Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis.

Background A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS. Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results There was a significant (p<0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum. Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively.  The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001). The serum lactate dehydrogenase activity was also highly significantly raised (p<10-12) in patients with secondary progressive multiple sclerosis. Conclusions An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe2+) is chelated by haemoglobin

Advancing the field of health systems research synthesis.

Those planning, managing and working in health systems worldwide routinely need to make decisions regarding strategies to improve health care and promote equity. Systematic reviews of different kinds can be of great help to these decision-makers, providing actionable evidence at every step in the decision-making process. Although there is growing recognition of the importance of systematic reviews to inform both policy decisions and produce guidance for health systems, a number of important methodological and evidence uptake challenges remain and better coordination of existing initiatives is needed. The Alliance for Health Policy and Systems Research, housed within the World Health Organization, convened an Advisory Group on Health Systems Research (HSR) Synthesis to bring together different stakeholders interested in HSR synthesis and its use in decision-making processes. We describe the rationale of the Advisory Group and the six areas of its work and reflects on its role in advancing the field of HSR synthesis. We argue in favour of greater cross-institutional collaborations, as well as capacity strengthening in low- and middle-income countries, to advance the science and practice of health systems research synthesis. We advocate for the integration of quasi-experimental study designs in reviews of effectiveness of health systems intervention and reforms. The Advisory Group also recommends adopting priority-setting approaches for HSR synthesis and increasing the use of findings from systematic reviews in health policy and decision-making

The significance and expectations of HIV cure research among people living with HIV in Australia.

Most people living with HIV (PLHIV) with reliable access to antiretroviral treatment (ART) have a life expectancy similar to uninfected populations. Despite this, HIV can negatively affect their social and psychological wellbeing. This study aimed to enhance understanding of the expectations PLHIV hold for HIV cure research and the implications this has for HIV cure research trials. We interviewed 20 Australian PLHIV about their expectations for HIV cure research outcomes and the impact a potential cure for HIV may have on their everyday lives. Data were analysed thematically, using both inductive and deductive approaches. The significance of a cure for HIV was expressed by participants as something that would offer relief from their sense of vigilance or uncertainty about their health into the future. A cure was also defined in social terms, as alleviation from worry about potential for onward HIV transmission, concerns for friends and family, and the negative impact of HIV-related stigma. Participants did not consider sustained medication-free viral suppression (or remission) as a cure for HIV because this did not offer certainty in remaining virus free in a way that would alleviate these fears and concerns. A cure was seen as complete elimination of HIV from the body. There is an ethical need to consider the expectations of PLHIV in design of, and recruitment for, HIV cure-related research. The language used to describe HIV cure research should differentiate the long-term aspiration of achieving complete elimination of HIV from the body and possible shorter-term therapeutic advances, such as achieving medication free viral suppression

SUPPORT Tools for evidence-informed health Policymaking (STP) 5: Using research evidence to frame options to address a problem

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Clinical activity in general practice before sarcoma diagnosis: an Australian cohort study

Background Increased time to diagnosis in sarcoma is associated with poor prognosis and patient outcomes. Research is needed to identify whether opportunities to expedite the diagnosis of sarcoma in general practice exist. Aim To examine pre-diagnostic GP clinical activity before sarcoma diagnosis. Design and setting An Australian retrospective cohort study using hospital registry data (Australian Comprehensive Cancer Outcomes and Research Database [ACCORD]) linked to two primary care datasets (Patron and MedicineInsight). Method The frequency of general practice healthcare utilisation events (general practice attendances, prescriptions, blood test, and imaging requests) were compared in 377 patients with soft tissue sarcoma (STS) and 64 patients with bone sarcoma (BS) in the year pre-diagnosis. Poisson regression models were used to calculate monthly incidence rate ratios (IRR) for the 24 months pre-diagnosis and estimate inflection points for when healthcare use started to increase from baseline. Results In the 6 months pre-diagnosis, patients with sarcoma had a median of 3–4 general practice attendances, around one-third had a GP imaging request (33% [n = 21] BS and 36% [n = 134] STS), and approximately one in five had multiple imaging requests (19% [n = 12] BS and 21% [n = 80] STS). GP imaging requests progressively increased up to eight-fold from 6 months before sarcoma diagnosis (IRR 8.43, 95% confidence interval [CI] = 3.92 to 18.15, P<0.001) and general practice attendances increased from 3 months pre-diagnosis. Conclusion Patients with sarcoma have increased GP clinical activity from 6 months pre-diagnosis, indicating a diagnostic window where potential opportunities exist for earlier diagnosis. Interventions to help identify patients and promote appropriate use of imaging and direct specialist centre referrals could improve earlier diagnosis and patient outcomes

