Associations between presence of handwashing stations and soap in the home and diarrhoea and respiratory illness, in children less than five years old in rural western Kenya.

OBJECTIVE: We tested whether soap presence in the home or a designated handwashing station was associated with diarrhoea and respiratory illness in Kenya. METHODS: In April 2009, we observed presence of a handwashing station and soap in households participating in a longitudinal health surveillance system in rural Kenya. Diarrhoea and acute respiratory illness (ARI) in children < 5 years old were identified using parent-reported syndromic surveillance collected January-April 2009. We used multivariate generalised linear regression to estimate differences in prevalence of illness between households with and without the presence of soap in the home and a handwashing station. RESULTS: Among 2547 children, prevalence of diarrhoea and ARI was 2.3 and 11.4 days per 100 child-days, respectively. Soap was observed in 97% of households. Children in households with soap had 1.3 fewer days of diarrhoea/100 child-days (95% CI -2.6, -0.1) than children in households without soap. ARI prevalence was not associated with presence of soap. A handwashing station was identified in 1.4% of households and was not associated with a difference in diarrhoea or ARI prevalence. CONCLUSIONS: Soap presence in the home was significantly associated with reduced diarrhoea, but not ARI, in children in rural western Kenya. Whereas most households had soap in the home, almost none had a designated handwashing station, which may prevent handwashing at key times of hand contamination.

The dangers of the day of birth.

OBJECTIVE: To compare the risk of fetal death on the day of childbirth, with the risk of death at other ages, and with the risks of some hazardous activities, on a common scale of risk per day. DESIGN: Review of publicly available data. SETTING UK SAMPLE: Data extracted from the Office of National Statistics and other sources. METHODS: Data from the Office of National Statistics and other sources were used to calculate death rates at different ages expressed as rates per day of life. Death rates for different activities were also calculated as risks per day, or risks per activity, as appropriate. All risks were expressed in micromorts, the number of one in a million chances of dying. Figures on life expectancy (LE) were used to compare potential life years lost. MAIN OUTCOME MEASURES: Daily, or unit of activity, risk of dying for different activities compared with the risk of dying on the day of childbirth. RESULTS: The risk of dying on the day of birth (0.43 per 1000, or 430 micromorts) exceeds that of any other average day of life until the 92nd year. It is comparable with other apparently more dangerous activities, such as undergoing major surgery. For comparison, the average risk of non-natural death per day and the increased risk from smoking one cigarette or travelling 200 miles by car are all about 1 micromort. CONCLUSIONS: The lifetime risk of death in childbirth is low, but is concentrated in a short period, making being born a high-risk activity. Parents considering interventions to reduce these risks should be made aware of this.

A genomic approach to predict synergistic combinations for breast cancer treatment.

We leverage genomic and biochemical data to identify synergistic drug regimens for breast cancer. In order to study the mechanism of the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) in breast cancer, we generated and validated genomic profiles of drug response using a series of breast cancer cell lines sensitive to each drug. These genomic profiles were then used to model drug response in human breast tumors and show significant correlation between VPA and SAHA response profiles in multiple breast tumor data sets, highlighting their similar mechanism of action. The genes deregulated by VPA and SAHA converge on the cell cycle pathway (Bayes factor 5.21 and 5.94, respectively; P-value 10(-8.6) and 10(-9), respectively). In particular, VPA and SAHA upregulate key cyclin-dependent kinase (CDK) inhibitors. In two independent datasets, cancer cells treated with CDK inhibitors have similar gene expression profile changes to the cellular response to HDAC inhibitors. Together, these results led us to hypothesize that VPA and SAHA may interact synergistically with CDK inhibitors such as PD-033299. Experiments show that HDAC and CDK inhibitors have statistically significant synergy in both breast cancer cell lines and primary 3-dimensional cultures of cells from pleural effusions of patients. Therefore, synergistic relationships between HDAC and CDK inhibitors may provide an effective combinatorial regimen for breast cancer. Importantly, these studies provide an example of how genomic analysis of drug-response profiles can be used to design rational drug combinations for cancer treatment.

Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006 to 2034: A transmission modeling analysis.

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.

Factors associated with missed and delayed DTP3 vaccination in children aged 12 - 59 months in two communities in South Africa, 2012 - 2013.

BACKGROUND: Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting. OBJECTIVES: To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12 - 59 months in two SA communities. METHODS: We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged <5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression. RESULTS: Of a total of 847 eligible children aged 12 - 59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7 - 23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4 - 6.3) or 2011 (aOR 2.7, 95% CI 1.3 - 5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3 - 0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6 - 7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged <5 years in a household (aOR 2.4, 95% CI 1.2 - 4.9) compared with one child, and household monthly income <ZAR500 (aOR 3.4, 95% CI 1.1 - 11.4) compared with ≥ZAR2 000. CONCLUSIONS: Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination.

