A comparison of chest radiographic findings in human immunodeficiency virus-positive and -negative children with pulmonary tuberculosis.

AIM: To compare chest radiography (CXR) findings in human immunodeficiency virus (HIV)-positive and HIV-negative children who had microbiologically confirmed pulmonary tuberculosis (PTB). MATERIALS AND METHODS: Retrospective analysis of CXRs from children with known HIV status and microbiologically confirmed PTB (culture or GeneXpert Xpert MTB/RIF positive), who were hospitalised or seen at a primary healthcare centre over a 5-year period. Radiological findings were compared according to HIV and nutritional status. RESULTS: CXRs of 130 children were analysed from 35 (27%) HIV- positive and 95 (73%) HIV-negative children with confirmed PTB, median age 45.7 months (interquartile range [IQR] 18-81.3 months). CXR changes consistent with PTB were reported in 21/35 (60%) of HIV-positive and 59/95 (62%) of HIV-negative patients, (p=0.81). Normal CXR was identified in 3/35 (8.6%) of HIV-positive and 5/95 (5.3%) of HIV-negative patients (p=0.81). Airway compression was present in 3/35 (8.6%) of HIV-positive and 7/95 (7.4%) of HIV-negative patients (p>0.99). Overall, lymphadenopathy was identified in 42/130 (32.3%) of patients, 11/35 (31.4 %) were HIV-positive compared with 31/95 (32.6%) HIV-negative patients. Airspace consolidation was present in 60% of both HIV-positive (21/35) and HIV-negative patients (57/95). Pleural effusion was present in 2/35 (5.7 %) of HIV-negative and 9/95 (9.5 %) of HIV-negative patients. There were no statistically significant radiological differences by HIV group. CONCLUSION: There were no significant differences in the CXR findings between the HIV-positive and HIV-negative children with confirmed PTB.

Markers of human endometrial hypoxia can be detected in vivo and ex vivo during physiological menstruation.

STUDY QUESTION: Can markers of human endometrial hypoxia be detected at menstruation in vivo? SUMMARY ANSWER: Our in vivo data support the presence of hypoxia in menstrual endometrium of women during physiological menstruation. WHAT IS KNOWN ALREADY: Current evidence from animal models and human in vitro studies suggests endometrial hypoxia is present at menstruation and drives endometrial repair post menses. However, detection of human endometrial hypoxia in vivo remains elusive. STUDY DESIGN, SIZE, DURATION: We performed a prospective case study of 16 women with normal menstrual bleeding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reproductively aged female participants with a regular menstrual cycle underwent objective measurement of their menstrual blood loss using the alkaline haematin method to confirm a loss of <80 ml per cycle. Exclusion criteria were exogenous hormone use, an intrauterine device, endometriosis or fibroids >3 cm. Participants attended for two MRI scans; during days 1-3 of menstruation and the early/mid-secretory phase of their cycle. The MRI protocol included dynamic contrast-enhanced MRI and T2* quantification. At each visit, an endometrial sample was also collected and hypoxia-regulated repair factor mRNA levels (ADM, VEGFA, CXCR4) were quantified by RT-qPCR. MAIN RESULTS AND THE ROLE OF CHANCE: Women had reduced T2* during menstrual scans versus non-menstrual scans (P = 0.005), consistent with menstrual hypoxia. Plasma flow (Fp) was increased at menstruation compared to the non-menstrual phase (P = 0.0005). Laboratory findings revealed increased ADM, VEGF-A and CXCR4 at menstruation on examination of paired endometrial biopsies from the menstrual and non-menstrual phase (P = 0.008; P = 0.03; P = 0.009). There was a significant correlation between T2* and these ex vivo hypoxic markers (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This study examined the in vivo detection of endometrial hypoxic markers at specific timepoints in the menstrual cycle in women with a menstrual blood loss <80 ml/cycle and without significant uterine structural abnormalities. Further research is required to determine the presence of endometrial hypoxia in those experiencing abnormal uterine bleeding with and without fibroids/adenomyosis. WIDER IMPLICATIONS OF THE FINDINGS: Heavy menstrual bleeding (HMB) is a common, debilitating condition. Understanding menstrual physiology may improve therapeutics. To our knowledge, this is the first in vivo data supporting the presence of menstrual hypoxia in the endometrium of women with normal menstrual bleeding. If aberrant in those with HMB, these non-invasive tests may aid diagnosis and facilitate personalized treatments for HMB. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Wellbeing of Women grant RG1820, Wellcome Trust Fellowship 209589/Z/17/Z and undertaken in the MRC Centre for Reproductive Health, funded by grants G1002033 and MR/N022556/1. H.O.D.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc; Myovant Sciences GmbH. H.O.D.C. receives royalties from UpToDate for articles on abnormal uterine bleeding. TRIAL REGISTRATION NUMBER: N/A.

Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The aim of this study was to investigate patients with amyotrophic lateral sclerosis in order to determine their nutritional, neurological and respiratory parameters, and survival according to metabolic level. METHODS: Nutritional assessment included resting energy expenditure (REE) measured by indirect calorimetry [hypermetabolism if REE variation (ΔREE) > 10%] and fat mass (FM) using impedancemetry. Neurological assessment included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score. Survival analysis used the Kaplan-Meier method and multivariate Cox model. RESULTS: A total of 315 patients were analysed. Median age at diagnosis was 65.9 years and 55.2% of patients were hypermetabolic. With regard to the metabolic level (ΔREE: < 10%, 10-20% and >20%), patients with ΔREE > 20% initially had a lower FM(29.7% vs. 32.1% in those with ΔREE ≤10%; P = 0.0054). During follow-up, the median slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised tended to worsen more in patients with ΔREE > 20% (-1.4 vs. -1.0 points/month in those with ΔREE ≤10%; P = 0.07). Overall median survival since diagnosis was 18.4 months. ΔREE > 20% tended to increase the risk of dying compared with ΔREE ≤10% (hazard ratio, 1.33; P = 0.055). In multivariate analysis, an increased REE:FM ratio was independently associated with death (hazard ratio, 1.005; P = 0.001). CONCLUSIONS: Hypermetabolism is present in more than half of patients with amyotrophic lateral sclerosis. It modifies the body composition at diagnosis, and patients with hypermetabolism >20% have a worse prognosis than those without hypermetabolism.

ALS and frontotemporal dementia belong to a common disease spectrum.

ALS is now understood to be a complex multisystem neurodegenerative disease because areas other than the motor cortices of the brain undergo degeneration. Frontotemporal dementia (FTD) may be associated with motor neuron disease, and the transactive response DNA-binding protein 43 (TDP-43) is a major pathological substrate underlying both diseases. The recent discovery of a gene that can cause both FTD, ALS and FTD-ALS, C9ORF72, has modified the way for considering these two pathologies. These findings would allow the development of potential biomarkers and therapeutic targets for these devastating diseases. This review summarizes the key points leading up to our current understanding of the genetic, clinical and neuropathological overlap between FTD and ALS.

Epidemiology of amyotrophic lateral sclerosis: A review of literature.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, resulting in worsening weakness of voluntary muscles until death occurs from respiratory failure. The incidence of ALS in European populations is two to three people per year per 100,000 of the general population. In Europe, crude prevalences range from 1.1/100,000 population in Yugoslavia to 8.2/100,000 in the Faroe Islands. Major advances have been made in our understanding of the genetic causes of ALS, whereas the contribution of environmental factors has been more difficult to assess and large-scale studies have not yet revealed a replicable, definitive environmental risk factor. The only established risk factors to date are older age, male gender and a family history of ALS. Median survival time from onset to death is usually 3 years from the first appearance of symptoms. Older age and bulbar onset are consistently reported to have poorer outcomes. However, there are conflicting data regarding gender, diagnostic delay and El Escorial criteria. The rate of symptom progression has been revealed to be an independent prognostic factor. Psychosocial factors and impaired cognitive function are negatively related to ALS outcome, while nutritional status and respiratory function are also related to ALS prognosis. The effect of enteral nutrition on survival is still unclear, although noninvasive positive pressure ventilation (NIPPV) has been found to improve survival. These findings have relevant implications for the design of future trials.

Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study.

Respiratory disease is the predominant cause of illness in children globally. We describe a unique multidisciplinary South African birth cohort, the Drakenstein Child Health Study (DCHS), to investigate the incidence, risk factors, aetiology and long-term impact of early lower respiratory tract infection (LRTI) on child health. Pregnant women from a poor, peri-urban community with high exposure to infectious diseases and environmental risk factors are enrolled with 1000 mother-child pairs followed for at least 5 years. Biomedical, environmental, psychosocial and demographic risk factors are longitudinally measured. Environmental exposures are measured using monitors placed at home visits. Lung function is measured in children at 6 weeks, annually and during LRTI episodes. Microbiological investigations including microbiome and multiplex PCR measures are done longitudinally and at LRTI episodes. The DCHS is a unique African birth cohort study that uses sophisticated measures to comprehensively investigate the early-life determinants of child health in an impoverished area of the world.

Population-based epidemiology of amyotrophic lateral sclerosis (ALS) in an ageing Europe--the French register of ALS in Limousin (FRALim register).

BACKGROUND AND PURPOSE: The main objective of establishing the French register of amyotrophic lateral sclerosis (ALS) in the Limousin region (FRALim), was to assess the incidence of ALS, in this ageing region of Europe, over a 12-year period (2000-2011). METHODS: Patients were included if they lived in Limousin at the time of diagnosis of ALS according to El Escorial revised criteria and were identified by at least one of the following sources: (i) the French national body coordinating ALS referral centres; (ii) public and private hospitals in the region; (iii) health insurance data related to long-term diseases. RESULTS: The FRALim register identified 279 incident cases (2000-2011). The crude and European population standardized incidences of ALS were as high as 3.19/100,000 person-years of follow-up (95% CI 2.81-3.56) and 2.58/100,000 person-years of follow-up (95% CI 2.27-2.89) respectively. Median age at onset was 70.8 years (interquartile range 63.1-77.1). The standardized sex incidence ratio (male/female) was 1.3 overall, but 1.1 under the age of 65 years, 1.7 between 65 and 75 years and 1.9 above 75 years. The exhaustiveness of the register has been estimated at 98.4% (95% CI 95.6-99.4) by capture-recapture analysis. CONCLUSION: It was possible for the first time in France to monitor accurately the incidence of ALS over a long time period. It appears to be in the upper range of data reported in western countries. Patterns displayed here might anticipate the epidemiology of ALS in ageing western countries.

Reflex Xpert MTB/XDR Testing of Residual Rifampicin-Resistant Specimens: A Clinical Laboratory-Based Diagnostic Accuracy and Feasibility Study in South Africa.

Background: The World Health Organization-approved Xpert MTB/XDR test detects Mycobacterium tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and injectable drugs directly in specimens. This pragmatic, laboratory-based study assessed the diagnostic accuracy and feasibility of a reflex testing approach, where Xpert MTB/XDR was performed on residual specimens previously processed for Xpert MTB/RIF Ultra. Methods: Routine respiratory specimens, processed for Xpert MTB/RIF Ultra, were stored in sample reagent buffer at 2°C-8°C. If rifampicin resistant, the residual specimen was assessed for adequate volume (≥2 mL) and tested with Xpert MTB/XDR, with storage time recorded. A second specimen was used for routine and reference standard testing (culture and sequencing). Results: Specimens (99% sputum) from 763 participants submitted to 2 large routine laboratories were included. Xpert MTB/XDR yielded valid resistance detection results in 639 (84%), compared with 507 (66%) for routine testing (difference [95% CI], 18% [13%-22%]). The median turnaround time for results was 23 hours for Xpert MTB/XDR and 15 days for routine testing. While 748 specimens (98%) were ≥2 mL, only 102 (13%) were stored for ≤4 hours. By the reference standard, 284 of 394 (72%) were isoniazid resistant, and 57 of 380 (15%) were fluroquinolone resistant. The sensitivities of Xpert MTB/XDR were 94% (95% CI, 91%-97%) for isoniazid and 91% (81%-97%) for fluoroquinolone resistance detection. The specificities were 98% (94%-100%) and 100% (98%-100%), respectively. Conclusions: Xpert MTB/XDR performed favorably compared with the reference, and the reflex testing approach increased results availability over routine testing, while dramatically decreasing turnaround time from weeks to hours. Laboratory workflow precluded testing within the manufacturer-recommended 4-hour storage time, but longer storage did not appear detrimental.

Primary cheilorhinoseptoplasty using the Talmant protocol in unilateral complete cleft lip: functional and aesthetic results on nasal correction and comparison with the Tennison-Malek protocol.

Many surgical procedures used to treat patients with unilateral complete cleft lip do not include a complete primary rhinoseptoplasty, which is delayed until the end of growth as part of secondary surgery. Primary cheilorhinoseptoplasty using the Talmant technique has been performed at Lapeyronie University Hospital, Montpellier for 15 years. This retrospective study evaluated and compared the functional and aesthetic results obtained in such patients at 4-6 years after surgery with those obtained without primary rhinoseptoplasty in patients undergoing the Tennison-Malek technique. This study included a cohort of 60 children who presented a unilateral complete cleft lip: 29 were operated on with the Tennison-Malek technique and 31 with the Talmant technique. Three functional and 14 aesthetic criteria were evaluated. All functional criteria showed better results in the Talmant group: nocturnal nasal breathing (P < 0.001), incidence of closed rhinolalia (P = 0.0019), and presence of asymmetric nasal breathing (P < 0.001). Concerning the aesthetic results, all criteria evaluated on the frontal and basal photographs of each patient showed significantly better results in the Talmant technique group. The rate of satisfactory results was> 75% for 12 of the 14 criteria in the Talmant group, compared with none of the 14 criteria in the Tennison-Malek group.

Alteration of nutritional status at diagnosis is a prognostic factor for survival of amyotrophic lateral sclerosis patients.

OBJECTIVES: The aims were to analyse changes in nutritional parameters from diagnosis of amyotrophic lateral sclerosis (ALS) to death and to assess their relationships with survival at the time of diagnosis and during follow-up. METHODS: 92 ALS patients were included and clinically assessed every 3 months (ALS functional rating scale, manual muscular testing, forced vital capacity, weight, BMI, percentage weight loss). Bioimpedance was performed to evaluate body composition (fat-free mass, fat mass and hydration status) and phase angle. Survival analyses were performed from diagnosis to death or censoring date using a Cox model. RESULTS: The evolution of nutritional parameters in ALS patients was marked by significant decreases in weight, BMI, fat-free mass and phase angle, and increased fat mass. The authors identified an adjusted 30% increased risk of death for a 5% decrease from usual weight at time of diagnosis (RR 1.30; 95% CI 1.08 to 1.56). During follow-up, the authors identified adjusted 34% (95% CI 18% to 51%) and 24% (95% CI 13% to 36%) increased risks of death associated with each 5% decrease in usual weight and each unit decrease in usual BMI, respectively (p<0.0001). Malnutrition during the course was related to a shorter survival (p=0.01), and fat mass level was associated with a better outcome (RR 0.90 for each 2.5 kg fat mass increment). CONCLUSIONS: Nutritional parameters of ALS patients worsened during evolution of the disease, and worse nutritional status (at time of diagnosis or during the course) was associated with a higher mortality. This study offers some justification for studying the use of therapeutic nutritional intervention to modify the survival of ALS patients.

Lithium hydroxide dihydrate: a new type of icy material at elevated pressure.

We show that, in addition to the known monohydrate, LiOH forms a dihydrate at elevated pressure. The dihydrate involves a large number of H-bonds establishing chains along the <001> direction. In addition, the energy surface exhibits a saddle point for proton locations along certain O interatomic distances, a feature characteristic for superprotonic conductors. However, MD simulations indicate that LiOH · 2H(2)O is not a superprotonic conductor and suggest the relevant interpolyhedral O-O distances being too large to allow for proton transfer between neighboring Li-coordinated polyhedra at least on the time scale of the MD-simulations.

Diverse clinical and social circumstances: developing patient-centred care for DR-TB patients in South Africa.

OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.

OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

Developmental, Morphological and Physiological Traits in Plants Exposed for Five Generations to Chronic Low-Level Ionising Radiation.

The effects of ionising radiation (IR) on plants are important for environmental protection but also in agriculture, horticulture, space science, and plant stress biology. Much current understanding of the effects of IR on plants derives from acute high-dose studies but exposure to IR in the environment frequently occurs at chronic low dose rates. Chronic low dose-rate studies have primarily been field based and examined genetic or cytogenetic endpoints. Here we report research that investigated developmental, morphological and physiological effects of IR on Arabidopsis thaliana grown over 7 generations and exposed for five generations to chronic low doses of either 137Cs (at a dose rate of c. 40 µGy/h from ß/γ emissions) or 10 µM CdCl2. In some generations there were significant differences between treatments in the timing of key developmental phases and in leaf area or symmetry but there were, on the basis of the chosen endpoints, no long-term effects of the different treatments. Occasional measurements also detected no effects on root growth, seed germination rates or redox poise but in the generation in which it was measured exposure to IR did decrease DNA-methylation significantly. The results are consistent with the suggestion that chronic exposure to c. 40 µGy/h can have some effects on some traits but that this does not affect function across multiple generations at the population level. This is explained by the redundancy and/or degeneracy between biological levels of organization in plants that produces a relatively loose association between genotype and phenotype. The importance of this explanation to understanding plant responses to stressors such as IR is discussed. We suggest that the data reported here provide increased confidence in the Derived Consideration Reference Levels (DCRLs) recommended by the International Commission for Radiological Protection (ICRP) by providing data from controlled conditions and helping to contextualize effects reported from field studies. The differing sensitivity of plants to IR is not well understood and further investigation of it would likely improve the use of DCRLs for radiological protection.

Drug-resistant tuberculosis patient care journeys in South Africa: a pilot study using routine laboratory data.

SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.

Diagnosis and management of community-acquired pneumonia in children: South African Thoracic Society guidelines.

BACKGROUND: Pneumonia remains a major cause of morbidity and mortality amongst South African children. More comprehensive immunisation regimens, strengthening of HIV programmes, improvement in socioeconomic conditions and new preventive strategies have impacted on the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis. OBJECTIVES: To produce revised guidelines for pneumonia in South African children under 5 years of age. METHODS: The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases established seven expert subgroups to revise existing South African guidelines focusing on: (i) epidemiology; (ii) aetiology; (iii) diagnosis; (iv) antibiotic management and supportive therapy; (v) management in intensive care; (vi) prevention; and (vii) considerations in HIV-infected or HIVexposed, uninfected (HEU) children. Each subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system. Sections were synthesized into an overall guideline which underwent peer review and revision. RECOMMENDATIONS: Recommendations include a diagnostic approach, investigations, management and preventive strategies. Specific recommendations for HIV infected and HEU children are provided. VALIDATION: The guideline is based on available published evidence supplemented by the consensus opinion of SA paediatric experts. Recommendations are consistent with those in published international guidelines.

The nature of the interior of uranus based on studies of planetary ices at high dynamic pressure.

Data from the Voyager II spacecraft showed that Uranus has a large magnetic field with geometry similar to an offset tilted dipole. To interpret the origin of the magnetic field, measurements were made of electrical conductivity and equation-of-state data of the planetary "ices" ammonia, methane, and "synthetic Uranus" at shock pressures and temperatures up to 75 gigapascals and 5000 K. These pressures and temperatures correspond to conditions at the depths at which the surface magnetic field is generated. Above 40 gigapascals the conductivities of synthetic Uranus, water, and ammonia plateau at about 20(ohm-cm)(-1), providing an upper limit for the electrical conductivity used in kinematic or dynamo calculations. The nature of materials at the extreme conditions in the interior is discussed.

What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss.

Life skills programmes for chronic mental illnesses.

BACKGROUND: Most people with schizophrenia have a cyclical pattern of illness characterised by remission and relapses. The illness can reduce the ability of self-care and functioning and can lead to the illness becoming chronic and disabling. Rehabilitation is one of the important parts of treatments. Life skills programmes, emphasising the needs associated with independent functioning, are often a part of the rehabilitation process. These programmes, therefore, have been developed to enhance independent living and the quality of life for people with schizophrenia living in the community. OBJECTIVES: To review the effectiveness of life skills programmes with standard care or other comparable therapies for people with chronic mental health problems. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (May 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Hand searches and scrutiny of references supplemented this process. We inspected references of all identified studies for further trials. SELECTION CRITERIA: We included all relevant randomised or quasi-randomised controlled trials for life skills programmes versus other comparable therapies or standard care involving people with serious mental illnesses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. MAIN RESULTS: We included four randomised controlled trials with a total of 318 participants. These evaluated life skills programmes versus standard care, or support group. We found no significant difference in life skills performance between people given life skills training and standard care (Patterson 2003, n=32, WMD -1.10 CI -7.8 to 5.6). Life skills training did not improve or worsen study retention (n=60, 2 RCTs, RR 1.16 CI 0.4 to 3.4). We found no significant difference in PANSS positive, negative or total scores between life skills intervention and standard care. Depression scores (HAM-D) did not reveal any significant difference between groups (Patterson 2003, n=32, WMD -0.70 CI -4.1 to 2.7). We found quality of life scores to be equivocal between participants given life skills training (Patterson 2003, n=32, WMD -0.02 CI -0.1 to 0.03) and standard care. Life skills compared with support groups also did not reveal any significant differences in PANSS scores, quality of life, or social performance skills (Patterson 2006, n=158, WMD -0.90 CI -3.4 to 1.6). AUTHORS' CONCLUSIONS: Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems.

Fluctuating asymmetry of the normal facial skeleton.

The purpose of this study was to produce reliable estimations of fluctuating facial asymmetry in a normal population. Fifty-four computed tomography (CT) facial models of average-looking and symmetrical Chinese subjects with a class I occlusion were used in this study. Eleven midline landmarks and 12 pairs of bilateral landmarks were digitized. The repeatability of the landmark digitization was first evaluated. A Procrustes analysis was then used to measure the fluctuating asymmetry of each CT model, after all of the models had been scaled to the average face size of the study sample. A principal component analysis was finally used to establish the direction of the fluctuating asymmetries. The results showed that there was excellent absolute agreement among the three repeated measurements. The mean fluctuating asymmetry of the average-size face varied at each anthropometric landmark site, ranging from 1.0mm to 2.8mm. At the 95% upper limit, the asymmetries ranged from 2.2mm to 5.7mm. Most of the asymmetry of the midline structures was mediolateral, while the asymmetry of the bilateral landmarks was more equally distributed. These values are for the average face. People with larger faces will have higher values, while subjects with smaller faces will have lower values.