The experimental degradation of archaeological human bone by anaerobic bacteria and the implications for recovery of ancient DNA

DNA recovery from human bone has been key to the developing science and technology of ancient DNA studies. The recovery of macromolecules from bone however, does not correlate well with recognisable parameters of preservation and predicting DNA recovery rates from ancient bone can be very difficult. The extent of degradation of buried bones often depends on environmental taphonomy and can vary from virtually none to complete and rapid destruction. Although soil or related microbes are undoubtedly responsible for the majority of this structural degradation over time, exceptionally little is known of the mechanisms or specific bacteria involved. Fungi were previously thought to be responsible for destructive processes (tunnelling) within bone but over the last 30 years the role of bacteria has been increasingly recognised. Our aim was to develop a less complex in vitro model of the destructive effects of microbes on bone which might allow a better understanding of the recovery of mitochondrial or pathogen DNA over time

Chemoresistant MyoD+/Nog+ cells restore tumor heterogeneity in rhabdomyosarcoma following initial chemotherapy

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. RMS rarely occurs in adults, but the outcome is significantly worse. Most adult patients with advanced RMS die because their cancer exhibits or develops resistance to available therapies. Chemotherapy treatment for RMS includes Doxorubicin, a DNA intercalating agent and topoisomerase II inhibitor, and Vincristine, a mitosis inhibitor. Histologically, RMS is classified into two main subtypes, embryonal (ERMS) and alveolar (ARMS). ARMS tumors typically harbor chromosomal translocations resulting in the expression of PAX3- or PAX7-FOXO1 fusion proteins. ERMS tumors exhibit a much wider range of genetic abnormalities. The fact that RMS of the same subtype may have significant difference in clinical behavior has been well recognized. Previously, we have shown that RMS cell lines propagated in vitro are heterogeneous with respect to expression of Myoblast determination protein 1 (MyoD1) and Noggin (Nog). Importantly, MyoD+/Nog+ cells have shown higher levels of chemoresistance to Vincristine and Doxorubicin than MyoD negative cells in part to upregulation of anti-apoptotic genes Gli-1 and BcL2 (Dawson et al 2020)

The snakes and ladders of legal participation: litigants in person and the right to a fair trial under Article 6 of the European Convention on Human Rights

This article reviews the right to a fair trial under Article 6 of the European Convention on Human Rights for litigants in person (LIPs). LIPs operate in a system that was not designed for them and so challenge the norm of fully represented parties that the system has evolved to expect, creating potential risks for their Article 6 rights. The jurisprudence on Article 6 reveals the centrality of effective participation as a requirement for fulfilling the right to a fair trial. The article views the jurisprudential interpretation against original and significant empirical research data on how LIPs participate in civil and family court processes. It applies a conceptual analysis of legal participation to consider what might constitute effective participation in court proceedings and, through the empirical evidence, categorizes the intellectual, practical, emotional, and attitudinal barriers that LIPs face in their legal proceedings, which can constitute risks to their rights under Article 6

Establishment of an in vivo Streptozotocin-Induced Type 1 Diabetes Model Recapitulating Early Brain and Retinal Fibrosis

INTRODUCTION: Diabetes has risen to one of the top American public health concerns. The hyperglycemic state of chronic diabetes leads to microvascular and macrovascular changes that predispose patients to delayed wound healing and organ fibrosis. The validation of models to specifically detect early, quantifiable fibrotic changes seen in the diabetic state is of fundamental importance for understanding the diabetic pathophysiology and exploring earlier management options. Here, we investigated if we could detect early signs of internal fibrosis in a streptozotocin (STZ) diabetic mouse model by quantifying α-SMA expression in various organs using flow cytometry. METHODS: We used a low-dose STZ-induced T1DM model. T1DM was confirmed via sustained hyperglycemia (\u3e250mg/dl) over 8-10 weeks. Delayed healing of full thickness wounds was confirmed by tracking wound healing progression over two weeks. Wounded and unwounded skin samples were analyzed histologically to quantify collagen deposition as a sign of fibrosis. Organ fibrosis was assessed in a semi-high-throughput manner using flow cytometry to quantify the percentage of alpha-Smooth Muscle Actin (α-SMA) positive cells in diabetic versus normoglycemic controls. RESULTS: Combining STZ with post-injection glucose treatment yielded highly efficient 100% pathogenesis with 100% survival. Diabetic mice showed signs of hyperglycemia, polyuria, and delayed wound healing. Histological analysis indicated a greater increase in epidermal height and lower levels of collagen deposition in diabetic wounds. After 10-12 weeks of hyperglycemia, we observed elevated α-SMA in brain and retinal tissues. DISCUSSION: The STZ model has previously presented cumbersome, costly, and time-intensive limitations for the study of diabetic complications. Here we tested a quantitative method for detecting early signs of fibrosis using flow cytometry. The higher percentage of α-SMA positive cells in retinal and brain tissue of diabetic mice suggests fibrosis of these tissues. We argue that this is a suitable method to study early diabetic complications

