What to do about poor clinical performance in clinical trials

The performance of individual clinicians is being monitored as never before. Su Mason and colleagues discuss the implications of this for clinical trials and recommend what should happen if during a trial the performance of one clinician or one centre is identified as being particularly poor. Tom Treasure, a surgeon, wants the monitoring to be done fairly and to take account of the complexities of clinical practice; and Heather Goodare, a patient, wants to be told when things go wrong. The Department of Health in England has issued guidelines for research governance stating that healthcare organisations remain responsible for the quality of all aspects of patients' care whether or not some aspects of the care are part of a research study.1 We discuss how this obligation can be met in multicentre trials, given that data on the performance of clinicians are held by the trial management team, not by the host organisation

A statistical multiresolution approach for face recognition using structural hidden Markov models

This paper introduces a novel methodology that combines the multiresolution feature of the discrete wavelet transform (DWT) with the local interactions of the facial structures expressed through the structural hidden Markov model (SHMM). A range of wavelet filters such as Haar, biorthogonal 9/7, and Coiflet, as well as Gabor, have been implemented in order to search for the best performance. SHMMs perform a thorough probabilistic analysis of any sequential pattern by revealing both its inner and outer structures simultaneously. Unlike traditional HMMs, the SHMMs do not perform the state conditional independence of the visible observation sequence assumption. This is achieved via the concept of local structures introduced by the SHMMs. Therefore, the long-range dependency problem inherent to traditional HMMs has been drastically reduced. SHMMs have not previously been applied to the problem of face identification. The results reported in this application have shown that SHMM outperforms the traditional hidden Markov model with a 73% increase in accuracy

Cost effectiveness of a community based exercise programme in over 65 year olds: cluster randomised trial

OBJECTIVE: To assess the cost effectiveness of a community based exercise programme as a population wide public health intervention for older adults. DESIGN: Pragmatic, cluster randomised community intervention trial. Setting: 12 general practices in Sheffield; four randomly selected as intervention populations, and eight as control populations. PARTICIPANTS: All those aged 65 and over in the least active four fifths of the population responding to a baseline survey. There were 2283 eligible participants from intervention practices and 4137 from control practices. INTERVENTION: Eligible subjects were invited to free locally held exercise classes, made available for two years. MAIN OUTCOME MEASURES: All cause and exercise related cause specific mortality and hospital service use at two years, and health status assessed at baseline, one, and two years using the SF-36. A cost utility analysis was also undertaken. RESULTS: Twenty six per cent of the eligible intervention practice population attended one or more exercise sessions. There were no significant differences in mortality rates, survival times, or admissions. After adjusting for baseline characteristics, patients in intervention practices had a lower decline in health status, although this reached significance only for the energy dimension and two composite scores (p,0.05). The incremental average QALY gain of 0.011 per person in the intervention population resulted in an incremental cost per QALY ratio of J17 174 (95% CI =J8300 to J87 120). CONCLUSIONS: Despite a low level of adherence to the exercise programme, there were significant gains in health related quality of life. The programme was more cost effective than many existing medical interventions, and would be practical for primary care commissioning agencies to implement

Monitoring osteoarthritis: a cross-sectional survey in general practice

<b>Background</b> Despite being a highly prevalent chronic condition managed predominantly in primary care and unlike other chronic conditions, osteoarthritis (OA) care is delivered on an ad hoc basis rather than through routine structured review. Evidence suggests current levels of OA care are suboptimal, but little is known about what general practitioners' (GPs) consider important in OA care, and, thus, the scope to improve inconsistency or poor practice is, at present, limited.<p></p> <b>Objectives</b> We investigated GPs' views on and practice of monitoring OA. <p></p> <b>Methods</b> This was a cross-sectional postal survey of 2500 practicing UK GPs randomly selected from the Binley's database. Respondents were asked if monitoring OA patients was important and how monitoring should be undertaken.<p></p> <b>Results</b> Responses were received from 768 GPs of whom 70.8% were male and 89.5% were principals within their practices. Despite 55.4% (n = 405) indicating monitoring patients with OA was important and 78.3% (n = 596) considering GPs the appropriate professionals to monitor OA, only 15.2% (n = 114) did so routinely, and 45% (n = 337) did not monitor any OA patients at all. In total, 61.4% (n = 463) reported that patients should self-monitor. Respondents favored monitoring physical function, pain, and analgesia use over monitoring measures of BMI, self management plans, and exercise advice.<p></p> <b>Conclusions</b> The majority of respondents felt that monitoring OA was important, but this was not reflected in their reported current practice. Much of what they favored for monitoring was in line with published guidance, suggesting provision of suboptimal care does not result from lack of knowledge and interventions to improve OA care must address barriers to GPs engaging in optimal care provision

The luminosity function of TDEs from fallback-powered emission: implications for the black hole mass function

Tidal disruption events (TDEs), in which a star is destroyed by the gravitational field of a supermassive black hole (SMBH), are being observed at a high rate owing to the advanced state of survey science. One of the properties of TDEs that is measured with increasing statistical reliability is the TDE luminosity function, $d\dot{N}_{\rm TDE}/dL$, which is the TDE rate per luminosity (i.e., how many TDEs are within a given luminosity range). Here we show that if the luminous emission from a TDE is directly coupled to the rate of return of tidally destroyed debris to the SMBH, then the TDE luminosity function is in good agreement with observations and scales as $\propto L^{-2.5}$ for high luminosities, provided that the SMBH mass function $dN_{\bullet}/dM_{\bullet}$ -- the number of SMBHs ($N_{\bullet}$) per SMBH mass ($M_{\bullet}$) -- is approximately flat in the mass range over which we observe TDEs. We also show that there is a cutoff in the luminosity function at low luminosities that is a result of direct captures, and this cutoff has been tentatively observed. If $dN_{\bullet}/dM_{\bullet}$ is flat, which is in agreement with some observational campaigns, these results suggest that the fallback rate feeds the accretion rate in TDEs. Contrarily, if $dN_{\bullet}/d\log M_{\bullet}$ is flat, which has been found theoretically and is suggested by other observational investigations, then the emission from TDEs is likely powered by another mechanism. Future observations and more TDE statistics, provided by the Rubin Observatory/LSST, will provide additional evidence as to the reality of this tension.Comment: 7 pages, 1 figure, ApJL accepte

A Hydrogen-Poor Superluminous Supernova with Enhanced Iron-Group Absorption: A New Link Between SLSNe and Broad-Lined Type Ic SNe

We present optical observations of the Type I superluminous supernova (SLSN-I) SN2017dwh at $z\!\approx\!0.13$, which reached $M_{i}\!\approx\!-21$ mag at peak. Spectra taken a few days after peak show an unusual and strong absorption line centered near 3200\AA\ that we identify with Co II, suggesting a high fraction of synthesized $^{56}$Ni in the ejecta. By $\sim\!1$ month after peak, SN2017dwh became much redder than other SLSNe-I, instead strongly resembling broad-lined Type Ic supernovae (Ic-BL SNe) with clear suppression of the flux redward of $\sim\!5000$ \AA, providing further evidence for a large mass of Fe-group elements. Late-time upper limits indicate a $^{56}$Ni mass of $\lesssim 0.6$ M$_\odot$, leaving open the possibility that SN2017dwh produced a $^{56}$Ni mass comparable to SN1998bw ($\approx\!0.4$ M$_\odot$). Fitting the light curve with a combined magnetar and $^{56}$Ni model using ${\tt MOSFiT}$, we find that the light curve can easily accommodate such masses without affecting the inferred magnetar parameters. We also find that SN2017dwh occurred in the least-luminous detected host galaxy to date for a SLSN-I, with $M_{B} = -13.5$ mag and an implied metallicity of $Z\!\sim\!0.08$ $Z_\odot$. The spectral properties of SN2017dwh provide new evidence linking SLSNe-I with Type Ic-BL SNe, and in particular the high Fe-group abundance may be due to enhanced $^{56}$Ni production or mixing due to asphericity. Finally, we find that SN2017dwh represents the most extreme end of a correlation between continuum shape and Co II absorption strength in the near-peak spectra of SLSNe-I, indicating that Fe-group abundance likely accounts for some of the variation in their spectral shapes.Comment: 16 pages, 7 figures, Submitted to Ap

Outbreak report of investigation and control of an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in neonates and mothers

Background In January 2011, there was an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in a neonatal unit (NNU). We describe the investigation and control of an outbreak of PVL-MSSA infection in neonates. Setting: Neonatal unit in West London. Methods We performed descriptive and analytical (case-control study) epidemiological investigations. Microbiological investigations including screening of MSSA isolates by PCR for the presence of the luk-PV, mecA and mecC genes and comparison of isolate with Pulsed field gel electrophoresis (PFGE). Control measures were also introduced. Results Sixteen babies were infected/colonised with the outbreak strain. Of these, one baby developed blood stream infection, 12 developed skin pustules and four babies were colonised. Four mothers developed breast abscesses. Eighty-seven babies in the unit were screened and 16 were found to have same PVL-MSSA strain (spa type t005, belonging to MLST clonal complex 22). Multivariate analysis showed gestational age was significantly lower in cases compared to controls (mean gestational age: 31.7 weeks v 35.6 weeks; P = 0.006). Length of stay was significantly greater for cases, with a median of 25 days, compared to only 6 days for controls (P = 0.01). Most (88%) cases were born through caesarean section, compared to less than half of controls. (P = 0.002). No healthcare worker carriers and environmental source was identified. The outbreak was controlled by stopping new admissions to unit and reinforcing infection control precautions. The outbreak lasted for seven weeks. No further cases were reported in the following year. Conclusions Infection control teams have to be vigilant for rising prevalence of particular S. aureus clones in their local community as they may cause outbreaks in vulnerable populations in healthcare settings such as NNUs

