rates of hypertension, smoking, and obesity) is a growing public health concern.

The causes, treatment, and outcome of pulmonary hypertension in Africa: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) Registry.

Background: Epidemiology, aetiology, management and outcome data for various forms of pulmonary hypertension (PH) in Africa are scarce.

Methods: A prospective, multinational cohort registry of 220 consecutive patients (97% of African descent) from 9 specialist centres in 4 African countries. The antecedents, characteristics and management of newly diagnosed PH plus 6-month survival were studied.

Establishing a pragmatic framework to optimise health outcomes in heart failure and multimorbidity (ARISE-HF): A multidisciplinary position statement.

Background: Multimorbidity in heart failure (HF), defined as HF of any aetiology and multiple concurrent conditions that require active management, represents an emerging problem within the ageing HF patient population worldwide.

Methods: To inform this position paper, we performed: 1) an initial review of the literature identifying the ten most common conditions, other than hypertension and ischaemic heart disease, complicating the management of HF (anaemia, arrhythmias, cognitive dysfunction, depression, diabetes, musculoskeletal disorders, renal dysfunction, respiratory disease, sleep disorders and thyroid disease) and then 2) a review of the published literature describing the association between HF with each of the ten conditions. From these data we describe a clinical framework, comprising five key steps, to potentially improve historically poor health outcomes in this patient population.

Iron fluorophosphates.

18 new iron fluorophosphates and a chlorofluorophosphate have been synthesised hydrothermally in a fluoride-rich medium, using FeF2, FeF3, Fe, HPF6. HCl, monovalent metal fluorides as reactants and amines as templating agents. Products have been fully structurally characterised using single crystal X-ray diffraction, and the stability of some compounds investigated using thermogravimetric analysis.

Non-medical use of prescription opioids and prescription opioid-related harms: why so markedly higher in North America compared to the rest of the world?

Aims: This paper aims to identify possible system-level factors contributing to the marked differences in the levels of non-medical prescription opioid use (NMPOU) and prescription opioid (PO)-related harms in North America (i.e. the United States and Canada) compared to other global regions.

Ionizing radiation induces stemness in cancer cells.

The cancer stem cell (CSC) model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies.

Human papillomavirus type 8 interferes with a novel C/EBPβ-mediated mechanism of keratinocyte CCL20 chemokine expression and Langerhans cell migration.

Infection with genus beta human papillomaviruses (HPV) is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and 8 in patients with epidermodysplasia verruciformis (EV), a genetic skin disease. So far, it has been unknown how these viruses overcome cutaneous immune control allowing their persistence in lesional epidermis of these patients.

Induction of cancer cell stemness by chemotherapy.

Recent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anticancer therapies.

Targeting cancer gene therapy with magnetic nanoparticles.

Recent advances in cancer genomics have opened up unlimited potential for treating cancer by directly targeting culprit genes. However, novel delivery methods are needed in order for this potential to be translated into clinically viable treatments for patients. Magnetic nanoparticle technology offers the potential to achieve selective and efficient delivery of therapeutic genes by using external magnetic fields, and also allows simultaneous imaging to monitor the delivery in vivo.

Spatial inhomogeneity of anions in ambient particulate matter collected on air filters: determination using a drift-corrected ion chromatography technique.

The spatial inhomogeneity of anions in ambient particulate matter collected on filters has been investigated using two different sub-sampling techniques and with analysis by a drift-corrected ion chromatography technique. The results highlight the inhomogeneity in anion mass along the radius of the sampled filter, in agreement with analogous studies on metals in PM, and also, more surprisingly, significant random differences between sub-samples based on filter sectors. Implications for the sub-sampling of filters for the purposes of performing multiple analyses are discussed.

Optimised determinations of water in ethanol by encoded photometric near-infrared spectroscopy: a special case of sequential standard addition calibration.

A special limiting case of sequential standard addition calibration (S-SAC) has been applied to measurement of the water content of ethanol using encoded photometric near infrared spectroscopy. The method has shown good comparability with certified reference materials and to measurements made by Karl Fischer titration. The technique is quick and easy to use and should have application in high throughput and process measurement, for instance in biofuels analysis at port-of-entry or in bio-refineries.