SUPPORT Tools for evidence-informed health Policymaking (STP) 7: Finding systematic reviews

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

Thermonuclear Stability of Material Accreting onto a Neutron Star

We present a global linear stability analysis of nuclear fuel accumulating on the surface of an accreting neutron star and we identify the conditions under which thermonuclear bursts are triggered. The analysis reproduces all the recognized regimes of hydrogen and helium bursts, and in addition shows that at high accretion rates, near the limit of stable burning, there is a regime of ``delayed mixed bursts'' which is distinct from the more usual ``prompt mixed bursts.'' In delayed mixed bursts, a large fraction of the fuel is burned stably before the burst is triggered. Bursts thus have longer recurrence times, but at the same time have somewhat smaller fluences. Therefore, the parameter alpha, which measures the ratio of the energy released via accretion to that generated through nuclear reactions in the burst, is up to an order of magnitude larger than for prompt bursts. This increase in alpha near the threshold of stable burning has been seen in observations. We explore a wide range of mass accretion rates, neutron star radii and core temperatures, and calculate a variety of burst properties. From a preliminary comparison with data, we suggest that bursting neutron stars may have hot cores, with T_{core} >~ 10^{7.5} K, consistent with interior cooling via the modified URCA or similar low-efficiency process, rather than T_{core} ~ 10^7 K, as expected for the direct URCA process. There is also an indication that neutron star radii are somewhat small <~ 10 km. Both of these conclusions need to be confirmed by comparing more careful calculations with better data.Comment: 67 pages, 19 figures, final version to appear in The Astrophysical Journal, vol. 599, no. 1, Dec. 10, 200

Variations of Surveillance Practice for Patients with Bone Sarcoma: A Survey of Australian Sarcoma Clinicians

Introduction. After treatment, bone sarcoma patients carry a high chance of relapse and late effects from multimodal therapy. We hypothesize that significant variation in surveillance practice exists between pediatric medical oncology (PO) and nonpediatric medical oncology (NP) sarcoma disciplines. Methods. Australian sarcoma clinicians were approached to do a web based survey that assessed radiologic surveillance (RS) strategies, late toxicity assessment, and posttreatment psychosocial interventions. Results. In total, 51 clinicians responded. No differences were identified in local disease RS. In metastatic disease response assessment, 100% of POs (23/23) and 93% of NPs (24/26) conducted CT chest. However, this was more likely to occur for NPs in the context of a CT chest/abdomen/pelvis (NP: 10/26; PO: 1/23; p=0.006). POs were more likely to use CXR for RS (p=0.006). POs showed more prescriptive intensity in assessment of heart function (p=0.001), hearing (p<0.001), and fertility (p=0.02). POs were more likely to deliver written information for health maintenance/treatment summary (p=0.04). The majority of respondents described enquiring about psychosocial aspects of health (n=33/37, 89%), but a routine formal psychosocial screen was only used by 23% (n=6/26). Conclusion. There is high variability in bone sarcoma surveillance between PO and NP clinicians. Efforts to harmonize approaches would allow early and late effects recognition/intervention and facilitate improved patient care/transition and research

The Significance of Hair for Face Recognition

Hair is a feature of the head that frequently changes in different situations. For this reason much research in the area of face perception has employed stimuli without hair. To investigate the effect of the presence of hair we used faces with and without hair in a recognition task. Participants took part in trials in which the state of the hair either remained consistent (Same) or switched between learning and test (Switch). It was found that in the Same trials performance did not differ for stimuli presented with and without hair. This implies that there is sufficient information in the internal features of the face for optimal performance in this task. It was also found that performance in the Switch trials was substantially lower than in the Same trials. This drop in accuracy when the stimuli were switched suggests that faces are represented in a holistic manner and that manipulation of the hair causes disruption to this, with implications for the interpretation of some previous studies

A comparative genomics multitool for scientific discovery and conservation

A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal-including 131 previously uncharacterized species-from the Zoonomia Project provides data that support biological discovery, medical research and conservation. The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.Peer reviewe