Expression and purification of an active cysteine protease of Haemonchus contortus using Caenorhabditis elegans

A

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders

Counselling in primary care : a systematic review of the evidence

Primary objective: To undertake a systematic review which aimed to locate, appraise and synthesise evidence to obtain a reliable overview of the clinical effectiveness, cost-effectiveness and user perspectives regarding counselling in primary care. Main results: Evidence from 26 studies was presented as a narrative synthesis and demonstrated that counselling is effective in the short term, is as effective as CBT with typical heterogeneous primary care populations and more effective than routine primary care for the treatment of non-specific generic psychological problems, anxiety and depression. Counselling may reduce levels of referrals to psychiatric services, but does not appear to reduce medication, the number of GP consultations or overall costs. Patients are highly satisfied with the counselling they have received in primary care and prefer counselling to medication for depression. Conclusions and implications for future research: This review demonstrates the value of counselling as a valid choice for primary care patients and as a broadly effective therapeutic intervention for a wide range of generic psychological conditions presenting in the primary care setting. More rigorous clinical and cost-effectiveness trials are needed together with surveys of more typical users of primary care services

Traditional Cardiovascular Risk Factors as Predictors of Cardiovascular Events in the U.S. Astronaut Corps

Risk prediction equations from the Framingham Heart Study are commonly used to predict the absolute risk of myocardial infarction (MI) and coronary heart disease (CHD) related death. Predicting CHD-related events in the U.S. astronaut corps presents a monumental challenge, both because astronauts tend to live healthier lifestyles and because of the unique cardiovascular stressors associated with being trained for and participating in space flight. Traditional risk factors may not hold enough predictive power to provide a useful indicator of CHD risk in this unique population. It is important to be able to identify individuals who are at higher risk for CHD-related events so that appropriate preventive care can be provided. This is of special importance when planning long duration missions since the ability to provide advanced cardiac care and perform medical evacuation is limited. The medical regimen of the astronauts follows a strict set of clinical practice guidelines in an effort to ensure the best care. The purpose of this study was to evaluate the utility of the Framingham risk score (FRS), low-density lipoprotein (LDL) and high-density lipoprotein levels, blood pressure, and resting pulse as predictors of CHD-related death and MI in the astronaut corps, using Cox regression. Of these factors, only two, LDL and pulse at selection, were predictive of CHD events (HR(95% CI)=1.12 (1.00-1.25) and HR(95% CI)=1.70 (1.05-2.75) for every 5-unit increase in LDL and pulse, respectively). Since traditional CHD risk factors may lack the specificity to predict such outcomes in astronauts, the development of a new predictive model, using additional measures such as electron-beam computed tomography and carotid intima-media thickness ultrasound, is planned for the future

Palliative care making a difference in rural Uganda, Kenya and Malawi: three rapid evaluation field studies

<p>Abstract</p> <p>Background</p> <p>Many people live and die in pain in Africa. We set out to describe patient, family and local community perspectives on the impact of three community based palliative care interventions in sub-Saharan Africa.</p> <p>Methods</p> <p>Three palliative care programmes in Uganda, Kenya and Malawi were studied using rapid evaluation field techniques in each country, triangulating data from three sources: <b><it>interviews </it></b>with key informants, <b><it>observations </it></b>of clinical encounters and the local health and social care context, and routine data from local <b><it>reports and statistics</it></b>.</p> <p>Results</p> <p>We interviewed 33 patients with advanced illness, 27 family carers, 36 staff, 25 volunteers, and 29 community leaders and observed clinical care of 12 patients. In each site, oral morphine was being used effectively. Patients valued being treated with dignity and respect. Being supported at home reduced physical, emotional and financial burden of travel to, and care at health facilities. Practical support and instruction in feeding and bathing patients facilitated good deaths at home.</p> <p>In each country mobile phones enabled rapid access to clinical and social support networks. Staff and volunteers generally reported that caring for the dying in the face of poverty was stressful, but also rewarding, with resilience fostered by having effective analgesia, and community support networks.</p> <p>Conclusions</p> <p>Programmes were reported to be successful because they integrated symptom control with practical and emotional care, education, and spiritual care. Holistic palliative care can be delivered effectively in the face of poverty, but a public health approach is needed to ensure equitable provision.</p

Thin-layer effects in glaciological seismic amplitude-versus-angle (AVA) analysis: implications for characterising a subglacial till unit, Russell Glacier, West Greenland

