Integrating modes of policy analysis and strategic management practice : requisite elements and dilemmas

There is a need to bring methods to bear on public problems that are inclusive, analytic, and quick. This paper describes the efforts of three pairs of academics working from three different though complementary theoretical foundations and intervention backgrounds (i.e., ways of working) who set out together to meet this challenge. Each of the three pairs had conducted dozens of interventions that had been regarded as successful or very successful by the client groups in dealing with complex policy and strategic problems. One approach focused on leadership issues and stakeholders, another on negotiating competitive strategic intent with attention to stakeholder responses, and the third on analysis of feedback ramifications in developing policies. This paper describes the 10 year longitudinal research project designed to address the above challenge. The important outcomes are reported: the requisite elements of a general integrated approach and the enduring puzzles and tensions that arose from seeking to design a wide-ranging multi-method approach

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

Dynamics of a Quantum Phase Transition and Relaxation to a Steady State

We review recent theoretical work on two closely related issues: excitation of an isolated quantum condensed matter system driven adiabatically across a continuous quantum phase transition or a gapless phase, and apparent relaxation of an excited system after a sudden quench of a parameter in its Hamiltonian. Accordingly the review is divided into two parts. The first part revolves around a quantum version of the Kibble-Zurek mechanism including also phenomena that go beyond this simple paradigm. What they have in common is that excitation of a gapless many-body system scales with a power of the driving rate. The second part attempts a systematic presentation of recent results and conjectures on apparent relaxation of a pure state of an isolated quantum many-body system after its excitation by a sudden quench. This research is motivated in part by recent experimental developments in the physics of ultracold atoms with potential applications in the adiabatic quantum state preparation and quantum computation.Comment: 117 pages; review accepted in Advances in Physic

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Congenital cardiovascular defects in children with intestinal malrotation

Intestinal malrotation (IM) and cardiovascular defects (CCVD) are both common congenital defects. We investigated the prevalence and types of CCVD in a 25-year IM population, and its association with post-IM-operative morbidity and mortality. Data on the type of CCVD, other congenital defects, syndromes, associations, post-IM-operative morbidity and mortality were retrospectively reviewed from the records of IM patients born between 1980 and 2005. Data were analyzed on (significant) differences between CCVD subgroups, and risk factors for both morbidity and mortality were calculated. Seventy-seven of 284 IM patients (27.1%) were diagnosed with a major or minor CCVD (37 and 40 patients, respectively). Syndromes and associations were more frequently diagnosed in patients with major than with a minor CCVD (67.6 vs. 40%, respectively). Post-IM-operative complications, although frequently observed (61%), did not differ between patients with major and minor CCVD. Physical CCVD signs before IM surgery increased post-IM-operative morbidity significantly (OR 4.0, 95% CI 1.4–11.0). Fifteen patients died (19.5%), seven due to cardiovascular cause. Mortality risk was increased by intestinal ischemia and post-IM-operative complications and by major CCVD after correction for age at weight at the time of IM operation. Congenital cardiovascular defects in children with intestinal malrotation are common, with high morbidity and mortality rates after IM operation. Elective IM surgery in young patients with CCVD should be performed in a centre with adequate paediatric cardiac care. Benefits of laparoscopic intervention need further study

Application of Permutation Genetic Algorithm for Sequential Model Building–Model Validation Design of Experiments

YesThe work presented in this paper is motivated by a complex multivariate engineering problem associated with engine mapping experiments, which require efficient Design of Experiment (DoE) strategies to minimise expensive testing. The paper describes the development and evaluation of a Permutation Genetic Algorithm (PermGA) to support an exploration-based sequential DoE strategy for complex real-life engineering problems. A known PermGA was implemented to generate uniform OLH DoEs, and substantially extended to support generation of Model Building–Model Validation (MB-MV) sequences, by generating optimal infill sets of test points as OLH DoEs, that preserve good space filling and projection properties for the merged MB + MV test plan. The algorithm was further extended to address issues with non-orthogonal design spaces, which is a common problem in engineering applications. The effectiveness of the PermGA algorithm for the MB-MV OLH DoE sequence was evaluated through a theoretical benchmark problem based on the Six-Hump-Camel-Back (SHCB) function, as well as the Gasoline Direct Injection (GDI) engine steady state engine mapping problem that motivated this research. The case studies show that the algorithm is effective at delivering quasi-orthogonal space-filling DoEs with good properties even after several MB-MV iterations, while the improvement in model adequacy and accuracy can be monitored by the engineering analyst. The practical importance of this work, demonstrated through the engine case study, also is that significant reduction in the effort and cost of testing can be achieved.The research work presented in this paper was funded by the UK Technology Strategy Board (TSB) through the Carbon Reduction through Engine Optimization (CREO) project

Msh2 Blocks an Alternative Mechanism for Non-Homologous Tail Removal during Single-Strand Annealing in Saccharomyces cerevisiae

Chromosomal translocations are frequently observed in cells exposed to agents that cause DNA double-strand breaks (DSBs), such as ionizing radiation and chemotherapeutic drugs, and are often associated with tumors in mammals. Recently, translocation formation in the budding yeast, Saccharomyces cerevisiae, has been found to occur at high frequencies following the creation of multiple DSBs adjacent to repetitive sequences on non-homologous chromosomes. The genetic control of translocation formation and the chromosome complements of the clones that contain translocations suggest that translocation formation occurs by single-strand annealing (SSA). Among the factors important for translocation formation by SSA is the central mismatch repair (MMR) and homologous recombination (HR) factor, Msh2. Here we describe the effects of several msh2 missense mutations on translocation formation that suggest that Msh2 has separable functions in stabilizing annealed single strands, and removing non-homologous sequences from their ends. Additionally, interactions between the msh2 alleles and a null allele of RAD1, which encodes a subunit of a nuclease critical for the removal of non-homologous tails suggest that Msh2 blocks an alternative mechanism for removing these sequences. These results suggest that Msh2 plays multiple roles in the formation of chromosomal translocations following acute levels of DNA damage

Enhanced Discrimination of Malignant from Benign Pancreatic Disease by Measuring the CA 19-9 Antigen on Specific Protein Carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease