Spatial model for risk prediction and sub-national prioritization to aid poliovirus eradication in Pakistan.

BACKGROUND: Pakistan is one of only three countries where poliovirus circulation remains endemic. For the Pakistan Polio Eradication Program, identifying high risk districts is essential to target interventions and allocate limited resources. METHODS: Using a hierarchical Bayesian framework we developed a spatial Poisson hurdle model to jointly model the probability of one or more paralytic polio cases, and the number of cases that would be detected in the event of an outbreak. Rates of underimmunization, routine immunization, and population immunity, as well as seasonality and a history of cases were used to project future risk of cases. RESULTS: The expected number of cases in each district in a 6-month period was predicted using indicators from the previous 6-months and the estimated coefficients from the model. The model achieves an average of 90% predictive accuracy as measured by area under the receiver operating characteristic (ROC) curve, for the past 3 years of cases. CONCLUSIONS: The risk of poliovirus has decreased dramatically in many of the key reservoir areas in Pakistan. The results of this model have been used to prioritize sub-national areas in Pakistan to receive additional immunization activities, additional monitoring, or other special interventions.

Scenario processes for socio-environmental systems analysis of futures: A review of recent efforts and a salient research agenda for supporting decision making.

This paper reviews the latest research on scenarios including the processes and products for socio-environmental systems (SES) analysis, modeling and decision making. A group of scenario researchers and practitioners participated in a workshop to discuss consolidation of existing research on the development and use of scenario analysis in exploring and understanding the interplay between human and environmental systems. This paper presents an extended overview of the workshop discussions and follow-up review work. It is structured around the essential challenges that are crucial to progress support of decision making and learning with respect to our highly uncertain socio-environmental futures. It identifies a practical research agenda where challenges are grouped according to the process stage at which they are most significant: before, during, and after the creation of the scenarios as products. These challenges for SES include: enhancing the role of stakeholder and public engagement in the co-development of scenarios, linking scenarios across multiple geographical, sectoral and temporal scales, improving the links between the qualitative and quantitative aspects of scenario analysis, addressing uncertainties especially surprise, addressing scenario diversity and their consistency together, communicating scenarios including visualization methods, and linking scenarios to decision making.

Shigella dysenteriae serotype 1 in west Africa: intervention strategy for an outbreak in Sierra Leone.

In November 1999, a Médecins Sans Frontières team based in the southeastern part of Sierra Leone reported an increased number of cases of bloody diarrhoea. Shigella dysenteriae serotype 1 (Sd1) was isolated in the early cases. A total of 4218 cases of dysentery were reported in Kenema district from December, 1999, to March, 2000. The overall attack rate was 7.5%. The attack rate was higher among children younger than 5 years than in the rest of the population (11.2% vs 6.8%; relative risk=1.6; 95% CI 1.5-1.8). The case fatality was 3.1%, also higher for children younger than 5 years (6.1% vs 2.1%; relative risk=2.9; 95% CI 2.1-4.1]). Among 583 patients regarded at increased risk of death who were treated with ciprofloxacin in isolation centres, case fatality was 0.9%. A 5-day ciprofloxacin regimen, targeted to the most severe cases of bloody diarrhoea, was highly effective. This is the first time a large outbreak caused by Sd1 has been reported in west Africa.

Conceptual framework of public health surveillance and action and its application in health sector reform.

BACKGROUND: Because both public health surveillance and action are crucial, the authors initiated meetings at regional and national levels to assess and reform surveillance and action systems. These meetings emphasized improved epidemic preparedness, epidemic response, and highlighted standardized assessment and reform. METHODS: To standardize assessments, the authors designed a conceptual framework for surveillance and action that categorized the framework into eight core and four support activities, measured with indicators. RESULTS: In application, country-level reformers measure both the presence and performance of the six core activities comprising public health surveillance (detection, registration, reporting, confirmation, analyses, and feedback) and acute (epidemic-type) and planned (management-type) responses composing the two core activities of public health action. Four support activities - communications, supervision, training, and resource provision - enable these eight core processes. National, multiple systems can then be concurrently assessed at each level for effectiveness, technical efficiency, and cost. CONCLUSIONS: This approach permits a cost analysis, highlights areas amenable to integration, and provides focused intervention. The final public health model becomes a district-focused, action-oriented integration of core and support activities with enhanced effectiveness, technical efficiency, and cost savings. This reform approach leads to sustained capacity development by an empowerment strategy defined as facilitated, process-oriented action steps transforming staff and the system.

Genome-wide analysis of novel splice variants induced by topoisomerase I poisoning shows preferential occurrence in genes encoding splicing factors.

RNA splicing is required to remove introns from pre-mRNA, and alternative splicing generates protein diversity. Topoisomerase I (Top1) has been shown to be coupled with splicing by regulating serine/arginine-rich splicing proteins. Prior studies on isolated genes also showed that Top1 poisoning by camptothecin (CPT), which traps Top1 cleavage complexes (Top1cc), can alter RNA splicing. Here, we tested the effect of Top1 inhibition on splicing at the genome-wide level in human colon carcinoma HCT116 and breast carcinoma MCF7 cells. The RNA of HCT116 cells treated with CPT for various times was analyzed with ExonHit Human Splice Array. Unlike other exon array platforms, the ExonHit arrays include junction probes that allow the detection of splice variants with high sensitivity and specificity. We report that CPT treatment preferentially affects the splicing of splicing-related factors, such as RBM8A, and generates transcripts coding for inactive proteins lacking key functional domains. The splicing alterations induced by CPT are not observed with cisplatin or vinblastine and are not simply due to reduced Top1 activity, as Top1 downregulation by short interfering RNA did not alter splicing like CPT treatment. Inhibition of RNA polymerase II (Pol II) hyperphosphorylation by 5,6-dichloro-1-ß-d-ribofuranosylbenzimidazole (DRB) blocked the splicing alteration induced by CPT, which suggests that the rapid Pol II hyperphosphorylation induced by CPT interferes with normal splicing. The preferential effect of CPT on genes encoding splicing factors may explain the abnormal splicing of a large number of genes in response to Top1cc.

NHS Direct versus general practice based triage for same day appointments in primary care: cluster randomised controlled trial.

OBJECTIVE: To assess the relative effects on consultation workload and costs of off-site triage by NHS Direct for patients requesting same day appointments compared with usual on-site nurse telephone triage in general practice. DESIGN: Cluster randomised controlled trial. SETTING: Three primary care sites in York, England. PARTICIPANTS: 4703 patients: 2452 with practice based triage, 2251 with NHS Direct triage. All consecutive patients making requests for same day appointments during study weeks were eligible for the trial. MAIN OUTCOME MEASURES: Type of consultation after request for same day appointment (telephone, appointment, or visit); time taken for consultation; service use during the month after same day contact; costs of same day, follow up, and emergency care. RESULTS: Patients in the NHS Direct group were less likely to have their call resolved by a nurse and were more likely to have an appointment with a general practitioner. Mean total time per patient in the NHS Direct group was 7.62 minutes longer than in the practice based group. Costs were greater in the NHS Direct group--2.88 pounds sterling (0.88 pounds sterling to 4.87 pounds sterling) per patient triaged--as a result of the difference between the groups in proportions of patients at each final point contact after triage. CONCLUSIONS: External management of requests for same day appointments by nurse telephone triage through NHS Direct is possible but comes at a higher cost than practice nurse delivered triage in primary care. If NHS Direct could achieve the same proportions of consultation types as practice based triage, costs would be comparable.