Requirements for ethics committee review for studies submitted to Implementation Science

The requirement for ethics review of studies submitted to Implementation Science has been unclear. Therefore, in this editorial, we set out our requirements for ethics committee review of experimental and non-experimental studies. For any study that meets the criteria of human subject research (which includes research on healthcare providers), irrespective of study design, we will require proof of either satisfactory ethics committee review or of the granting of an official exemption or waiver

Under-five mortality: spatial-temporal clusters in Ifakara HDSS in South-eastern Tanzania.

BACKGROUND\ud \ud Childhood mortality remains an important subject, particularly in sub-Saharan Africa where levels are still unacceptably high. To achieve the set Millennium Development Goals 4, calls for comprehensive application of the proven cost-effective interventions. Understanding spatial clustering of childhood mortality can provide a guide in targeting the interventions in a more strategic approach to the population where mortality is highest and the interventions are most likely to make an impact.\ud \ud METHODS\ud \ud Annual child mortality rates were calculated for each village, using person-years observed as the denominator. Kulldorff's spatial scan statistic was used for the identification and testing of childhood mortality clusters. All under-five deaths that occurred within a 10-year period from 1997 to 2006 were included in the analysis. Villages were used as units of clusters; all 25 health and demographic surveillance sites (HDSS) villages in the Ifakara health and demographic surveillance area were included.\ud \ud RESULTS\ud \ud Of the 10 years of analysis, statistically significant spatial clustering was identified in only 2 years (1998 and 2001). In 1998, the statistically significant cluster (p < 0.01) was composed of nine villages. A total of 106 childhood deaths were observed against an expected 77.3. The other statistically significant cluster (p < 0.05) identified in 2001 was composed of only one village. In this cluster, 36 childhood deaths were observed compared to 20.3 expected. Purely temporal analysis indicated that the year 2003 was a significant cluster (p < 0.05). Total deaths were 393 and expected were 335.8. Spatial-temporal analysis showed that nine villages were identified as statistically significant clusters (p < 0.05) for the period covering January 1997-December 1998. Total observed deaths in this cluster were 205 while 150.7 were expected.\ud \ud CONCLUSION\ud \ud There is evidence of spatial clustering in childhood mortality within the Ifakara HDSS. Further investigations are needed to explore the source of clustering and identify strategies of reaching the cluster population with the existing effective interventions. However, that should happen alongside delivery of interventions to the broader population

The Pigna Barney Ophiolitic Complex and Associated Basaltic Rocks, Northeastern New South Wales, Australia

The Pigna Barney Ophiolitic Complex (PBOC) is a lithologically and chemically distinctive ultramafic-mafic melange which is largely confined to major fault zones in the Pigna Barney-Curricabark area, southern New England Orogen (NEO), northeastern New South Wales. For the most part, the PBOC lies along the arcuate, southern-most section of the Peel Fault System. This major steeply-dipping fault system marks the line of contact between a complex accretionary terrane (Zone B) lying to the east and north, and a significantly less-deformed volcanic arcrelated basin (Tamworth Belt) lying to the west and south. Fragments of the PBOC also lie within Zone B, especially along the Curricabark Fault Zone and along faulted contacts between the? pre-Devonian, largely hemipelagic Myra beds and Permian epiclastics of the Nambucca Association. The PBOC is everywhere in contact with adjacent stratigraphic associations, and non-tectonic contacts between its various component lithologies are exceedingly rare. The PBOC consists of: (i) a highly disrupted and incompletely preserved ophiolitic assemblage whose members consistently display atypically low abundances of "incompatible" elements (e.g. Ti, Zr, P); and (ii) a diverse range of igneous, sedimentary and metamorphic lithologies which generally occur as tectonic blocks in serpentinite-matrix melange (highly sheared tectonized harzburgite). In its type area the PBOC displays a crude internal ophiolitic stratigraphy which, at least on present orientation, consistently faces the Tamworth Belt to the southwest. Seven distinct lithological groups comprise the ophiolitic members of the PBOC. All groups are altered to varying degrees. In order of general structural position and inferred stratigraphic sequence these groups are: (1) depleted tectonized harzburgite - Fo92-91,Al₂0

Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Molecular diversity of anthracnose pathogen populations associated with UK strawberry production suggests multiple introductions of three different Colletotrichum species.

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production

Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania.

Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild-type (β-coefficient -16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35-0·8] & RRR = 0·43 [95% CI:0·23-0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17-0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha-thalassaemia in reducing risk of abnormal CBFv

The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope

Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been detected, and numerous models proposed to explain their occurrence, they have remained enigmatic owing to the lack of an obvious counterpart at other wavelengths. The recent ground-based detection of a transient source in the vicinity of GRB 970228 may therefore have provided a breakthrough. The optical counterpart appears to be embedded in an extended source which, if a galaxy as has been suggested, would lend weight to those models that place GRBs at cosmological distances. Here we report the observations using the Hubble Space Telescope of the transient counterpart and extended source 26 and 39 days after the initial gamma-ray outburst. We find that the counterpart has faded since the initial detection (and continues to fade), but the extended source exhibits no significant change in brightness between the two dates of observations reported here. The size and apparent constancy between the two epochs of HST observations imply that it is extragalactic, but its faintness makes a definitive statement about its nature difficult. Nevertheless, the decay profile of the transient source is consistent with a popular impulsive-fireball model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue

Extrapontine myelinolysis presenting as acute parkinsonism

BACKGROUND: Extrapontine myelinolysis presenting with extra pyramidal features suggestive of parkinsonism may be a challenging clinical syndrome. Clinicians should maintain their vigilance while correcting electrolyte imbalances, especially with associated co-morbidity. CASE PRESENTATION: A 41-year-old woman presented with acute parkinsonism like features while on a holiday. This followed slow correction of hyponatraemia after repeated vomiting. MRI changes were suggestive of Extrapontine myelinolysis(EPM). This case is at variance with four previous cases reported in the medical literature in that the patient made a full clinical recovery and the MR changes resolved with symptomatic support alone. CONCLUSION: Extrapontine myelinolysis could make a complete recovery with symptomatic support alone. During hyponatraemia correction, rapid osmotic shifts of fluid that cause hypernatremia, causes myelinolysis rather than absolute serum sodium level. Even gradual correction of hyponatraemia can produce myelinolysis, especially with pre-existing malnourishment, alcoholism, drug misuse, Addison's disease and immuno-suppression. Pallidial sparing is typical of EPM in MRI scans

Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion. In the current study, we demonstrate that virally expressed integrins (α9, α6, or β1 integrin) in the adult rat sensorimotor cortex and adult red nucleus are excluded from axons following neuronal transduction. Attempts to stimulate transport by inclusion of a cervical spinal injury and thus an upregulation of extracellular matrix molecules at the lesion site, or cotransduction with its binding partner, β1 integrin, did not induce integrin localization within axons. In contrast, virally expressed α9 integrin in developing rat cortex (postnatal day 5 or 10) demonstrated clear localization of integrins in cortical axons revealed by the presence of integrin in the axons of the corpus callosum and internal capsule, as well as in the neuronal cell body. Furthermore, examination of dorsal root ganglia neurons and retinal ganglion cells demonstrated integrin localization both within peripheral nerve as well as dorsal root axons and within optic nerve axons, respectively. Together, our results suggest a differential ability for in vivo axonal transport of transmembrane proteins dependent on neuronal age and subtype

Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580