Seismic amplitude-versus-angle (AVA) methods are a powerful means of quantifying the physical properties of subglacial material, but serious interpretative errors can arise when AVA is measured over a thinly-layered substrate. A substrate layer with a thickness less than 1/4 of the seismic wavelength, λ, is considered "thin", and reflections from its bounding interfaces superpose and appear in seismic data as a single reflection event. AVA interpretation of subglacial till can be vulnerable to such thin-layer effects, since a lodged (non-deforming) till can be overlain by a thin (metre-scale) cap of dilatant (deforming) till. We assess the potential for misinterpretation by simulating seismic data for a stratified subglacial till unit, with an upper dilatant layer between 0.1–5.0 m thick (λ / 120 to &gt; λ / 4, with &amp;lambda; = 12 m). For dilatant layers less than &amp;lambda; / 6 thick, conventional AVA analysis yields acoustic impedance and Poisson's ratio that indicate contradictory water saturation. A thin-layer interpretation strategy is proposed, that accurately characterises the model properties of the till unit. The method is applied to example seismic AVA data from Russell Glacier, West Greenland, in which characteristics of thin-layer responses are evident. A subglacial till deposit is interpreted, having lodged till (acoustic impedance = 4.26&amp;plusmn;0.59 &amp;times; 10&lt;sup&gt;6&lt;/sup&gt; kg m&lt;sup&gt;−2&lt;/sup&gt; s&lt;sup&gt;&amp;minus;1&lt;/sup&gt;) underlying a water-saturated dilatant till layer (thickness &lt; 2 m, Poisson's ratio ~ 0.5). Since thin-layer considerations offer a greater degree of complexity in an AVA interpretation, and potentially avoid misinterpretations, they are a valuable aspect of quantitative seismic analysis, particularly for characterising till units

Photoinduced suppression of the ferroelectric instability in PbTe

The interactions between electrons and phonons drive a large array of technologically relevant material properties including ferroelectricity, thermoelectricity, and phase-change behaviour. In the case of many group IV-VI, V, and related materials, these interactions are strong and the materials exist near electronic and structural phase transitions. Their close proximity to phase instability produces a fragile balance among the various properties. The prototypical example is PbTe whose incipient ferroelectric behaviour has been associated with large phonon anharmonicity and thermoelectricity. Experimental measurements on PbTe reveal anomalous lattice dynamics, especially in the soft transverse optical phonon branch. This has been interpreted in terms of both giant anharmonicity and local symmetry breaking due to off-centering of the Pb ions. The observed anomalies have prompted renewed theoretical and computational interest, which has in turn revived focus on the extent that electron-phonon interactions drive lattice instabilities in PbTe and related materials. Here, we use Fourier-transform inelastic x-ray scattering (FT-IXS) to show that photo-injection of free carriers stabilizes the paraelectric state. With support from constrained density functional theory (CDFT) calculations, we find that photoexcitation weakens the long-range forces along the cubic direction tied to resonant bonding and incipient ferroelectricity. This demonstrates the importance of electronic states near the band edges in determining the equilibrium structure.Comment: 9 page, 3 figure

What Drives the Expansion of Giant HII Regions?: A Study of Stellar Feedback in 30 Doradus

Observations show that star formation is an inefficient and slow process. This result can be attributed to the injection of energy and momentum by stars that prevents free-fall collapse of molecular clouds. The mechanism of this stellar feedback is debated theoretically: possible sources of pressure include the classical warm HII gas, the hot gas generated by shock-heating from stellar winds and supernovae, direct radiation of stars, and the dust-processed radiation field trapped inside the HII shell. In this paper, we measure observationally the pressures associated with each component listed above across the giant HII region 30 Doradus in the Large Magellanic Cloud. We exploit high-resolution, multi-wavelengh images (radio, infrared, optical, and X-ray) to map these pressures as a function of position. We find that radiation pressure dominates within 75 pc of the central star cluster, R136, while the HII gas pressure dominates at larger radii. By contrast, the dust-processed radiation pressure and hot gas pressure are generally weak and not dynamically important, although the hot gas pressure may have played a more significant role at early times. Based on the low X-ray gas pressures, we demonstrate that the hot gas is only partially confined and must be leaking out the HII shell. Additionally, we consider the implications of a dominant radiation pressure on the early dynamics of 30 Doradus.Comment: 14 pages, 17 figures; ApJ in pres

Correlates of Complete Childhood Vaccination in East African Countries.

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority