Identification of senescence and death in Emiliania huxleyi and Thalassiosira pseudonana: Cell staining, chlorophyll alterations, and dimethylsulfoniopropionate (DMSP) metabolism

We measured membrane permeability, hydrolytic enzyme, and caspase-like activities using fluorescent cell stains to document changes caused by nutrient exhaustion in the coccolithophore Emiliania huxleyi and the diatom Thalassiosira pseudonana, during batch-culture nutrient limitation. We related these changes to cell death, pigment alteration, and concentrations of dimethylsulfide (DMS) and dimethylsulfoniopropionate (DMSP) to assess the transformation of these compounds as cell physiological condition changes. E. huxleyi persisted for 1 month in stationary phase; in contrast, T. pseudonana cells rapidly declined within 10 d of nutrient depletion. T. pseudonana progressively lost membrane integrity and the ability to metabolize 5-chloromethylfluorescein diacetate (CMFDA; hydrolytic activity), whereas E. huxleyi developed two distinct CMFDA populations and retained membrane integrity (SYTOX Green). Caspase-like activity appeared higher in E. huxleyi than in T. pseudonana during the post-growth phase, despite a lack of apparent mortality and cell lysis. Photosynthetic pigment degradation and transformation occurred in both species after growth; chlorophyll a (Chl a) degradation was characterized by an increase in the ratio of methoxy Chl a : Chl a in T. pseudonana but not in E. huxleyi, and the increase in this ratio preceded loss of membrane integrity. Total DMSP declined in T. pseudonana during cell death and DMS increased. In contrast, and in the absence of cell death, total DMSP and DMS increased in E. huxleyi. Our data show a novel chlorophyll alteration product associated with T. pseudonana death, suggesting a promising approach to discriminate nonviable cells in nature

Cardiac rehabilitation in rural and remote areas of North Queensland: how well are we doing?

Objective: To address access to cardiac rehabilitation (CR) for people in R&R areas, this research aimed to investigate: (1) post discharge systems and support for people returning home from hospital following treatment for heart disease (HD). (2) propose changes to improve access to CR in R&R areas of NQ. Setting: Four focus communities in R&R areas of NQ. Participants: Focus communities’ health staff (resident/visiting) (57), community leaders (10) and community residents (44), discharged from hospital in past 5 years following treatment for heart disease (purposeful sampling). Design: A qualitative descriptive case study, with data collection via semi-structured interviews. Inductive/deductive thematic analysis was used to identify primary and secondary themes. Health service audit of selected communities. Results: Health services in the focus communities included multipurpose health services, and primary health care centres staffed by resident and visiting staff that included nurses, Aboriginal and Torres Strait Islander Health Workers, medical officers, and allied health professionals. Post-discharge health care for people with HD was predominantly clinical. Barriers to CR included low referrals to community-based health professions by discharging hospitals; poorly defined referral pathways; lack of guidelines; inadequate understanding of holistic, multidisciplinary CR by health staff, community participants and leaders; limited centre-based CR services; lack of awareness, or acceptance of telephone support services. Conclusion: To address barriers identified for CR in R&R areas, health care systems’ revision, including development of referral pathways to local health professionals, CR guidelines and in-service education, is required to developing a model of care that focuses on self-management and education: Heart: Road to Health

Cardiac rehabilitation services for people in rural and remote areas: an integrative literature review

Introduction: Morbidity and mortality from heart disease continues to be high in Australia with cardiac rehabilitation (CR) recognised as best practice for people with heart disease. CR is known to reduce mortality, reoccurrence of heart disease, hospital readmissions and costs, and to improve quality of life. Australian Aboriginal and Torres Strait Islanders (Australian First Peoples or Indigenous peoples) have a greater need for CR due to their higher burden of disease. However, CR referral, access and attendance remain low for all people who live in rural and remote areas. The aim of this integrative review was to identify barriers, enablers and pathways to CR for adults living independently in rural and remote areas of high-income countries, including Australia. Methods: Studies were identified through five online data bases, plus reference lists of the selected studies. The studies focused on barriers and enablers of CR for adults in rural and remote areas of Australia and other high-income countries, in English peer reviewed journals (2007-2016). A mix of qualitative, quantitative and mixed method studies were reviewed through a modified Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA), followed by a critical review and thematic analysis. Results: Sixteen studies were selected: seven qualitative, four quantitative and five mixed method. Five themes that influence CR attendance were identified: referral, health services pathways and planning; cultural and geographic factors necessitating alternative and flexible programs; professional roles and influence; knowing, valuing, and psychosocial factors; and financial costs - personal and health services. Factors identified that impact on referral and access to CR were hospital inpatient education programs on heart disease and risk factors; discharge processes including CR eligibility criteria and referral to ensure continuum and transition of care; need for improved accessibility of services, both geographically and through alternative programs, including home based with IT and/or telephone support Also, the need to ensure that health professionals understand, value and support CR; the impact of mental health, coping with change and competing priorities; costs including travel, medications and health professional consultations; as well as low levels of involvement of Australian First Peoples in their own care and poor cultural understanding by non-Australian First Peoples staff all negatively impact on CR access and attendance. Conclusion: This study found weak systems with low referral rates and poor access to CR in rural and remote areas. Underlying factors include lack of health professional and public support, often based on poor perception of benefits of CR, compounded by scarce and inflexible services. Low levels of involvement of Australian First Peoples, as well as a lack of cultural understanding by non-Australian First Peoples staff, is evident Overall, the findings demonstrate the need for improved models of referral and access, greater flexibility of programs and professional roles, with management support Further, increased education and involvement of Australian First Peoples, including Indigenous health workers taking a lead in their own people's care, supported by improved education and greater cultural awareness of non Australian First Peoples staff, is required

Large Scale Parallelization in Stochastic Coupled Cluster

Coupled cluster theory is a vital cornerstone of electronic structure theory and is being applied to ever-larger systems. Stochastic approaches to quantum chemistry have grown in importance and offer compelling advantages over traditional deterministic algorithms in terms of computational demands, theoretical flexibility or lower scaling with system size. We present a highly parallelizable algorithm of the coupled cluster Monte Carlo method involving sampling of clusters of excitors over multiple time steps. The behaviour of the algorithm is investigated on the uniform electron gas and the water dimer at CCSD, CCSDT and CCSDTQ levels. We also describe two improvements to the original sampling algorithm, full non-composite and multi-spawn sampling. A stochastic approach to coupled cluster results in an efficient and scalable implementation at arbitrary truncation levels in the coupled cluster expansion.Thomas Young Centre TYC-101, EPSRC Centre for Doctoral Training in Computational Methods for Materials Science EP/L015552/1, Cambridge Philosophical Society, EPSRC, CHESS, Royal Society University Research Fellowship UF110161 and UF160398, ARCHER UK National Supercomputing Service (http://www.archer.ac.uk) grant e507, UK Research Data Facility (http://www.archer.ac.uk/documentation/rdf-guide) grant e507, resources provided by the Cambridge Service for Data Driven Discovery (CSD3) operated by the University of Cambridge Research Computing Service (http://www.csd3.cam.ac.uk/), provided by Dell EMC and Intel using Tier-2 funding from the Engineering and Physical Sci- ences Research Council (capital grant EP/P020259/1), and DiRAC funding from the Science and Technology Facilities Council (www.dirac.ac.uk

The HANDE-QMC Project: Open-Source Stochastic Quantum Chemistry from the Ground State Up.

Building on the success of Quantum Monte Carlo techniques such as diffusion Monte Carlo, alternative stochastic approaches to solve electronic structure problems have emerged over the past decade. The full configuration interaction quantum Monte Carlo (FCIQMC) method allows one to systematically approach the exact solution of such problems, for cases where very high accuracy is desired. The introduction of FCIQMC has subsequently led to the development of coupled cluster Monte Carlo (CCMC) and density matrix quantum Monte Carlo (DMQMC), allowing stochastic sampling of the coupled cluster wave function and the exact thermal density matrix, respectively. In this Article, we describe the HANDE-QMC code, an open-source implementation of FCIQMC, CCMC and DMQMC, including initiator and semistochastic adaptations. We describe our code and demonstrate its use on three example systems; a molecule (nitric oxide), a model solid (the uniform electron gas), and a real solid (diamond). An illustrative tutorial is also included

Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer

Purpose Nelfinavir, a PI3-kinase pathway inhibitor, is a radiosensitizer which increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. Patients and Methods Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1250 mg bd) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pre-treatment, after 7 days of nelfinavir and prior to last fraction of RT. Biopsies taken pre-treatment and 7 days after the last fraction of RT were analysed for tumor cell density (TCD). Results There were 3 drug-related grade 3 adverse events: diarrhea, rash, lymphopenia. On DCE-MRI, there was a mean 42% increase in median Ktrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P=0.01). Overall, 5/9 evaluable patients exhibited good tumor regression on MRI assessed by Tumor Regression Grade (mrTRG). Conclusions This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow

Modeling sustainability : Population, inequality, consumption, and bidirectional coupling of the Earth and human systems

Over the last two centuries, the impact of the Human System has grown dramatically, becoming strongly dominant within the Earth System in many different ways. Consumption, inequality, and population have increased extremely fast, especially since about 1950, threatening to overwhelm the many critical functions and ecosystems of the Earth System. Changes in the Earth System, in turn, have important feedback effects on the Human System, with costly and potentially serious consequences. However, current models do not incorporate these critical feedbacks. We argue that in order to understand the dynamics of either system, Earth SystemModels must be coupled with Human SystemModels through bidirectional couplings representing the positive, negative, and delayed feedbacks that exist in the real systems. In particular, key Human System variables, such as demographics, inequality, economic growth, and migration, are not coupled with the Earth System but are instead driven by exogenous estimates, such as United Nations population projections.This makes current models likely to miss important feedbacks in the real Earth-Human system, especially those that may result in unexpected or counterintuitive outcomes, and thus requiring different policy interventions from current models.The importance and imminence of sustainability challenges, the dominant role of the Human System in the Earth System, and the essential roles the Earth System plays for the Human System, all call for collaboration of natural scientists, social scientists, and engineers in multidisciplinary research and modeling to develop coupled Earth-Human system models for devising effective science-based policies and measures to benefit current and future generations

Abundance of a chlorophyll a precursor and the oxidation product hydroxychlorophyll a during seasonal phytoplankton community progression in the Western English Channel

This study presents the first in-situ measurements of the chlorophyll a oxidation product, hydroxychlorophyll a as well as the chlorophyll a precursor, chlorophyll aP276 conducted over an annual cycle. Chlorophyll a oxidation products, such as hydroxychlorophyll a may be associated with the decline of algal populations and can act as an initial step in the degradation of chlorophyll a into products which can be found in the geochemical record, important for studying past climate change events. Here, hydroxychlorophyll a and chlorophyll aP276 were measured at the long-term monitoring station L4, Western Channel Observatory (UK, www.westernchannelobservatory.org) over an annual cycle (2012). Weekly measurements of phytoplankton species composition and abundance enabled detailed analysis of possible sources of hydroxychlorophyll a. Dinoflagellates, 2 diatom species, the prymnesiophyte Phaeocystis spp. and the coccolithophorid Emiliania huxleyi were all associated with hydroxychlorophyll a occurrence. However, during alternate peaks in abundance of the diatoms, no association with hydroxychlorophyll a occurred, indicating that the oxidation of chlorophyll a was dependant not only on species but also on additional factors such as the mode of mortality, growth limiting factor (i.e. nutrient concentration) or phenotypic plasticity. Surface sediment samples contained 10 times more hydroxychlorophyll a (relative to chlorophyll a) than pelagic particulate samples, indicating that more chlorophyll a oxidation occurred during sedimentation or at the sediment-water interface, than in the pelagic environment. In addition, chlorophyll aP276 correlated with chl-a concentration, thus supporting its assignment as a chl-a precursor

The Effectiveness of Non-pyrethroid Insecticide-treated Durable Wall Lining to Control Malaria in Rural Tanzania: Study Protocol for a Two-armed Cluster Randomized Trial.

Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts