The challenges of change:Exploring the dynamics of police reform in Scotland

Despite a long tradition of pessimism regarding the scope for meaningful change in police practices, recent structural reforms to police organizations in several European countries suggest that significant change in policing is possible. Drawing on recent research into the establishment and consequences of a national police force in Scotland, this article uses instrumental, cultural and myth perspectives taken from organization theory to examine how change happened and with what effects. It highlights how police reform involves a complex interplay between the strategic aims of government, the cultural norms of police organizations and the importance of alignment with wider views about the nature of the public sector. The article concludes by identifying a set of wider lessons from the experience of organizational change in policing

Motility of an autonomous protein-based artificial motor that operates via a burnt-bridge principle

Inspired by biology, great progress has been made in creating artificial molecular motors. However, the dream of harnessing proteins – the building blocks selected by nature – to design autonomous motors has so far remained elusive. Here we report the synthesis and characterization of the Lawnmower, an autonomous, protein-based artificial molecular motor comprised of a spherical hub decorated with proteases. Its “burnt-bridge” motion is directed by cleavage of a peptide lawn, promoting motion towards unvisited substrate. We find that Lawnmowers exhibit directional motion with average speeds of up to 80 nm/s, comparable to biological motors. By selectively patterning the peptide lawn on microfabricated tracks, we furthermore show that the Lawnmower is capable of track-guided motion. Our work opens an avenue towards nanotechnology applications of artificial protein motors

Globular Cluster Distance Determinations

The present status of the distance scale to Galactic globular clusters is reviewed. Six distance determination techniques which are deemed to be most reliable are discussed in depth. These different techniques are used to calibrate the absolute magnitude of the RR Lyrae stars. The various calibrations fall into three groups. Main sequence fitting using Hipparcos parallaxes, theoretical HB models and the RR Lyrae in the LMC all favor a bright calibration, implying a `long' globular cluster distance scale. White dwarf fitting and the astrometric distances yield a somewhat fainter RR Lyrae calibration, while the statistical parallax solution yields faint RR Lyrae stars implying a `short' distance scale to globular clusters. Various secondary distance indicators discussed all favor the long distance scale. The `long' and `short' distance scales differ by (0.31+/-0.16) mag. Averaging together all of the different distance determinations yields Mv(RR) = (0.23+/-0.04)([Fe/H] + 1.6) + (0.56+/-0.12) mag.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in pres

Breast cancer research and the European Union Clinical Trials Directive

Running clinical trials in the commercial sector has always been associated with a certain amount of bureaucracy due to the stringent requirements needed to bring a new drug onto the market. Noncommercial trials have largely been performed outside these requirements. New legislation brought about as a result of the implementation of the European Union Clinical Trials Directive will change this two-tiered approach by harmonizing regulations in all member states. Those who run noncommercial clinical trials will have to find cost-effective ways of dealing with this legislation if such work is to continue in Europe

Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes and time-dependencies, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival (that would be observed in the absence of switching) at the end of the simulated trial follow-up. We found that RPSFTM and TSE analyses which incorporated re-censoring usually produced negative bias (i.e. under-estimating control group restricted mean survival and therefore over-estimating the treatment effect). RPSFTM and TSE analyses that did not incorporate re-censoring consistently produced positive bias (i.e. under-estimating the treatment effect) which was often smaller in magnitude than the bias associated with the re-censored analyses. We believe that analyses should be conducted with and without re-censoring, as this may provide decision makers with useful information on where the true treatment effect is likely to lie. Analyses that incorporate re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects on long-term survival

First Report of Wenzhou sobemo-like virus 4 in Aedes albopictus (Diptera: Culicidae) in Latin America

Insect-specific viruses (ISVs) are viruses that replicate exclusively in arthropod cells. Many ISVs have been studied in mosquitoes as many of them act as vectors for human etiological agents, such as arboviruses. Aedes (Stegomyia) albopictus is an important potential vector of several arboviruses in Brazil, such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV). The development of next-generation sequencing metagenomics has enabled the discovery and characterization of new ISVs. Ae. albopictus eggs were collected using oviposition traps placed in two urban parks in the city of São Paulo, Brazil. The Aedes albopictus females were divided into pools and the genetic material was extracted and processed for sequencing by metagenomics. Complete genomes of ISV Wenzhou sobemo-like virus 4 (WSLV4) were obtained in three of the four pools tested. This is the first detection of ISV WSLV4 in Ae. albopictus females in Latin America. Further studies on ISVs in Ae. albopictus are needed to better understand the role of this species in the dynamics of arbovirus transmission in the Americas

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission

Local governance in the new Police Scotland:Renegotiating power, recognition and responsiveness

A marked, but by no means universal, trend in Europe over the last decade or so has been the centralization or amalgamation of regional police organizations into larger or single units. Scotland is a case in point, its eight regional services becoming one Police Scotland in April 2013. Although the reform process was relatively consensual, the new organization has been the subject of numerous controversies, some of which reflect an actual or perceived loss of the local in Scottish policing. Drawing on a qualitative study of the emerging local governance arrangements, we explore the negotiated character of large-scale organizational reform, demonstrating that it is best understood as a process not an event. We also argue that appeals to localism are not mere expressions of sentiment and resistance to change. They reflect the particular historical development of policing and public service delivery in Scotland at the level of municipal government, but also strong convictions that policing should be subject to democratic deliberation and should recognize and be responsive to those subject to it – what we argue here are necessary functions of police governance in general

Assessing methods for dealing with treatment switching in clinical trials: A follow-up simulation study

When patients randomised to the control group of a randomised controlled trial are allowed to switch onto the experimental treatment, intention-to-treat analyses of the treatment effect are confounded because the separation of randomised groups is lost. Previous research has investigated statistical methods that aim to estimate the treatment effect that would have been observed had this treatment switching not occurred and has demonstrated their performance in a limited set of scenarios. Here, we investigate these methods in a new range of realistic scenarios, allowing conclusions to be made based upon a broader evidence base. We simulated randomised controlled trials incorporating prognosis-related treatment switching and investigated the impact of sample size, reduced switching proportions, disease severity, and alternative data-generating models on the performance of adjustment methods, assessed through a comparison of bias, mean squared error, and coverage, related to the estimation of true restricted mean survival in the absence of switching in the control group. Rank preserving structural failure time models, inverse probability of censoring weights, and two-stage methods consistently produced less bias than the intentionto-treat analysis. The switching proportion was confirmed to be a key determinant of bias: sample size and censoring proportion were relatively less important. It is critical to determine the size of the treatment effect in terms of an acceleration factor (rather than a hazard ratio) to provide information on the likely bias associated with rank-preserving structural failure time model adjustments. In general, inverse probability of censoring weight methods are more volatile than other adjustment methods