tbuckley/cabot-search huggingface dataset:
Outreach education for integration of HIV/AIDS care, antiretroviral treatment, and tuberculosis care in primary care clinics in South Africa: PALSA PLUS pragmatic cluster randomised trial
Authors: M. Zwarenstein, L. R. Fairall, C. Lombard, P. Mayers, A. Bheekie, R. G. English, S. Lewin, M. O. Bachmann, E. Bateman
Journal: BMJ (2011)

<b>Objective</b> To investigate whether PALSA PLUS, an on-site educational outreach programme of non-didactic, case based, iterative clinical education of staff, led by a trainer, can increase access to and comprehensiveness of care for patients with HIV/AIDS. <b>Design </b> Cluster randomised trial. <b>Setting</b> Public primary care clinics offering HIV/AIDS care, antiretroviral treatment (ART), tuberculosis care, and ambulatory primary care in Free State province, South Africa. <b>Participants</b> Fifteen clinics all implementing decentralisation and task shifting were randomised. The clinics cared for 400 000 general primary care patients and 10 136 patients in an HIV/AIDS/ART programme. There were 150 nurses. <b>Intervention</b> On-site outreach education in eight clinics; no such education in seven (control). <b>Main outcome measures</b> Provision of co-trimoxazole prophylaxis among patients referred to the HIV/AIDS/ART programme, and detection of cases of tuberculosis among those in the programme. Proportion of patients in the programme enrolled through general primary care consultations. <b>Results</b> Patients referred to the HIV/AIDS programme through general primary care at intervention clinics were more likely than those at control clinics to receive co-trimoxazole prophylaxis (41%, (2253/5523) <i>v</i> 32% (1340/4210); odds ratio 1.95, 95% confidence interval 1.11 to 3.40), and tuberculosis was more likely to be diagnosed among patients with HIV/AIDS/ART (7% (417/5793) <i>v</i> 6% (245/4343); 1.25, 1.01 to 1.55). Enrolment in the HIV/AIDS and ART programme through HIV testing in general primary care was not significantly increased (53% <i>v</i> 50%; 1.19, 0.51 to 2.77). Secondary outcomes were similar, except for weight gain, which was higher in the intervention group (2.3 kg <i>v</i> 1.9 kg, P&lt;0.001). <b>Conclusion</b> Though outreach education is an effective and feasible strategy for improving comprehensiveness of care and wellbeing of patients with HIV/AIDS, there is no evidence that it increases access to the ART programme. It is now being widely implemented in South Africa. <b>Trial registration</b> Current Controlled Trials ISRCTN 24820584.
P54 Is F-18 FDG PET/CT accurate in detecting nodal disease in patients with suspected lung cancer?
Authors: M Haris, S Leyakathali khan, S Diver, J Hill, M Munavvar, H Ansari
Journal: Thorax (2013)

<h3>Background</h3> Accurate assessment of mediastinal lymph nodes is crucial in determining the management strategies in patients with lung cancer, particularly in those suitable for radical treatment. Positron emission tomography/computed tomography (PET-CT) is currently the best available imaging tool to assess nodal involvement and current guidelines recommend further sampling of PET positive lymph nodes to confirm the diagnosis using image-guided or surgical techniques to achieve the best treatment outcomes. We proceeded to look at the accuracy of (18) F-FDG PET/CT in detecting nodal metastasis in lung cancer. <h3>Methods</h3> Retrospective study of 68 pathologically confirmed metastatic lymph nodes obtained using endobronchial ultrasound (EBUS) guided needle aspiration between Jan 2009 and Jan 2012. All pre-procedure PET/CT images were reviewed by a Consultant Radiologist who was blinded to the EBUS findings and the pathology results. PET standardised uptake value (SUVmax) of the primary lung lesion and suspected lymph nodes was measured. Data was collected from our EBUS database and analysed. <h3>Results</h3> Of the 68 lymph nodes, 24 were subcarinal, 14 right lower paratracheal, 6 left lower paratracheal, 2 upper right paratracheal, 1 right inter-lobar, 10 right hilar and 11 were left hilar. EBUS lymph node size (mm) 18 mean, SD 6 (range 7 34). Mean PET SUVmax of the lymph nodes was 9.1, 6.7 SD (2 34); mean PET SUVmax of the primary tumour (n = 50) was 10.6(7.6 SD). 23 nodes were squamous, 17 nodes adenocarcinoma, 9 small cell, 13 non-small cell (not otherwise specified), 5 extra-thoracic, and 1 neuroendocrine. 52 nodes were positive on PET, 9 were negative and 7 indeterminate. <h3>Conclusion</h3> Our results show that out of the 68 pathologically confirmed lymph nodes 52 were positive on PET/CT with diagnostic accuracy of 76%. SUVmax may be used as a guide to characterise the nodes but not as a confirmatory tool. Despite limitations PET/CT is accurate and it is complemented by image-guided sampling in the lung cancer diagnostic pathway. <h3>References</h3> 1. Guidelines on the radical management of patients with lung cancer, <i>Thorax</i> 2010;65(Suppl III):iii1eiii27 2. NICE clinical guideline 121, Lung cancer: The diagnosis and treatment of lung cancer, April 2011
Country ownership requires public sector health system strengthening
Authors: Scott Barnhart, Amy Hagopian
Journal: The Lancet Global Health (2013)

