Leadership in strategic information (LSI) building skilled public health capacity in Ethiopia

<p>Abstract</p> <p>Background</p> <p>In many developing countries, including Ethiopia, few have the skills to use data for effective decision making in public health. To address this need, the U.S. Centers for Disease Control and Prevention (CDC), in collaboration with two local Ethiopian organizations, developed a year long Leadership in Strategic Information (LSI) course to train government employees working in HIV to use data from strategic information sources. A process evaluation of the LSI course examined the impact of the training on trainees' skills and the strengths and weaknesses of the course. The evaluation consisted of surveys and focus groups.</p> <p>Findings</p> <p>Trainees' skill sets increased in descriptive and analytic epidemiology, surveillance, and monitoring and evaluation (M and E). Data from the evaluation indicated that the course structure and the M and E module required revision in order to improve outcomes. Additionally, the first cohort had a high attrition rate. Overall, trainees and key stakeholders viewed LSI as important in building skilled capacity in public health in Ethiopia.</p> <p>Conclusion</p> <p>The evaluation provided constructive insight in modifying the course to improve retention and better address trainees' learning needs. Subsequent course attrition rates decreased as a result of changes made based on evaluation findings.</p

Referral of patients with depression to mental health care by Dutch general practitioners: an observational study

<p>Abstract</p> <p>Background</p> <p>Depression is a common illness, often treated in primary care. Guidelines provide recommendations for referral to mental health care. Several studies investigated determinants of referral, none investigated guideline criteria as possible determinants.</p> <p>We wanted to evaluate general practitioner's referral of depressed patients to mental health care and to what extent this is in agreement with (Dutch) guideline recommendations.</p> <p>Methods</p> <p>We used data of primary care respondents from the Netherlands Study of Depression and Anxiety with major depressive disorder in the past year (n = 478). We excluded respondents with missing data (n = 134). Referral data was collected from electronic patient files between 1 year before and after baseline and self report at baseline and 1-year follow-up. Logistic regression was used to describe association between guideline referral criteria (e.g. perceived need for psychotherapy, suicide risk, severe/chronic depression, antidepressant therapy failure) and referral.</p> <p>Results</p> <p>A high 58% of depressed patients were referred. Younger patients, those with suicidal tendency, chronic depression or perceived need for psychotherapy were referred more often. Patients who had used ≥2 antidepressants or with chronic depression were more often referred to secondary care. Referred respondents met on average more guideline criteria for referral. However, only 8-11% of variance was explained.</p> <p>Conclusion</p> <p>The majority of depressed patients were referred to mental health care. General practitioners take guideline criteria into account in decision making for referral of depressed patients to mental health care. However, other factors play a part, considering the small percentage of variance explained. Further research is necessary to investigate this.</p

Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors <em>in vitro</em>

Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD(+) as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure of the weak inhibitor 5-aminoiso quinolin-1-one, 3-aryl-5-substituted-isoquinolin-1-ones were designed as inhibitors to explore the structure-activity relationships (SARs) for binding and to define the shape of a hydrophobic cavity in the active site. 5-Amino-3-arylisoquinolinones were synthesised by Suzuki-Miyaura coupling of arylboronic acids to 3-bromo-1-methoxy-5-nitro-isoquinoline, reduction and O-demethylation. 3-Aryl-5-methylisoquinolin-1-ones, 3-aryl-5-fluoroisoquinolin-1-ones and 3-aryl-5-methoxyisoquinolin-1-ones were accessed by deprotonation of 3-substituted-N,N,2-trimethylbenzamides and quench with an appropriate benzonitrile. SAR around the isoquinolinone core showed that aryl was required at the 3-position, optimally with a para-substituent. Small meta-substituents were tolerated but groups in the ortho-positions reduced or abolished activity. This was not due to lack of coplanarity of the rings, as shown by the potency of 4,5-dimethyl-3-phenylisoquinolin-1-one. Methyl and methoxy were optimal at the 5-position. SAR was rationalised by modelling and by crystal structures of examples with TNKS-2. The 3-aryl unit was located in a large hydrophobic cavity and the para-substituents projected into a tunnel leading to the exterior. Potency against TNKS-1 paralleled potency against TNKS-2. Most inhibitors were highly selective for TNKSs over PARP-1 and PARP-2. A range of highly potent and selective inhibitors is now available for cellular studies.</p

Peasant settlers and the ‘civilizing mission’ in Russian Turkestan, 1865-1917

This article provides an introduction to one of the lesser-known examples of European settler colonialism, the settlement of European (mainly Russian and Ukrainian) peasants in Southern Central Asia (Turkestan) in the late nineteenth and early twentieth centuries. It establishes the legal background and demographic impact of peasant settlement, and the role played by the state in organising and encouraging it. It explores official attitudes towards the settlers (which were often very negative), and their relations with the local Kazakh and Kyrgyz population. The article adopts a comparative framework, looking at Turkestan alongside Algeria and Southern Africa, and seeking to establish whether paradigms developed in the study of other settler societies (such as the ‘poor white’) are of any relevance in understanding Slavic peasant settlement in Turkestan. It concludes that there are many close parallels with European settlement in other regions with large indigenous populations, but that racial ideology played a much less important role in the Russian case compared to religious divisions and fears of cultural backsliding. This did not prevent relations between settlers and the ‘native’ population deteriorating markedly in the years before the First World War, resulting in large-scale rebellion in 1916

5-benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2)

PARP-2 is a member of the poly(ADP-ribose) polymerase family, with some activities similar to those of PARP-1 but with other distinct roles. Two series of isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors of PARP-2, using the structures of the catalytic sites of the isoforms. A new efficient synthesis of 5-aminoisoquinolin-1-one was developed, and acylation with acyl chlorides gave 5-acylaminoisoquinolin-1-ones. By examination of isoquinolin-1-ones with carboxylates tethered to the 5-position, Heck coupling of 5-iodoisoquinolin-1-one furnished the 5-CH═CHCO2H compound for reduction to the 5-propanoic acid. Alkylation of 5-aminoisoquinolin-1-one under mildly basic conditions, followed by hydrolysis, gave 5-(carboxymethylamino)isoquinolin-1-one, whereas it was alkylated at 2-N with methyl propenoate and strong base. Compounds were assayed in vitro for inhibition of PARP-1 and PARP-2, using FlashPlate and solution-phase assays, respectively. The 5-benzamidoisoquinolin-1-ones were more selective for inhibition of PARP-2, whereas the 5-(ω-carboxyalkyl)isoquinolin-1-ones were less so. 5-Benzamidoisoquinolin-1-one is the most PARP-2-selective compound (IC50(PARP-1)/IC50(PARP-2) = 9.3) to date, in a comparative study

High aboveground carbon stock of African tropical montane forests

Tropical forests store 40-50 per cent of terrestrial vegetation carbon(1). However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests(2). Owing to climatic and soil changes with increasing elevation(3), AGC stocks are lower in tropical montane forests compared with lowland forests(2). Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4 megagrams of carbon per hectare (95% confidence interval 137.1-164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network(4) and about 70 per cent and 32 per cent higher than averages from plot networks in montane(2,5,6) and lowland(7) forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa(8). We find that the low stem density and high abundance of large trees of African lowland forests(4) is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to help to guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse(9,10) and carbon-rich ecosystems. The aboveground carbon stock of a montane African forest network is comparable to that of a lowland African forest network and two-thirds higher than default values for these montane forests.Peer reviewe