THE FEDERAL ROLE IN SMALL AREA PLANNING

Public Economics,

Managing risk in cancer presentation, detection and referral: a qualitative study of primary care staff views

Objectives In the UK, there have been a number of national initiatives to promote earlier detection and prompt referral of patients presenting to primary care with signs and symptoms of cancer. The aim of the study was to explore the experiences of a range of primary care staff in promoting earlier presentation, detection and referral of patients with symptoms suggestive of cancer. Setting Six primary care practices in northwest England. Participants: 39 primary care staff from a variety of disciplines took part in five group and four individual interviews. Results The global theme to emerge from the interviews was ‘managing risk’, which had three underpinning organising themes: ‘complexity’, relating to uncertainty of cancer diagnoses, service fragmentation and plethora of guidelines; ‘continuity’, relating to relationships between practice staff and their patients and between primary and secondary care; ‘conflict’ relating to policy drivers and staff role boundaries. A key concern of staff was that policymakers and those implementing cancer initiatives did not fully understand how risk was managed within primary care. Conclusions Primary care staff expressed a range of views and opinions on the benefits of cancer initiatives. National initiatives did not appear to wholly resolve issues in managing risk for all practitioners. Staff were concerned about the number of guidelines and priorities they were expected to implement. These issues need to be considered by policymakers when developing and implementing new initiatives

Unusual behaviour of Dickey-Fuller tests in the presence of trend mis-specification

This paper analyses the properties of Dickey-Fuller (1979) (DF) unit root tests in the presence of trend mis-specification. It is shown that while the performance of the DF coefficient test is as expected, the DF test in its t-ratio form exhibits unusual behaviour. In particular it is found that the power of the test increases as the autoregressive parameter approaches 1. Interestingly, this increased power is not accompanied by oversizing.DF test

Baculovirus-Mediated Expression of Human 65 kDa and 67 kDa Glutamic Acid Decarboxylases in SF9 Insect Cells and Their Relevance in Diagnosis of Insulin-Dependent Diabetes Mellitus

cDNAs coding for the full-length human 65 and 67 kDa glutamic acid decarboxylases (GAD65 and GAD67) were amplified from pancreas and hippocampus cDNA libraries by polymerase chain reaction, respectively. Both cDNAs were inserted into a baculovirus vector which mediated highly efficient expression of the human GAD65 and GAD67 with histidine-hexapeptides as affinity ligands at their C-termini in Spodoptera frugiperda (Sf9) cells. The recombinant GAD proteins were purified to homogeneity by affinity chromatography using a metal-chelating matrix. The infected Sf9 insect cells expressed the recombinant human GAD65 and GAD67 with natural-like conformations, as confirmed by measurement of their enzyme activities as well as their fully restored autoantigenicities. Immunoprecipitation of metabolically labeled infected Sf9 cells demonstrated the autoantigenic potential of the recombinant GAD proteins. The practicability of using recombinant GAD65 and GAD67 derived from the baculovirus expression system for the development of an immunoassay for the diagnosis of insulin-dependent diabetes mellitus is discussed

Measurement of Plasmodium falciparum transmission intensity using serological cohort data from Indonesian schoolchildren.

BACKGROUND: As malaria transmission intensity approaches zero, measuring it becomes progressively more difficult and inefficient because parasite-positive individuals are hard to detect. This situation may arise shortly before achieving local elimination, or during surveillance post-elimination to prevent reintroduction. Antibody responses against the parasite last longer than the infections themselves. This "footprint" of infection may thus be used for assessing transmission intensity. A statistical approach is presented for measuring the seroconversion rate (SCR), a correlate of the force of infection, from individual-level longitudinal data on antibody titres in an area of low Plasmodium falciparum transmission. METHODS: Blood samples were collected from 160 Indonesian schoolchildren every month for six months. Titres of antibodies against AMA-1 and MSP-1(19) antigens of P. falciparum were measured using ELISA. The distribution of antibody titres among seronegative and -positive individuals, respectively, was estimated by comparing the titres from the study data (a mixture of both seropositive and -negative individuals) with titres from a (unexposed) negative control group of Indonesian individuals. Two Markov-Chain models for the transition of individuals between serological states were fitted to individual anti-PfAMA-1 or anti-PfMSP-1 titre time series using Bayesian Markov-Chain-Monte-Carlo (MCMC). This yielded estimates of SCR as well as of the duration of seropositivity. RESULTS: A posterior median SCR of 0.02 (Pf AMA-1) and 0.09 (PfMSP-1) person(-1) year(-1) was estimated, with credible intervals ranging from 1E-4 to 0.2 person(-1) year(-1). This level of transmission intensity is at the lower range of what can reliably be measured with the present study size. A Bayesian test for seroconversion of an individual between two observations is presented and used to identify the subjects who have most likely experienced an infection. Furthermore, the theoretical limits of measuring transmission intensity, and how these depend on duration and size of a study as well as on transmission intensity itself, is illustrated. CONCLUSIONS: This analysis shows that it is possible to measure SCR's from individual-level longitudinal data on antibody titres. In addition, individual seroconversion events can be identified, which can be useful in assessing interruption of transmission. Analyses of further serological datasets using the present method are required to improve and validate it. This includes measurement of the duration of antibody responses, how it depends on host age or cumulative exposure, or on the particular antigen used

Purkinje cell injury, structural plasticity and fusion in patients with Friedreich's ataxia

Purkinje cell pathology is a common finding in a range of inherited and acquired cerebellar disorders, with the degree of Purkinje cell injury dependent on the underlying aetiology. Purkinje cells have an unparalleled resistance to insult and display unique regenerative capabilities within the central nervous system. Their response to cell injury is not typical of most neurons and likely represents both degenerative, compensatory and regenerative mechanisms. Here we present a pathological study showing novel and fundamental insights into Purkinje cell injury, remodelling and repair in Friedreich’s ataxia; the most common inherited ataxia. Analysing post-mortem cerebellum tissue from patients who had Friedreich's ataxia, we provide evidence of significant injury to the Purkinje cell axonal compartment with relative preservation of both the perikaryon and its extensive dendritic arborisation. Axonal remodelling of Purkinje cells was clearly elevated in the disease. For the first time in a genetic condition, we have also shown a disease-related increase in the frequency of Purkinje cell fusion and heterokaryon formation in Friedreich's ataxia cases; with evidence that underlying levels of cerebellar inflammation influence heterokaryon formation. Our results together further demonstrate the Purkinje cell’s unique plasticity and regenerative potential. Elucidating the biological mechanisms behind these phenomena could have significant clinical implications for manipulating neuronal repair in response to neurological injury

Theories for TC0 and Other Small Complexity Classes

We present a general method for introducing finitely axiomatizable "minimal" two-sorted theories for various subclasses of P (problems solvable in polynomial time). The two sorts are natural numbers and finite sets of natural numbers. The latter are essentially the finite binary strings, which provide a natural domain for defining the functions and sets in small complexity classes. We concentrate on the complexity class TC^0, whose problems are defined by uniform polynomial-size families of bounded-depth Boolean circuits with majority gates. We present an elegant theory VTC^0 in which the provably-total functions are those associated with TC^0, and then prove that VTC^0 is "isomorphic" to a different-looking single-sorted theory introduced by Johannsen and Pollet. The most technical part of the isomorphism proof is defining binary number multiplication in terms a bit-counting function, and showing how to formalize the proofs of its algebraic properties.Comment: 40 pages, Logical Methods in Computer Scienc

ProtoEXIST: Advanced Prototype CZT Coded Aperture Telescopes for EXIST

{\it ProtoEXIST1} is a pathfinder for the {\it EXIST-HET}, a coded aperture hard X-ray telescope with a 4.5 m$^2$ CZT detector plane a 90$\times$70 degree field of view to be flown as the primary instrument on the {\it EXIST} mission and is intended to monitor the full sky every 3 h in an effort to locate GRBs and other high energy transients. {\it ProtoEXIST1} consists of a 256 cm$^2$ tiled CZT detector plane containing 4096 pixels composed of an 8$\times$8 array of individual 1.95 cm $\times$ 1.95 cm $\times$ 0.5 cm CZT detector modules each with a 8 $\times$ 8 pixilated anode configured as a coded aperture telescope with a fully coded $10^\circ\times10^\circ$ field of view employing passive side shielding and an active CsI anti-coincidence rear shield, recently completed its maiden flight out of Ft. Sumner, NM on the 9th of October 2009. During the duration of its 6 hour flight on-board calibration of the detector plane was carried out utilizing a single tagged 198.8 nCi Am-241 source along with the simultaneous measurement of the background spectrum and an observation of Cygnus X-1. Here we recount the events of the flight and report on the detector performance in a near space environment. We also briefly discuss {\it ProtoEXIST2}: the next stage of detector development which employs the {\it NuSTAR} ASIC enabling finer (32$\times$32) anode pixilation. When completed {\it ProtoEXIST2} will consist of a 256 cm$^2$ tiled array and be flown simultaneously with the ProtoEXIST1 telescope

Do people who consciously attend to their movements have more self-reported knee pain? An exploratory cross-sectional study

Objectives: This study explored the relationship between propensity for conscious control of movement (assessed by the Movement-Specific Reinvestment Scale) and self-reported knee pain. Design: Cross-sectional study. Setting: General population. Subjects: Adults aged 18 to 55 years of age. Measures: Participants completed the movement-specific reinvestment scale and a self-report questionnaire on knee pain at the same time on one occasion. Results: Data was collected on 101 adults of whom 34 (33.7%) self-reported knee pain. Mean scores on the conscious motor processing subscale of the movement-specific reinvestment scale, but not the movement self-consciousness subscale, were significantly higher for participants who reported knee pain within the previous year compared with those who did not (mean difference 3.03; t-test 2.66, df = 97, P = 0.009; 95% confidence interval (CI) 0.77 to 5.30). The association between self-reported knee pain and propensity for conscious motor processing was still observed, even after controlling for movement self-consciousness subscale scores, age, gender and body mass index (adjusted odds ratio 1.16, 95% CI 1.04 to 1.30)