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Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Radiocarbon dating and Bayesian chronological modelling have provided precise new dating for the henge monument of Mount Pleasant in Dorset, excavated in 1970–1. A total of 59 radiocarbon dates are now available for the site and modelling of these has provided a revised sequence for the henge enclosure and its various constituent parts: the timber palisaded enclosure, the Conquer Barrow, and the ditch surrounding Site IV, a concentric timber and stone monument. This suggests that the henge was probably built in the 26th century cal bc, shortly followed by the timber palisade and Site IV ditch. These major construction events took place in the late Neolithic over a relatively short timespan, probably lasting 35–125 years. The principal results are discussed for each element of the site, including comparison with similar monument types elsewhere in Britain and Ireland, and wider implications for late Neolithic connections and later activity at the site associated with Beaker pottery are explored.
We undertook a strengths, weaknesses, opportunities, and threats (SWOT) analysis of Northern Hemisphere tree-ring datasets included in IntCal20 in order to evaluate their strategic fit with the demands of archaeological users. Case studies on wiggle-matching single tree rings from timbers in historic buildings and Bayesian modeling of series of results on archaeological samples from Neolithic long barrows in central-southern England exemplify the archaeological implications that arise when using IntCal20. The SWOT analysis provides an opportunity to think strategically about future radiocarbon (14C) calibration so as to maximize the utility of 14C dating in archaeology and safeguard its reputation in the discipline.
Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.
Since 1993 Historic England (and its predecessor English Heritage) has commissioned 9074 radiocarbon (14C) measurements on archaeological samples. Over 80% of these have been interpreted within formal Bayesian statistical models. The multiple strands of reinforcing evidence incorporated in these models provide precise chronologies that make stringent demands on the accuracy of the 14C results included in the analysis. Inter-laboratory replication is consequently a routine part of model construction and validation. We report an analysis of replicate measurements on 1089 archaeological samples. It is clear that laboratory reproducibility accounts for only part of the observed variation. The type of material dated is also critical to the reproducibility of measurements, with some sample types proving particularly problematic.
In late summer, sometime between cal a.d. 340–405, a hoard of tightly packed, stacked copper-alloy vessels was deposited in the Vale of Pewsey, Wiltshire. The corrosion of the vessels allowed for the preservation of delicate plant macrofossils and pollen. Analysis of this material has provided insights into the date, season and context of this act of structured deposition. A second hoard of similar vessels was deposited in the fourth or fifth century only a few miles away at Wilcot. The hoards and their deposition relate to Romano-British lifeways, at a time when the region was on the cusp of a dramatic period of change. The distribution of late Roman coins and belt fittings offers further insights into the social and economic character of Wiltshire at their times of deposition.
England's first Tudor monarchs were formally devoted to the cult of St Thomas of Canterbury. In popular memory, however, Thomas was a champion of law and custom, an opponent of untrammelled royal power, and – especially among the clergy – a martyr for ecclesiastical ‘liberties’. This suggests that the pre-Reformation Church was considerably less ‘monarchical’ than is sometimes supposed. In the 1530s Thomas became a powerful symbol of resistance to Henry VIII's royal supremacy. However, the fact that he could be portrayed as a patron of the clergy's sectional interests helps to explain how opposition was weakened and divided.
New radiocarbon dating and chronological modelling have refined understanding of the character and circumstances of flint mining at Grime’s Graves through time. The deepest, most complex galleried shafts were worked probably from the third quarter of the 27th century cal bc and are amongst the earliest on the site. Their use ended in the decades around 2400 cal bc, although the use of simple, shallow pits in the west of the site continued for perhaps another three centuries. The final use of galleried shafts coincides with the first evidence of Beaker pottery and copper metallurgy in Britain. After a gap of around half a millennium, flint mining at Grime’s Graves briefly resumed, probably from the middle of the 16th century cal bc to the middle of the 15th. These ‘primitive’ pits, as they were termed in the inter-war period, were worked using bone tools that can be paralleled in Early Bronze Age copper mines. Finally, the scale and intensity of Middle Bronze Age middening on the site is revealed, as it occurred over a period of probably no more than a few decades in the 14th century cal bc. The possibility of connections between metalworking at Grime’s Graves at this time and contemporary deposition of bronzes in the nearby Fens is discussed.
We derive azimuthally-averaged surface-brightness profiles of 16 AGB stars in the far-IR and sub-mm with the aim of studying the resolved historic mass loss in the extended circumstellar envelope. The PSF-subtracted extended component fluxes were found to be ∼40% of the total source flux. By fitting SEDs at each radial point we derive the dust temperature, column density and spectral index of emissivity via Bayesian inference. The measured dust-to-gas ratios were somewhat consistent with canonical values however with a large scatter.
All hospital staff were very respectful of our wishes and explained everything well that they needed to do. We were given plenty of time and privacy with all our family after the baby died.
I was sat in the back of the police car and no-one spoke to me, I always remember the silence, it was awful, the silence was so bad.
When a child dies suddenly and unexpectedly, we, as professionals, have a wide range of duties and obligations that must be fulfilled. Statutory requirements may place constraints on what we can do, when we need to do it, and how we can go about it. At the heart of it all, however, there remains a bereaved family, for whom the worst thing imaginable has just happened. As one bereaved mother put it: “Words may hurt me or make me angry, but I have lost my child, so don't flatter yourself — nothing that you say will actually make the situation worse”.
Nevertheless, as the quotes at the start of this chapter highlight, parents’ experiences following the death of their child vary enormously, and the way we respond to them can make a considerable difference. The way we respond can make a difference also to the outcome of an investigation. Identifying an unusual medical cause of death, or uncovering the circumstances of a tragic accident or a case of intentional filicide is more likely with a thorough, systematic investigation, conducted with sensitivity and respect, than with one carried out carelessly or in a haphazard or aggressive manner.
In most jurisdictions, the sudden unexpected death of an infant or child requires the case to be referred to a coroner, medical examiner, or procurator fiscal. In England, for example, a coroner is obliged to conduct an investigation into violent or unnatural deaths, deaths where the cause is unknown, and deaths which occur in custody or otherwise in state detention (1). Coroner's officers, or police officers acting on behalf of the coroner, will need to carry out an investigation into the causes and circumstances of the death.
The lower Mississippian Ballagan Formation of northern Britain is one of only two successions worldwide to yield the earliest known tetrapods with terrestrial capability following the end-Devonian mass extinction event. Studies of the sedimentary environments and habitats in which these beasts lived have been an integral part of a major research project into how, why and under what circumstances this profound step in the evolution of life on Earth occurred. Here, a new palaeogeographic map is constructed from outcrop data integrated with new and archived borehole material. The map shows the extent of a very low-relief coastal wetland developed along the tropical southern continental margin of Laurussia. Coastal floodplains in the Midland Valley and Tweed basins were separated from the marginal marine seaway of the Northumberland–Solway Basin to the south by an archipelago of more elevated areas. A complex mosaic of sedimentary environments was juxtaposed, and included fresh and brackish to saline and hypersaline lakes, a diverse suite of floodplain palaeosols and a persistent fluvial system in the east of the region. The strongly seasonal climate led to the formation of evaporite deposits alternating with flooding events, both meteoric and marine. Storm surges drove marine floods from the SW into both the western Midland Valley and Northumberland–Solway Basin; marine water also flooded into the Tweed Basin and Tayside in the east. The Ballagan Formation is a rare example in the geological record of a tropical, seasonal coastal wetland that contains abundant, small-scale evaporite deposits. The diverse sedimentary environments and palaeosol types indicate a network of different terrestrial and aquatic habitats in which the tetrapods lived.
Longhouses are a key feature of Neolithic Linearbandkeramik (LBK) settlements in Central Europe, but debate persists concerning their usage, longevity and social significance. Excavations at Versend-Gilencsa in south-west Hungary (c. 5200 cal BC) revealed clear rows of longhouses. New radiocarbon dates suggest that these houses experienced short lifespans. This paper produces a model for the chronology of Versend, and it considers the implications of the new date estimates for a fuller understanding of the layout and duration of LBK longhouse settlements.
Capgras delusion is scientifically important but most commonly reported as single case studies. Studies analysing large clinical records databases focus on common disorders but none have investigated rare syndromes.
Identify cases of Capgras delusion and associated psychopathology, demographics, cognitive function and neuropathology in light of existing models.
Combined computational data extraction and qualitative classification using 250 000 case records from South London and Maudsley Clinical Record Interactive Search (CRIS) database.
We identified 84 individuals and extracted diagnosis-matched comparison groups. Capgras was not ‘monothematic’ in the majority of cases. Most cases involved misidentified family members or close partners but others were misidentified in 25% of cases, contrary to dual-route face recognition models. Neuroimaging provided no evidence for predominantly right hemisphere damage. Individuals were ethnically diverse with a range of psychosis spectrum diagnoses.
Capgras is more diverse than current models assume. Identification of rare syndromes complements existing ‘big data’ approaches in psychiatry.
We examined relationships between measures of total knee arthroplasty (TKA) “appropriateness” constructs and surgeon TKA recommendations in people with knee osteoarthritis (OA). Although TKA is highly effective, fifteen to thirty percent of recipients report dissatisfaction and/or little or no symptom improvement. More appropriate selection of surgical candidates may improve both patient outcomes and healthcare resource use, but no validated appropriateness criteria exist currently in Canada.
Patients 30 years of age or older with knee OA referred for surgical consultation at two large joint arthroplasty centres in Alberta, Canada were invited to participate. Participants completed a standardized pre-consult questionnaire, which included the following sociodemographics and validated measures of appropriateness constructs for TKA: knee symptoms; non-surgical management; patient readiness for and expectations of TKA; and net patient benefit. Post-consultation, surgeons were asked to confirm knee OA and their recommendation. We used multivariable logistic regression to examine the relationship between measures of appropriateness constructs and receipt of surgeon TKA recommendation.
Of 3,009 patients approached, 2,360 completed the questionnaire and 2,064 (sixty-nine percent) were eligible at surgical consultation (mean age 65.7 years, standard deviation 9.1; fifty-nine percent were women); 1,495 (seventy-two percent) were recommended for TKA. The likelihood of receiving a TKA recommendation was independently associated with: knee symptoms (odds ratio [OR] per unit increase in pain intensity, 1.19 (95% confidence interval [CI]: 1.11–1.27)); prior non-surgical OA management (OR for prior knee injection, 1.53 (95% CI: 1.21–1.94)); readiness for surgery (OR if definitely/probably willing to undergo TKA, 3.03 (95% CI: 1.99–4.59)); and TKA expectations (OR outcome “very important”: ability to perform daily activities, 1.40 (95% CI: 1.04–1.88); straighten the knee/leg 1.42 (95% CI: 1.13–1.80); participate in exercise/sports 0.75 (95% CI: 0.58–0.98)).
In our cohort of patients with confirmed knee OA who consulted a surgeon for TKA, appropriateness constructs were significantly associated with receipt of a TKA recommendation. Research is ongoing to evaluate the predictive validity of these measures for patient-reported outcomes associated with TKA.
A gap exists between the evidence for reducing risk of knee osteoarthritis (KOA) progression and its application in patients’ daily lives. We aimed to bridge this gap by identifying patient and family physician (FP) self-management priorities to conceptualize and develop a mobile-health application (m-health app). Our co-design approach combined priorities and concerns solicited from patients and FPs with evidence on risk of progression to design and develop a KOA self-management tool.
Parallel qualitative research of patient and FP perspectives was conducted to inform the co-design process. Researchers from the Enhancing Alberta Primary Care Research Networks (EnACT) evaluated the mental models of FPs using cognitive task analysis through structured interviews with four FPs. Using grounded theory methods, patient researchers from the Patient and Community Engagement Research (PaCER) program interviewed five patients to explore their perspectives about needs and interactions within primary care. In three co-design sessions relevant stakeholders (four patients, five FPs, and thirteen researchers) participated to: (i) identify user needs with regard to KOA self-management; and (ii) conceptualize and determine design priorities and functionalities of an m-health app using a modified nominal group process.
Priority measures for symptoms, activities, and quality of life from the user perspective were determined in the first two sessions. The third co-design session with our industry partner resulted in finalization of priorities through interactive patient and FP feedback. The top three features were: (i) a symptoms graph and summary; (ii) information and strategies; and (iii) setting goals. These features were used to inform the development of a minimum viable product.
The novel use of co-design created directive dialog around the needs of patients, highlighting the contrasting views that exist between patients and FPs and emphasizing how exploring these differences might lead to strong design options for patient-oriented m-health apps. Characterizing these disjunctions has important implications for operationalizing patient-centered health care.