Healthcare utilisation patterns for respiratory and gastrointestinal syndromes and meningitis in Msunduzi municipality, Pietermaritzburg, KwaZulu-Natal Province, South Africa, 2013.

BACKGROUND: Public health facilities are used by the majority of South Africans, and healthcare utilisation surveys have been a useful tool to estimate the burden of disease in a given area. OBJECTIVES: To describe care-seeking behaviour in a periurban site with a high prevalence of HIV infection, as well as barriers to seeking appropriate healthcare. METHODS: We conducted a cross-sectional household survey in 22 wards of the Msunduzi municipality in KwaZulu-Natal Province, South Africa, from October to December 2013 using a simple random sample of households selected from a 2011 census enumeration. A primary caregiver/adult decision-maker was interviewed regarding demographic data as well as health status and recent self-reported episodes of selected illnesses and healthcare utilisation. RESULTS: Of the 2 238 eligible premises visited, 1 936 households (87%) with a total of 9 733 members were enrolled in the study. Of these, 635 (7%) reported one or more episodes of infectious illness during the study period. Public health clinics were most frequently consulted for all illnesses (361/635, 57%). Private healthcare (general practitioner, private clinic, private hospital) was sought by 90/635 of individuals (14%), only 13/635 (2%) reported seeking care from traditional healers, religious leaders or volunteers, and 71/635 (11%) did not seek any medical care for acute illnesses. Individuals in the lowest income group were more likely to seek care at public health facilities than those in the highest income group (70% v. 32%). CONCLUSIONS: Public health facility-based surveillance may be representative of disease patterns in this community, although surveillance at household level shows that high-income individuals may be excluded because they were more likely to use private healthcare, and the proportion of individuals who died at home would have been missed by facility-based surveillance. Data obtained in such surveys may be useful for public health planning.

Genome Sequence of Euphorbia mosaic virus from Passionfruit and Euphorbia heterophylla in Florida.

Euphorbia mosaic virus (EuMV) was found in a symptomatic passionfruit (Passiflora edulis) plant from Homestead, Florida, USA, as well as in the symptomatic weed Euphorbia heterophylla This is the first identification of EuMV in Florida and the United States and the first report of a natural infection of passionfruit by EuMV.

Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice.

Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.

An exemplar-retrieval model of speeded same--different judgments.

R. M. Nosofsky and T. J. Palmeri's (1997) exemplar-based random-walk (EBRW) model of speeded classification is extended to account for speeded same--different judgments among integral-dimension stimuli. According to the model, an important component process of same--different judgments is that people store individual examples of experienced same and different pairs of objects in memory. These exemplar pairs are retrieved from memory on the basis of how similar they are to a currently presented pair of objects. The retrieved pairs drive a random-walk process for making same--different decisions. The EBRW predicts correctly that same responses are faster for objects lying in isolated than in dense regions of similarity space. The model also predicts correctly effects of same-identity versus same-category instructions and is sensitive to observers' past experiences with specific same and different pairs of objects.

A case-control study of late recurrence of malignant melanoma.

Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.

Benign recurrent intrahepatic cholestasis (Summerskill and Walshe syndrome). Case report and revision of bibliography.

We describe the case of a 58-year old woman who had four episodes of choluric jaundice and severe pruritus, starting at age 48. Each episode lasted about four months and had a spontaneous remission. During icteric episodes, conjugated bilirubinemia, alkaline phosphatase, and to a lower degree transaminases, were increased; white cell count was higher and there was a marked rise in sedimentation rate. Between such episodes there was a complete clinical remission, and laboratory alterations returned to normal, although sometimes a high alkaline phosphatase persisted. There was no history of previous drug intake known to produce these disorders. During the last icteric episode, an exploratory laparatomy, with roentgenographic study was done, which demonstrated that the extrahepatic biliary tract was intact. Histology revealed that the liver showed a preserved, regular architecture, of which the salient feature was intrahepatic cholestasis. Corticoids and cholestyramine were of little benefit for pruritus.

Supporting new vaccine introduction decisions: lessons learned from the Hib Initiative experience.

The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines.

Diffractive bifocal lens designs.

Modifying the number, width, depth, and shape of the echelettes in a diffractive bifocal lens will influence the image intensity and quality within the zero, first, and higher order images. By appropriately varying these parameters optimal bifocal lens designs may be achieved.

Practical design of a bifocal hologram contact lens or intraocular lens.

When designing diffractive lenses, a high-diffraction efficiency at a particular design wavelength is often the most important criterion. Recently it has become of interest to consider lens designs that split incident light predominantly into two orders for use as bifocal contact lenses or intraocular lenses. Surface- relief profiles on contact and intraocular lenses are subject to many practical constraints in addition to requiring high efficiencies at the two focal points. A new lens design combining a binary-amplitude absorption profile with a unique nonparabolic surface-relief profile is proposed to satisfy these constraints.

Role of gravity in prism ballasting.

One of the techniques commonly used in stabilizing the rotation of a contact lens is prism ballasting. The idea is to gain stabilization by the action of gravity pulling on the base of the prism. The determination of just how much prism is necessary in any particular case is usually made empirically, gradually increasing prism amount when more stability is required. This paper will present the results of a mathematical investigation which demonstrates that gravity forces alone do not play the major role in the stabilization of prism ballasted lenses. It is hoped that this preliminary analysis will stimulate further theoretical work of a similar nature, in the growing field of contact lenses.

Critical point drying: contamination in transitional fluid supply cylinders.

We call attention to the occurrence of an oily residue in the CPD bomb after critical point drying, as well as the presence of rust, dirt, and an oily residue in CO2 and Freon supply cylinders. Bottled gas is often tested for purity once after manufacturing and then is pumped and stored, perhaps several times, before the consumer's cylinders are filled. The cylinders may be in use for over 40 years, and may never be chemically cleaned, although they are hydrostatically pressure tested every five years, with the date of each test stamped on the cylinder. To the bottled gas industry we recommend regular inspection of tanks for bottom contamination, and vacuum and chemical cleaning when contamination is found. To users of bottled gas for critical point drying, we recommend becoming aware of the procedures of cylinder inspection, cleaning, and circulation among users. We suggest reporting to the gas supplier any contamination produced by inadvertently backfilling the supply cylinder. Although a common awareness of the problem of supply cylinder residues should lead to failures, the best assurance of clean, oil-free, dry liquid CO2 and other transitional fluids may be in the development of in-line filters which would remove particles, oil and moisture between the supply cylinder and the CPD bomb. We also suggest the use of gas grades higher than commercial, such as welding anhydrous (CO2) or specialty gases.

Purification, quaternary structure, composition, and properties of D-ribulose-1,5-bisphosphate carboxylase from Thiobacillus intermedius.

D-Ribulose-1,5-bisphosphate (RuBP) carboxylase has been purified from glutamate-CO2-S2O3(2)-grown Thiobacillus intermedius by pelleting the enzyme from the high-speed supernatant and by intermediary crystallization followed by sedimentation into a discontinuous 0.2 to 0.8 M sucrose gradient. The enzyme was homogeneous by the criteria of electrophoresis on polyacrylamide gels of several acrylamide concentrations, sedimentation velocity and equilibrium measurements, and electron microscopic observations of negatively stained preparations. The molecular weights of the enzyme determined by sedimentation equilibrium and light-scattering measurements averaged 462,500 +/- 13,000. The enzyme consisted of closely similar or identical polypeptide chains of a molecular weight of 54,500 +/- 5,450 determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The S(0)20,w of the enzyme was 18.07S +/- 0.22. Electron microscopic examination suggested that the octomeric enzyme (inferred from the molecular measurements mentioned) had a cubical structure. The specific activity of the enzyme was 2.76 mumol of RuBP-dependent CO2 fixed/min per mg of protein (at pH 8 and 30 C), and the turnover number in terms of moles of CO2 fixed per mole of catalytic site per second was 2.6. The enzyme was stable for 3 months at -20 C and at least 4 weeks at 0 C. The apparent Km for CO2 was 0.75 mM, and Km values for RuBP and Mg2+ were 0.076 and 3.6 mM, respectively. Dialyzed enzyme could be fully reactivated by the addition of 20 mM Mg2+ and partially reactivated by 20 mM Co2+, but Cd2+, Mn2+, Ca2+, and Zn2+ had no effect. The compound 6-phosphogluconate was a linear competitive inhibitor with respect to RuBP when it had been preincubated with enzyme, Mg2+, and HCO3-.

Category variability, exemplar similarity, and perceptual classification.

Experiments were conducted in which observers learned to classify simple perceptual stimuli into low-variability and high-variability categories. Similarities between objects were measured in independent psychological-scaling tasks. The results showed that observers classified transfer stimuli into the high-variability categories with greater probability than was predicted by a baseline version of an exemplar-similarity model. Qualitative evidence for the role of category variability on perceptual classification, which could not be explained in terms of the baseline exemplar-similarity model, was obtained as well. Possible accounts of the effects of category variability are considered in the General Discussion section.