Self administered cognitive screening test (TYM) for detection of Alzheimer’s disease: cross sectional study

Objective To evaluate a cognitive test, the TYM (“test your memory”), in the detection of Alzheimer’s disease

Nitric Oxide and Oxygen Air-Contamination Effects on Extinction Limits of Non-Premixed Hydrocarbon-Air Flames for a HIFiRE Scramjet

Unique nitric oxide (NO) and oxygen air-contamination effects on the extinction Flame Strength (FS) of non-premixed hydrocarbon (HC) vs. air flames are characterized for 7 gaseous HCs, using a new idealized 9.3 mm straight-tube Opposed Jet Burner (OJB) at 1 atm. FS represents a laminar strain-induced extinction limit based on cross-section-average air jet velocity, Uair, that sustains combustion of a counter jet of gaseous fuel just before extinction. Besides ethane, propane, butane, and propylene, the HCs include ethylene, methane, and a 64 mole-% ethylene / 36 % methane mixture, the writer s previously recommended gaseous surrogate fuel for HIFiRE scramjet tests. The HC vs. clean air part of the work is an extension of a May 2008 JANNAF paper that characterized surrogates for the HIFiRE project that should mimic the flameholding of reformed (thermally- or catalytically-cracked) endothermic JP-like fuels. The new FS data for 7 HCs vs. clean air are thus consolidated with the previously validated data, normalized to absolute (local) axial-input strain rates, and co-plotted on a dual kinetically dominated reactivity scale. Excellent agreement with the prior data is obtained for all 7 fuels. Detailed comparisons are also made with recently published (Univ. Va) numerical results for ethylene extinction. A 2009-revised ethylene kinetic model (Univ. Southern Cal) led to predicted limits within approx. 5 % (compared to 45 %, earlier) of this writer s 2008 (and present) ethylene FSs, and also with recent independent data (Univ. Va) obtained on a new OJB system. These +/- 5 % agreements, and a hoped-for "near-identically-performing" reduced kinetics model, would greatly enhance the capability for accurate numerical simulations of surrogate HC flameholding in scramjets. The measured air-contamination effects on normalized FS extinction limits are projected to assess ongoing Arc-Heater-induced "facility test effects" of NO production (e.g., 3 mole-%) and resultant oxygen depletion (from 21 to 19.5 %), for testing the "64/36" surrogate fuel in Langley s Arc-Heated Scramjet Test Facility for HIFiRE engine designs. The FS results show a generally small (< 4 %) "nitric oxide enhancement" effect, relative to clean air, for up to 3 % NO (freestream Mach number up to 7 in Arc Jet testing). However, a progressively large "oxygendeficiency weakening" effect develops. For 3 % NO, a net weakening of 26 % in FS is derived for the "64/36" fuel vs. air. The corresponding net weakening for pure ethylene is 20 %. A number of practical recommendations regarding facility test effects are offered

Developing new approaches to measuring NHS outputs and productivity

The Centre for Health Economics and National Institute of Economic and Social Research have recently completed a project funded by the Department of Health to improve measurement of the productivity of the NHS. The researchers have suggested better ways of measuring both outputs and inputs to improve estimates of productivity growth. Past estimates of NHS output growth have not taken account of changes in quality. The CHE/NIESR team conclude that the routine collection of health outcome data on patients is vital to measure NHS quality. They also propose making better use of existing data to quality adjust output indices to capture improvements in hospital survival rates and reductions in waiting times. With these limited adjustments the team estimate that annual NHS output growth averaged 3.79% between 1998/99 and 2003/04.The research team has also developed improved ways of measuring NHS inputs, particularly by drawing on better information about how many people are employed in the NHS and by recognising that staff are becoming increasingly better qualified. There have been substantial increases in staffing levels, pharmaceutical use and investment in equipment and buildings since 1998/99. The net effect of this growth in both outputs and inputs is that, according to the research team’s estimates, NHS productivity declined by about 1.59% a year since 1998/99. This is not out of line with estimates of growth rates in other UK and US service sectors, including insurance and business services. Nor is it surprising that recent years have seen negative growth in the NHS. There are at least two reasons. First, there has been an unprecedented increase in NHS expenditure. The NHS has had to employ more staff to meet the requirements of the European Working Time Directive and hospital consultants and general practitioners, in particular, have benefited from new pay awards.Second, the NHS collects very little information about what actually happens to patients as a result of their contact with the health service. Until there is routine collection of health outcomes data, measurement of the quality of NHS output will remain partial and productivity growth is likely to be underestimated.