Hidden area and mechanical nonlinearities in freestanding graphene

We investigated the effect of out-of-plane crumpling on the mechanical response of graphene membranes. In our experiments, stress was applied to graphene membranes using pressurized gas while the strain state was monitored through two complementary techniques: interferometric profilometry and Raman spectroscopy. By comparing the data obtained through these two techniques, we determined the geometric hidden area which quantifies the crumpling strength. While the devices with hidden area $\sim0~\%$ obeyed linear mechanics with biaxial stiffness $428\pm10$ N/m, specimens with hidden area in the range $0.5-1.0~\%$ were found to obey an anomalous Hooke's law with an exponent $\sim0.1$

PS16dtm: A Tidal Disruption Event in a Narrow-line Seyfert 1 Galaxy

[Abridged] We present observations of PS16dtm, a luminous transient that occurred at the nucleus of a known Narrow-line Seyfert 1 galaxy hosting a 10$^6$ M$_\odot$ black hole. The transient was previously claimed to be a Type IIn SLSN due to its luminosity and hydrogen emission lines. The light curve shows that PS16dtm brightened by about two magnitudes in ~50 days relative to the archival host brightness and then exhibited a plateau phase for about 100 days followed by the onset of fading in the UV. During the plateau PS16dtm showed no color evolution, maintained a blackbody temperature of 1.7 x 10$^4$ K, and radiated at approximately $L_{Edd}$ of the SMBH. The spectra exhibit multi-component hydrogen emission lines and strong FeII emission, show little evolution with time, and closely resemble the spectra of NLS1s while being distinct from those of Type IIn SNe. Moreover, PS16dtm is undetected in the X-rays to a limit an order of magnitude below an archival X-ray detection of its host galaxy. These observations strongly link PS16dtm to activity associated with the SMBH and are difficult to reconcile with a SN origin or any known form of AGN variability, and therefore we argue that it is a TDE in which the accretion of the stellar debris powers the rise in the continuum and excitation of the pre-existing broad line region, while providing material that obscures the X-ray emitting region of the pre-existing AGN accretion disk. A detailed TDE model fit to the light curve indicates that PS16dtm will remain bright for several years; we further predict that the X-ray emission will reappear on a similar timescale as the accretion rate declines. Finally, we place PS16dtm in the context of other TDEs and find that TDEs in AGN galaxies are an order of magnitude more efficient and reach Eddington luminosities, likely due to interaction of the stellar debris with the pre-existing accretion disk.Comment: 19 pages, 17 figures, Submitted to Ap

An ultraviolet excess in the superluminous supernova Gaia16apd reveals a powerful central engine

Since the discovery of superluminous supernovae (SLSNe) in the last decade, it has been known that these events exhibit bluer spectral energy distributions than other supernova subtypes, with significant output in the ultraviolet. However, the event Gaia16apd seems to outshine even the other SLSNe at rest-frame wavelengths below $\sim 3000$ \AA. Yan et al (2016) have recently presented HST UV spectra and attributed the UV flux to low metallicity and hence reduced line blanketing. Here we present UV and optical light curves over a longer baseline in time, revealing a rapid decline at UV wavelengths despite a typical optical evolution. Combining the published UV spectra with our own optical data, we demonstrate that Gaia16apd has a much hotter continuum than virtually any SLSN at maximum light, but it cools rapidly thereafter and is indistinguishable from the others by $\sim 10$-15 days after peak. Comparing the equivalent widths of UV absorption lines with those of other events, we show that the excess UV continuum is a result of a more powerful central power source, rather than a lack of UV absorption relative to other SLSNe or an additional component from interaction with the surrounding medium. These findings strongly support the central-engine hypothesis for hydrogen-poor SLSNe. An explosion ejecting $M_{\rm ej} = 4 (0.2/\kappa)$ M$_\odot$, where $\kappa$ is the opacity in cm$^2$g$^{-1}$, and forming a magnetar with spin period $P=2$ ms, and $B=2\times10^{14}$ G (lower than other SLSNe with comparable rise-times) can consistently explain the light curve evolution and high temperature at peak. The host metallicity, $Z=0.18$ Z$_\odot$, is comparable to other SLSNe.Comment: Updated to match accepted version (ApJL