We appreciate the views of Chris Collins and Chris Beyrer,1Collins C Beyrer C Country ownership and the turning point for HIV/AIDS.Lancet Glob Health. 2013; 1: e319-e320Summary Full Text Full Text PDF Scopus (16) Google Scholar who represent a non-governmental organisation (amfAR) that has worked closely with the US President's Emergency Plan for AIDS Relief (PEPFAR) for many years. They caution that “quick transitions” to government ownership of AIDS programming “could seriously undermine sustainability”. One of the primary flaws of PEPFAR was that it failed to invest much (certainly initially) in health system strengthening, and therefore the health gains from treatment intervention were entirely unsustainable without continued donor involvement. Country ownership should mean government ownership, because only governments are accountable to populations, especially the very poor. Lessons from the transition of India's Avahan HIV prevention programme to government ownership are helpful.2Ooms G Stuckler D Basu S McKee M Financing the Millennium Development Goals for health and beyond: sustaining the ‘Big Push’.Global Health. 2010; 6: 17Crossref PubMed Scopus (30) Google Scholar This programme, funded by the Bill & Melinda Gates Foundation, was designed with transition to the government in mind, with the programme's focus, goals, and priorities aligned with those of the Indian Government from the very start. Collins and Beyrer urge funders to go slow in their transition to government ownership to ensure no disruption in HIV treatment programmes. We argue that to sustain care, countries are better served by a rapid scale-up in public-sector health system strengthening. The greatest burden of disease in all countries is from the many non-HIV illnesses and injuries, so scale-up can have broad effects on the overall burden of disease. The success realised by PEPFAR should now give way to an even more massive scale-up, of Marshall Plan proportions, to strengthen every low-income country health system.3Sgaier SK Ramakrishnan A Dhingra N et al.How the Avahan HIV prevention program transitioned from the Gates Foundation to the government of India.Health Affairs. 2013; 32: 7Crossref Scopus (46) Google Scholar Only with strong health systems can we sustain our gains on HIV/AIDS while also working towards real progress on the Millennium Development Goals and the enormous burden of other health problems. The extent to which donors and implementers involve themselves in direct government-sector investment mirrors their confidence in the strengths of health systems to care for the full spectrum of diseases and their commitment to true country leadership and ownership. We are funded on PEPFAR projects, including direct service implementation and a project in Uganda studying the effects of PEPFAR on non-HIV related health services.
Branched Chain Amino Acid Oxidation in Cultured Rat Skeletal Muscle Cells
Authors: William M. Pardridge, Delia Casanello-Ertl, Luiza Duducgian-Vartavarian
Journal: Journal of Clinical Investigation (1980)

Leucine metabolism in skeletal muscle is linked to protein turnover. Since clofibrate is known both to cause myopathy and to decrease muscle protein content, the present investigations were designed to examine the effects of acute clofibrate treatment on leucine oxidation. Rat skeletal muscle cells in tissue culture were used in these studies because cultivated skeletal muscle cells, like muscle in vivo, have been shown to actively utilize branched chain amino acids and to produce alanine. The conversion of [1-14C]leucine to 14CO2 or to the [1-14C]keto-acid of leucine (α-keto-isocaproate) was linear for at least 2 h of incubation; the production of 14CO2 from [1-14C]leucine was saturable with a Km = 6.3 mM and a maximum oxidation rate (Vmax) = 31 nmol/mg protein per 120 min. Clofibric acid selectively inhibited the oxidation of [1-14C]leucine (Ki = 0.85 mM) and [U-14C]isoleucine, but had no effect on the oxidation of [U-14C]glutamate, -alanine, -lactate, or -palmitate. The inhibition of [1-14C]leucine oxidation by clofibrate was also observed in the rat quarter-diaphragm preparation. Clofibrate primarily inhibited the production of 14CO2 and had relatively little effect on the production of [1-14C]keto-acid of leucine. A physiological concentration—3.0 g/100 ml—of albumin, which actively binds clofibric acid, inhibited but did not abolish the effects of a 2-mM concentration of clofibric acid on leucine oxidation. Clofibrate treatment stimulated the net consumption of pyruvate, and inhibited the net production of alanine. The drug also increased the cytosolic NADH/NAD+ ratio as reflected by an increase in the lactate/pyruvate ratio, in association with a decrease in cell aspartate levels. The changes in pyruvate metabolism and cell redox state induced by the drug were delayed compared with the nearly immediate inhibition of leucine oxidation. These studies suggest that clofibric acid, in concentrations that approximate high therapeutic levels of the drug, selectively inhibits branched chain amino acid oxidation, possibly at the level of the branched chain keto-acid dehydrogenase.
An iatrogenic pandemic of panic
Authors: Luc Bonneux, Wim Van Damme
Journal: BMJ (2006)

Nine decades after the disappearance of the infamous Spanish flu, its ghost is threatening again. In many countries, panicking citizens are buying drugs from uncertain sources through the internet for a disease that does not yet exist.1 In September 2005, Dr Nabarro, the World Health Organization's public health expert coordinating the response to avian influenza, told the Associated Press that a global avian influenza pandemic could kill 150 million people worldwide.2 What are the risks of a pandemic and is stockpiling antiviral drugs the best response?

A new pandemic with a highly pathogenic influenza strain is obviously possible. But other infectious agents present similar risks—for example, an Ebola epidemic with airborne transmission, an AIDS epidemic with a much more virulent strain of HIV (superbug), or massive food poisoning such as the dioxin crisis. Airborne transmission of the extremely lethal Ebola Zaire virus might cause a devastating epidemic and is popular in both fiction and (alleged) non-fiction. The HIV superbug appeared in February 2005 in New York as a virus with multiple mutations, multiple drug resistance, and a rapid course of infection, but in only one person. The case served to rekindle the US public's fear after interest in AIDS had been waning because of Iraq.

In the Belgian dioxin crisis, dioxins got mixed up in the food chain, causing levels of exposure to dioxins similar to those in the 1980s.3 The crisis fell conveniently (for the political opposition) just before an election. Competitors in the highly regulated European food market saw their chance to increase market shares. Seven million chicken and 60 000 pigs were slaughtered. Not one person has been detected with any observable consequence of dioxin poisoning.

In a global world with global media coverage and competition for sensational news, any hypothetical doomsday scenario that …
Response assessment in recurrent glioblastoma treated with irinotecan-bevacizumab: comparative analysis of the Macdonald, RECIST, RANO, and RECIST + F criteria
Authors: J. G. Perez-Larraya, M. Lahutte, G. Petrirena, G. Reyes-Botero, A. Gonzalez-Aguilar, C. Houillier, R. Guillevin, M. Sanson, K. Hoang-Xuan, J.-Y. Delattre
Journal: Neuro-Oncology (2012)

Traditionally, the most widely used criteria for response assessment in glioblastoma have been Macdonald and the Response Evaluation Criteria In Solid Tumors (RECIST). Recently, new criteria addressing contrast enhancement and fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity have been defined (the Response Assessment in Neuro-Oncology criteria) to better evaluate the effect of antiangiogenic therapy. Whether FLAIR/T2 imaging could also be helpful to refine RECIST criteria remains unresolved. This study proposed the RECIST + F criteria and compared the 4 methods (Macdonald, RECIST, RANO, and RECIST + F) to determine their agreement in identifying response and progression of recurrent glioblastomas to irinotecan-bevacizumab. Patients with recurrent glioblastoma treated with second-line irinotecan-bevacizumab were eligible. Clinical status, corticosteroid dose, and 1-dimensional and 2-dimensional measurements of tumor contrast enhancement and FLAIR hyperintensity were retrospectively assessed. Response and progression were determined according to each set of criteria. Seventy-eight patients were included. Response rates ranged from 34.2% with RECIST + F to 44.7% with Macdonald criteria. Agreement among the 4 methods in determining response and type of progression was high (kappa statistic > 0.75). One-third of patients exhibited nonenhancing progression with stable or improved contrast enhancement. Median progression-free survival was predicted by RECIST, at 13.6 weeks; RECIST + F, 12.3; Macdonald, 12.7; and RANO, 11.7 (P = .840). Intra- and interobserver correlations were high for both contrast enhancement and FLAIR hyperintensity measurements. There was a strong concordance among the different methods in determining response and progression to irinotecan-bevacizumab. Criteria integrating FLAIR hyperintensity tended, however, to reduce response rates and progression-free survival compared with criteria considering only contrast enhancement. The 1-dimensional approach appeared to be as valid as the 2-dimensional approach.
Does health related quality of life predict severe physical inactivity in COPD
Authors: Jane L. Canavan, Claire M. Nolan, Samantha S.C. Kon, Mehul S. Patel, Sarah E. Jones, Amy L. Clark, Michael I. Polkey, William D.-C. Man
Journal: European Respiratory Journal (2013)

Introduction   In patients with chronic obstructive pulmonary disease (COPD), physical inactivity (PIA) is an important predictor of mortality (Waschki et al 2011); however, measurement of physical activity levels (PAL) determined using accelerometers requires sustained use over a number of days and so their practicality outside of research is reduced. Prediction of PAL using routine clinical tools is appealing. Many health-related quality of life questionnaires (HRQoL) consider activities of daily living and hence may be used to stratify physical activity (PA).   Aims   To determine the ability of commonly used HRQoL questionnaires to identify PIA in COPD.   Methods   In 131 COPD patients (86M:45F) PA was monitored for 7 days using an accelerometer (Sensewear®) (SWA) with PAL calculated as previously described (Watz et al., 2009). Patients also completed the St. George’s Respiratory Disease Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ), the Clinical COPD Questionnaire (CCQ), the COPD Assessment Tool (CAT) and the MRC dyspnoea score. Receiver operating characteristic (ROC) plots were constructed to evaluate the ability of the questionnaires to predict a PAL    Results   Daily median SWA wear time was greater than 23 hours. Baseline characteristics: mean (SD) FEV1 51.0 (21.0)%, BMI 28.4 (5.9), median (25 th , 75 th  centiles) incremental shuttle walk 270 (170, 360). The only significant predictor was MRC dyspnoea score (≥3) (AUC 0.6, p=0.047), but sensitivity was only 75% and specificity 42%.   Conclusion   Health related quality of life questionnaires are unable to accurately predict severe physical inactivity.
Soluble factors in tolerance and contact sensitivity to 2,4-dinitrofluorobenzene in mice. III. Histocompatibility antigens associated with the hapten dinitrophenol serve as target molecules on 2,4-dinitrofluorobenzene-immune T cells for soluble suppressor factor.
Authors: J W Moorhead
Journal: The Journal of Experimental Medicine (1979)

