Does "Low Cost" Urban Sanitation Exist? Lessons from a Global Data Set.

In this paper, we report results from, and demonstrate the value of, a global database for the collection and aggregation of reliable and comparable cost data for urban sanitation systems as they are built and operated on the ground (rather than the "as planned" costs that are often reported). We show that no particular "mode" of urban sanitation (for example "sewered sanitation" or "fecal sludge management") can be meaningfully described as "low cost" when compared to other modes. We show that economies of scale may operate for systems that transport waste from pits and sealed tanks by road as well as for sewerage. We use a case study example to show the value of being able to compare local costs to global benchmarks and identify that operational considerations such as low connection rates may be more significant in determining overall cost liabilities for urban sanitation than technical considerations such as population density, size, and degree of centralization/decentralization.

Assessment of MTR Rs1805087 SNP as Possible Modifier of Sickle Cell Disease Severity in a Nigerian Population.

BACKGROUND: Sickle cell disease is the commonest genetic disorder in Nigeria, affecting 2-3% of an estimated population of 160 million people. The role of genetic mutations in folate cycle genes, and the variable phenotypic expressions constituting disease severity, needs to be critically examined. OBJECTIVE: This study was carried out to establish the pattern of methionine synthase gene mutations (rs1805087 SNP), and its possible association with disease severity in adults with sickle cell anaemia in Lagos, Nigeria. METHODOLOGY: This is a cross-sectional study of seventy (70) subjects with sickle cell disease (HbSS) matched for age and gender with known apparently healthy haemoglobin genotype AA (HbAA) subjects, as cases and controls respectively. Structured questionnaires were used to obtain demographic, clinical and other phenotypic data needed to compute disease severity. Pattern of MTR A2756G gene mutation and homocysteine assay (Hcy) were assessed by Polymerase Chain Reaction and Enzyme- linked Immunosorbent Assay respectively. Full blood count analysis of participants was done using the KX-21 Automated Analyzer (Sysmex Corporation, Japan). RESULTS: The mutant genotypes MTR 2756 AG/GG were recorded in 46.4% (n =55) of subjects with disease severity score >7. Elevated plasma homocysteine (HHcy) was significantly associated with disease severity among HbSS subjects (OR=17.2, CI: 3.490-86.079; p=0.0001). Conversely, no significant association was observed with the mutant genotypes MTR 2756 AG/GG and disease severity (p>0.05). CONCLUSION: While HHcy is significantly associated with phenotypic expression of HbSS, the MTR 2756 SNPs did not appear to independently influence homocysteine level or disease severity in HbSS subjects.

CONTEXTE: La drépanocytose est la maladie génétique la plus répandue au Nigeria, affectant 2 à 3 % d'une population estimée à 160 millions de personnes. Le rôle des mutations génétiques dans les gènes du cycle du folate, et les expressions phénotypiques variables constituant la gravité de la maladie, doivent être examinés de façon critique. OBJECTIF: Cette étude a été menée pour établir le schéma des mutations du gène de la méthionine synthase (rs1805087 SNP), et son association possible avec la gravité de la maladie chez les adultes atteints de drépanocytose à Lagos, au Nigeria. MÉTHODOLOGIE: Il s'agit d'une étude transversale de soixantedix (70) sujets atteints de drépanocytose (HbSS) appariés pour l'âge et le sexe avec des sujets connus apparemment sains de génotype d'hémoglobine AA (HbAA), comme cas et contrôles respectivement. Des questionnaires structurés ont été utilisés pour obtenir des données démographiques, cliniques et autres données phénotypiques nécessaires au calcul de la gravité de la maladie. Le profil de la mutation du gène MTR A2756G et le dosage de l'homocystéine (Hcy) ont été évalués respectivement par réaction en chaîne par polymérase et par test immunologique enzymatique. L'analyse de la formule sanguine complète des participants a été effectuée à l'aide de l'analyseur automatisé KX-21 (Sysmex Corporation, Japon). RÉSULTATS: Les génotypes mutants MTR 2756 AG/GG ont été enregistrés chez 46,4 % (n =55) des sujets présentant un score de gravité de la maladie > 7. L'homocystéine plasmatique élevée (HHcy) était significativement associée à la gravité de la maladie chez les sujets HbSS (OR=17,2, CI : 3,490­86,079 ; p=0,0001). À l'inverse, aucune association significative n'a été observée entre les génotypes mutants MTR 2756 AG/GG et la gravité de la maladie (p>0,05). CONCLUSION: Alors que l'HHcy est significativement associée à l'expression phénotypique de l'HbSS, les SNP MTR 2756 ne semblent pas influencer indépendamment le niveau d'homocystéine ou la gravité de la maladie chez les sujets HbSS.

Machine learning-based radiomic evaluation of treatment response prediction in glioblastoma.

AIM: To investigate machine learning based models combining clinical, radiomic, and molecular information to distinguish between early true progression (tPD) and pseudoprogression (psPD) in patients with glioblastoma. MATERIALS AND METHODS: A retrospective analysis was undertaken of 76 patients (46 tPD, 30 psPD) with early enhancing disease following chemoradiotherapy for glioblastoma. Outcome was determined on follow-up until 6 months post-chemoradiotherapy. Models comprised clinical characteristics, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and 307 quantitative imaging features extracted from enhancing disease and perilesional oedema masks on early post-chemoradiotherapy contrast-enhanced T1-weighted imaging, T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Feature selection was performed within bootstrapped cross-validated recursive feature elimination with a random forest algorithm. Naive Bayes five-fold cross-validation was used to validate the final model. RESULTS: Top selected features included age, MGMT promoter methylation status, two shape-based features from the enhancing disease mask, three radiomic features from the enhancing disease mask on ADC, and one radiomic feature from the perilesional oedema mask on T2WI. The final model had an area under the receiver operating characteristics curve (AUC) of 0.80, sensitivity 78.2%, specificity 66.7%, and accuracy of 73.7%. CONCLUSION: Incorporating a machine learning-based approach using quantitative radiomic features from standard-of-care magnetic resonance imaging (MRI), in combination with clinical characteristics and MGMT promoter methylation status has a complementary effect and improves model performance for early prediction of glioblastoma treatment response.

Experiences of advance care planning in Parkinson's disease and atypical parkinsonian disorders: a mixed methods systematic review.

BACKGROUND AND PURPOSE: Advance care planning allows people to plan for their future care needs and can include medical, psychological and social aspects. However, little is known on the use, experience of and attitudes towards advance care planning in patients with parkinsonian disorders, their family carers and healthcare professionals. METHODS: A systematic search of online databases was conducted in April 2019 using a narrative synthesis approach with thematic analysis and tabulation to synthesize the findings. RESULTS: In all, 507 articles were identified and 27 were included. There were five overarching themes: (i) what is involved in advance care planning discussions, (ii) when and how advance care planning discussions are initiated, (iii) barriers to advance care planning, (iv) the role of healthcare professionals and (v) the role of the family carer. This evidence was used to highlight eight effective components to support optimal advance care planning in parkinsonian disorders: advance care planning discussions should be individualized in content, timing and approach; patients should be invited to discuss advance care planning early and regularly; palliative care services should be introduced early; a skilled professional should deliver advance care planning; support to family carers should be offered in the advance care planning process; healthcare professionals should be educated on parkinsonian disorders and palliative care; advance care planning should be clearly documented and shared with relevant services; and healthcare professionals should be enabled to conduct effective advance care planning. CONCLUSIONS: These components can inform best practice in advance care planning in patients with parkinsonian disorders.

CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study.

CINAMMON is a phase IV, open-label, single-arm, pilot study assessing maraviroc (MVC) in the central nervous system (CNS) when added to darunavir/ritonavir monotherapy (DRV/r) in virologically suppressed HIV-infected subjects. CCR5 tropic participants on DRV/r were recruited. Participants remained on DRV/r for 12 week (w) (control phase). MVC 150 mg qd was added w12-w36 (intervention phase). Lumbar puncture (LP) and neurocognitive function (Cogstate) examinations scheduled at baseline, w12 and w36; MRI before w12, again at w36. Primary endpoint was CSF inflammatory marker changes during intervention phase. Secondary endpoints included changes in NC function and MRI parameters. CSF/plasma DRV/r concentrations measured at w12 and w36, MVC at w36. Nineteen patients recruited, 15 completed (17M, 2F). Dropouts: headache (2), knee problem (could not attend, 1), personal reasons (1). Mean age (range) 45.4 years (27.2-65.1), 13/19 white, 10/19 MSM. No changes in selected CSF markers were seen w12-w36. Overall NC function did not improve w12-w36: total age adjusted z score improved by 0.27 (weighted paired t test; p = 0.11); for executive function only, age adjusted z score improved by 0.54 (p = 0.03). MRI brain parameters unchanged. DRV plasma:CSF concentration ratio unchanged between w12 (132) and w36 (112; p = 0.577, Wilcoxon signed-rank). MVC plasma:CSF concentration ratio was 35 at w36. No changes in neuroinflammatory markers seen. In this small study, addition of 24w MVC 150 mg qd to stable DRV/r monotherapy showed possible improvement in executive function with no global NC effect. Learning effect cannot be excluded. This effect should be further evaluated.

Correction to: CSF inflammatory markers and neurocognitive function after addition of maraviroc to monotherapy darunavir/ritonavir in stable HIV patients: the CINAMMON study.

Due to a production error the bottom portion of Figure 1 was omitted. The corrected figure is given below.

An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Factors influencing the quality of Myrmecia pilosula (Jack Jumper) ant venom for use in in vitro and in vivo diagnoses of allergen sensitization and in allergen immunotherapy.

BACKGROUND: Allergen immunotherapy uses pharmaceutical preparations derived from naturally occurring source materials, which contain water-soluble allergenic components responsible for allergic reactions. The success of in vivo and in vitro diagnoses in allergen sensitization and allergen immunotherapy largely depends on the quality, composition and uniformity of allergenic materials used to produce the active ingredients, and the formulation employed to prepare finished products. OBJECTIVES: We aimed to examine the factors influencing batch-to-batch consistency of Jack Jumper (Myrmecia pilosula) ant venom (JJAV) in the form of active pharmaceutical ingredient (AI) and informed whether factors such as temperature, artificial light and container materials influence the quality of JJAV AIs. We also aimed to establish handling and storage requirements of JJAV AIs to ensure preservation of allergenic activities during usage in the diagnosis of allergen sensitization and in allergen immunotherapy. METHODS: The quality and consistency of JJAV AIs were analysed using a combination of bicinchoninic acid assay for total protein quantification, HPLC-UV for JJAV allergen peptides quantification, ELISA inhibition for total allergenic potency, SDS-PAGE, AU-PAGE and immunoblot for qualitative assessment of JJAV components, and Limulus Amebocyte Lysate assay for the quantification of endotoxin concentration. API-ZYM and Zymogram assays were used to probe the presence of enzymatic activities in JJAV. RESULTS: Pharmaceutical-grade JJAV for allergen immunotherapy has good batch-to-batch consistency. Temporary storage at 4°C and light exposure do not affect the quality of JJAV. Exposure to temperature above 40°C degrades high MW allergens in JJAV. Vials containing JJAV must be stored frozen and in upright position during long-term storage. CONCLUSIONS AND CLINICAL RELEVANCE: We have identified factors, which can influence the quality and consistency of JJAV AIs, and provided a framework for appropriate handling, transporting and storage of JJAV to be used for the diagnosis of allergen sensitization and in AIT.

Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months.

PURPOSE: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). METHODS: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. RESULTS: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p < 0.001), radiotherapy (p < 0.05), and reported poorer QoL (p = 0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p < 0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year CONCLUSIONS: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs.

Non-inferiority of minimally invasive oesophagectomy: an 8-year retrospective case series.

BACKGROUND: The trend towards laparoscopic surgery seen in other specialties has not occurred at the same pace in oesophagectomy. This stems from concerns regarding compromised oncological clearance, and complications associated with gastric tube necrosis and anastomotic failure. We present our experience of minimally invasive oesophagectomy (MIO) compared to open and hybrid surgery. We aim to ascertain non-inferiority of MIO by evaluating impact on survival, oncological clearance by resection margin and lymph node harvest and post-operative complications. METHODS: Data were sourced retrospectively 2008-2015. Three approaches were studied. MIO (3-stage Mckeown), hybrid (2-stage Ivor Lewis, laparoscopy, thoracotomy) and open (2-stage Ivor Lewis). RESULTS: Five-year survival was 54.2%. Surgical approach had no significant impact on survival at any stage of disease (Stage 0/I p = 0.98; stage II p = 0.2; stage III p = 0.76). There was no statistically significant difference in oncological clearance by resection margins between procedures when compared by disease stage (p = 0.49). A higher number of nodes were harvested in hybrid [median 27.5 (6-65)] and open surgeries [median 26 (4-54)] than in MIO [median 20 (7-44)] (p > 0.01). Numbers of nodes resected did not impact risk of recurrence [recurrence, median 25 (6-54), no recurrence, 26 (4-65)] (p = 0.25). Anastomotic strictures (22.4%) and potential leaks (17.9%) were more common in MIO (strictures p > 0.01, leaks p = 0.08), although associated morbidity was lower. Respiratory complications were less common in MIO (2.9%) versus hybrid (13.3%) (p = 0.02). Wound infection and chyle leak were also lower (wound 1.5% MIO 3.5% open, p = 0.6; chyle leak 1.5% MIO, 6.7% hybrid, p = 0.2). CONCLUSIONS: Our results show no negative impact of MIO on survival or oncological clearance. Respiratory and wound complications are lower in MIO, but rates of anastomotic strictures and potential anastomotic leaks are increased. This may be due to the longer length of conduit and subclinical ischaemia at the anastomosis and merits further evaluation.

Neuroimaging in encephalitis: analysis of imaging findings and interobserver agreement.

AIM: To assess the role of imaging in the early management of encephalitis and the agreement on findings in a well-defined cohort of suspected encephalitis cases enrolled in the Prospective Aetiological Study of Encephalitis conducted by the Health Protection Agency (now incorporated into Public Health England). MATERIALS AND METHODS: Eighty-five CT examinations from 68 patients and 101 MRI examinations from 80 patients with suspected encephalitis were independently rated by three neuroradiologists blinded to patient and clinical details. The level of agreement on the interpretation of images was measured using the kappa statistic. The sensitivity, specificity, and negative and positive predictive values of CT and MRI for herpes simplex virus (HSV) encephalitis and acute disseminated encephalomyelitis (ADEM) were estimated. RESULTS: The kappa value for interobserver agreement on rating the scans as normal or abnormal was good (0.65) for CT and moderate (0.59) for MRI. Agreement for HSV encephalitis was very good for CT (0.87) and MRI (0.82), but only fair for ADEM (0.32 CT; 0.31 MRI). Similarly, the overall sensitivity of imaging for HSV encephalitis was ∼80% for both CT and MRI, whereas for ADEM it was 0% for CT and 20% for MRI. MRI specificity for HSV encephalitis between 3-10 days after symptom onset was 100%. CONCLUSION: There is a subjective component to scan interpretation that can have important implications for the clinical management of encephalitis cases. Neuroradiologists were good at diagnosing HSV encephalitis; however, agreement was worse for ADEM and other alternative aetiologies. Findings highlight the importance of a comprehensive and multidisciplinary approach to diagnosing the cause of encephalitis that takes into account individual clinical, microbiological, and radiological features of each patient.

Moderate-intensity exercise alters markers of alternative activation in circulating monocytes in females: a putative role for PPARγ.

PURPOSE: Monocytes may be primed towards differentiation into classically activated M1 macrophages or alternatively activated M2 macrophages. M1 macrophages greatly contribute to the inflammation which promotes insulin resistance, whereas M2 macrophages resolve inflammation. We have previously shown that exercise increases M2 marker expression in mixed mononuclear cells, possibly via activation of the nuclear transcription factor PPARγ. However, these effects have not been demonstrated specifically within monocytes. Thus, we aimed to investigate whether moderate-intensity exercise elicited similar effects on monocytic M1/M2 marker expression and PPARγ activity to those reported previously in mononuclear cells, so as to further elucidate the mechanisms by which exercise may alter inflammatory status and, accordingly, prevent insulin resistance. METHODS/RESULTS: 19 sedentary females completed an 8 week moderate-intensity exercise programme (walking 45 min, thrice weekly). Monocytes were isolated from blood via immunomagnetic separation; monocyte expression of M2 markers (Dectin-1: 2.6 ± 1.9-fold; IL-10: 3.0 ± 2.8-fold) significantly increased, whilst the expression of the M1 marker MCP-1 significantly decreased (0.83 ± 0.2 cf. basal), over the duration of the programme. Serum PPARγ activity levels and PPARγ target-genes (CD36: 1.9 ± 1.5-fold; LXRα: 5.0 ± 4.7-fold) were significantly increased after the 8 week exercise programme. Associated with these effects were significant improvements in systemic insulin sensitivity (McAuley's ISI: Δ0.98 M/mU/L cf. basal). CONCLUSION: Exercise participation suppressed M1 markers and induced M2 markers in monocytes, potentially via PPARγ-triggered signalling, and these effects may contribute (perhaps via priming of monocytes for differentiation into M2 tissue-macrophages) to improved systemic insulin sensitivity in exercising participants. These findings provide an alternative mechanism by which exercise may exert its anti-inflammatory effects in order to prevent insulin resistance and type 2 diabetes.

Synovial fluid bupivacaine concentrations following single intra-articular injection in normal and osteoarthritic canine stifles.

Intra-articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra-articular injection. Eight healthy beagles with normal stifles and 22 large and giant-breed dogs with stifle osteoarthritis (OA) were treated with a single intra-articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra-articular injection.

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate.

BACKGROUND: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. METHODS: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). RESULTS: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. CONCLUSIONS: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required.

Ornithine phenylacetate targets alterations in the expression and activity of glutamine synthase and glutaminase to reduce ammonia levels in bile duct ligated rats.

BACKGROUND & AIMS: In liver failure, ammonia homeostasis is dependent upon the function of the ammonia metabolising enzymes, glutamine synthetase (GS) and glutaminase (GA) but data about their protein expression and activity are lacking. The aims of this study were to determine the protein expression and activity of GS and GA in individual organs in a rat model of chronic liver disease and to test whether the treatment with the ammonia-lowering agent ornithine phenylacetate (OP) modulates their activities. METHODS: 49 SD rats were studied 35 days after sham-operation or bile duct ligation (BDL). The BDL group received: L-ornithine (0.6 mg/kg/day), Phenylacetate (0.6 mg/kg/day), OP (0.6 mg/kg/day) or placebo (saline) for 5 days prior to sacrifice. Arterial ammonia, amino acids and liver biochemistry were measured. Expressions of GS and GA were determined by Western-blotting and activities by end-point methods in liver, muscle, gut, kidney, lung, and frontal cortex. RESULTS: In BDL rats, hepatic GS enzyme activity was reduced by more than 80% compared to sham rats. Further, in BDL rats GA activity was reduced in liver but increased in the gut, muscle and frontal cortex compared to sham rats. OP treatment resulted in a reduction in hyperammonemia in BDL rats, associated with increased GS activity in the muscle and reduced gut GA activity. CONCLUSIONS: In a rat model of chronic liver failure, hyperammonemia is associated with inadequate compensation by liver and muscle GS activity and increased gut GA activity. OP reduces plasma ammonia by increasing GS in the muscle and reducing GA activity in the gut providing additional insights into its mechanism of its action. GS and GA may serve as important future therapeutic targets for hyperammonemia in liver failure.

Evolution of paternal care in diploid and haplodiploid populations.

W. D. Hamilton famously suggested that the inflated relatedness of full sisters under haplodiploidy explains why all workers in the social hymenoptera are female. This suggestion has not stood up to further theoretical scrutiny and is not empirically supported. Rather, it appears that altruistic sib-rearing in the social hymenoptera is performed exclusively by females because this behaviour has its origins in parental care, which was performed exclusively by females in the ancestors of this insect group. However, haplodiploidy might still explain the sex of workers if this mode of inheritance has itself been responsible for the rarity of paternal care in this group. Here, we perform a theoretical kin selection analysis to investigate the evolution of paternal care in diploid and haplodiploid populations. We find that haplodiploidy may either inhibit or promote paternal care depending on model assumptions, but that under the most plausible scenarios it promotes - rather than inhibits - paternal care. Our analysis casts further doubt upon there being a causal link between haplodiploidy and eusociality.

Neurofilament heavy chain as a marker of neuroaxonal pathology and prognosis in acute encephalitis.

BACKGROUND AND PURPOSE: The neurological outcome of acute encephalitis can be devastating and early prognosis remains difficult. Biomarkers that quantify the extent of early brain injury are needed to improve the prognostic accuracy and aid patient management. Our objective was to assess whether cerebrospinal fluid (CSF) protein biomarkers of neuroaxonal and glial cell injury are elevated in distinct forms of acute encephalitis and predictive of poor outcome. METHODS: This was a prospective study of patients presenting with acute encephalitis to three teaching hospitals in London, UK. Levels of neurofilament heavy chain (NfH, SMI35) and S100B were quantified in CSF using enzyme-linked immunosorbent assay. The outcome was assessed by the Glasgow Outcome Scale (GOS). RESULTS: Fifty-six patients with acute encephalitis were recruited and classified into the following diagnostic categories: infectious (n = 20), inflammatory (n = 14) and unknown etiology (n = 22). Pathological levels of NfH and S100B were observed in 24/56 (43%) and 54/56 (96%), respectively. Patients with infectious encephalitis had significantly higher NfH levels compared with the other two groups (P < 0.05). A poor outcome (GOS < 5) was associated with significantly higher CSF NfH levels within samples taken 2 weeks after symptom onset. CONCLUSIONS: This study suggests that longitudinal CSF NfH levels are of superior prognostic value compared with CSF S100B levels. Prolonged release of NfH, a marker of neuroaxonal damage, was associated with poor outcome. Potentially there is a window of opportunity for future neuroprotective treatment strategies in encephalitis.

Screening for HIV-related neurocognitive impairment in clinical practice: challenges and opportunities.

With increasingly successful management of HIV, focus has shifted away from AIDS-related complications to other chronic co-morbidities. For HIV-related cognitive problems, the true aetiopathogenesis and epidemiology remains unclear. Rather than a systematic review, this paper presents the challenges and the opportunities we faced in establishing our own clinical service. Papers were identified using Pubmed and the terms "screening", "HIV" and "neurocognitive". This article covers the background of HIV-associated neurocognitive disorders (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing classification, prevalence, diagnostic categories and diagnostic uncertainties. Screening is discussed, including a comparison of the available screening tools for cognitive deficits in HIV-infected patients and the importance of practice effects. Discussed also are the normal ranges and the lack thereof and potential investigations for those found to have impairments. We conclude by discussing the role of NCI screening in routine clinical care at the current time.