Previous studies have shown that suppression of 2,4-dinitrofluorobenzene (DNFB) contact sensitivity by soluble suppressor factor (SSF) requires that the donor of immune lymph node (LN) cells and of SSF share either the H-2K and/or H-2D region of the major histocompatibility complex. Thus, target or acceptor molecules for SSF appear to be coded for by genes within the H-2K and H-2D loci. Experiments were done to investigate the nature of these target molecules and to determine what cell types expressed them. It was found that purified lymph node T cells are suppressed by SSF indicating that T cells express the acceptor molecules. Adsorption experiments showed that the only cells capable of adsorbing the suppressor factor are DNFB-immune T cells from donors which share with the factor-producing strain either the H-2K or H-2D locus. This adsorption can be specifically blocked by pretreating the immune LN cells with antibodies directed against H-2K and/or H-2D determinants or against the hapten DNP but not by antibodies against Ia or theta-antigens. Collectively, these results indicate that the target molecules are expressed only by DNFB-immune T cells and are comprised of histocompatibility antigens associated with DNP.
Remarkable Abundance and Evolution of Mobile Group II Introns in Wolbachia Bacterial Endosymbionts
Authors: S. Leclercq, I. Giraud, R. Cordaux
Journal: Molecular Biology and Evolution (2010)

The streamlined genomes of ancient obligate endosymbionts generally lack transposable elements, as a consequence of their intracellular confinement. Yet, the genomes of Wolbachia, one of the most abundant bacterial endosymbionts on Earth, are littered with transposable elements, in particular insertion sequences (ISs). This paradox raises the question of whether or not such a mobile DNA proliferation reflects a special feature of ISs. In this study, we focused on another class of transposable elements, group II introns, and conducted an in-depth analysis of their content and the microevolutionary processes responsible for their dynamics within Wolbachia genomes. We report an exceptionally high intron abundance and striking differences in copy numbers between Wolbachia strains as well as between intron families. Our bioinformatics and experimental results provide strong evidence that intron diversity is mainly caused by recent (and perhaps ongoing) mobility and horizontal transfers. Our data also support several temporally independent intron invasions during Wolbachia evolution. Furthermore, group II intron spread in some Wolbachia strains may be regulated through gene conversion–mediated inactivation of intron copies. Finally, we found introns to be involved in numerous genomic rearrangements. This underscores the high recombinogenic potential of group II introns, contrary to general expectations. Overall, our study represents the first comprehensive analysis of group II intron evolutionary dynamics in obligate intracellular bacteria. Our results show that bacterial endosymbionts with reduced genomes can sustain high loads of mobile group II introns, as hypothesized for the endosymbiont ancestor of mitochondria during early eukaryote evolution.
Modification of nasal membrane potential difference with inhaled amiloride and loperamide in the cystic fibrosis (CF) mouse.
Authors: S. Ghosal, C. J. Taylor, J. McGaw
Journal: Thorax (1996)

BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination of defective cAMP mediated chloride secretion and enhanced sodium absorption leads to dehydration of mucosal mucus and is reflected in an increased trans-epithelial potential difference (PD). The airway secretions may be less viscid and easier to expectorate if sodium (and water) reabsorption is inhibited. METHODS: To evaluate the response to sodium blocking agents, changes in the nasal PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain) before and after administration of nebulised amiloride and loperamide (both in a concentration of 1 mmol/l). The duration of action for both drugs was also determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The median basal PD was -24 mV in controls and -28 mV in CF mice (p &lt; 0.01). This fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV, respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p &lt; 0.01). There was no further change in PD when loperamide was given after amiloride. This suggests that loperamide and amiloride may act on sodium absorption via similar mechanisms. Loperamide had a longer duration of action after a single administration than amiloride. CONCLUSION: The administration of amiloride and loperamide reduces the transepithelial potential and inhibits sodium reabsorption in the CF mouse airway. Further studies are required to determine if the more prolonged action of loperamide could be of therapeutic use.
Lactate clearance is not inferior to central venous oxygen saturation as a goal in early sepsis resuscitation
Authors: A. Dunscombe
Journal: Thorax (2010)

Goal-directed therapy in severe sepsis improves outcome by providing protocol-driven targets for initial resuscitation. Current guidelines use central venous oxygen saturations (Scvo2) to assess oxygen delivery and metabolism, but this requires specialist equipment and expertise which may limit its use. This study addresses whether a change in serum lactate concentration …