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Over the last decade, the Supreme Court of Pakistan has emerged as a powerful and overtly political institution. While the strong form of judicial review adopted by the Supreme Court has fostered the perception of a sudden and ahistorical judicialisation of politics, the judiciary's prominent role in adjudicating issues of governance and statecraft was long in the making. This book presents a deeply contextualised account of law in Pakistan and situates the judicial review jurisprudence of the superior courts in the context of historical developments in constitutional politics, evolution of state structures and broader social transformations. This book highlights that the bedrock of judicial review has remained in administrative law; it is through the consistent development of the 'Writ jurisdiction' and the judicial review of administrative action that Pakistan's superior courts have progressively carved an expansive institutional role and aggrandised themselves to the status of the regulator of the state.
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurity that typically develops after the administration of infant formula, suggesting a link between nutritional components and disease development. One of the most significant complications that develops in patients with NEC is severe lung injury. We have previously shown that the administration of a nutritional formula that is enriched in pre-digested triglycrides that do not require lipase action can significantly reduce the severity of NEC in a mouse model. We now hypothesize that this 'pre-digested fat system (PDF)' may reduce NEC-associated lung injury. In support of this hypothesis, we now show that rearing newborn mice on a nutritional formula based on the 'pre-digested fat (PDF) system’ promotes lung development, as evidenced by increased tight junctions and surfactant protein expression. Mice who were administered this 'PDF fat system’ were significantly less vulnerable to the development of NEC-induced lung inflammation, and the administration of the 'PDF fat system’ conferred lung protection. In seeking to define the mechanisms involved, the administration of the PDF system’ significantly enhanced lung maturation and reduced the production of reactive oxygen species (ROS). These findings suggest that the PDF system protects the development of NEC-induced lung injury through effects on lung maturation and reduced reactive oxygen species in the lung, and also increase lung maturation in non-NEC mice.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms.
The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test–retest reliability was assessed with 264 participants.
An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24–5.43; distress: a = 1.60–5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test–retest reliability, and validity.
The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.
DSM-V describes three eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder), three feeding disorders (avoidant/restrictive food intake disorder, pica, and rumination disorder), and two residual feeding and eating disorder categories (APA, 2013). Although these disorders contain some overlapping features, an individual can receive just one feeding or eating disorder diagnosis at a time. The only exception is pica, which can be diagnosed concurrently with another feeding or eating disorder if the pica behavior is severe enough to warrant additional clinical attention.
With regard to the currently perceptible technological, social and economic change, also known as the “Fourth Industrial Revolution” or “Internet of Things”, small and medium-sized enterprises (SMEs) in particular are confronted with various obstacles in their attempt of keeping pace. For example, there is a lack of orientation of which I4.0 technology is suitable for a target-oriented application. Furthermore, the actual or potential effects of I4.0 can only be estimated insufficiently and SMEs are at a disadvantage compared to large companies due to lower monetary and personnel capacities. In this publication these obstacles on the way to become an I4.0 company are taken up and the core elements of a methodical solution approach in the form of the “Potential Model” are explained in detail. Thereby the Potential Model is intended to support SMES at the rough-quantitative evaluation of I4.0 and the development of I4.0 implementation strategies with minimal monetary and time-related efforts needed.
In addition to the development and research of battery-driven vehicles, a high research effort in the field of hydrogen technology can currently be observed. Various research and strategy initiatives relating to hydrogen are being initiated and pursued with considerable commitment worldwide. A significant expansion of the hydrogen filling station network is also being sought in Germany. In the course of designing a hydrogen refuelling station, the paradigms of thermal management must be taken into account in addition to a large number of different environmental and life phase-induced influencing factors. The interactions between influencing factors, requirements and the system architecture result in a multitude of possible refuelling station concepts, which can hardly be surveyed or managed from an organisational point of view. This publication introduces a method for the development of descriptive requirement collectives, which is applied to hydrogen refuelling stations in the framework of THEWA, but can also be adapted for other technical systems. The requirement collective is the first core element of the THEWA tool chain that enables a requirement-oriented and fast design of hydrogen refuelling stations.
Through consultation with foundation doctors on their psychiatry placements in Leeds, we established that they didn't feel the trustwide teaching programme met their needs, with them rating the relevance as 5.8 on a 1-10 Likert scale. They also reported their access to formal and informal teaching had been limited by COVID-19 restrictions. We aimed to create an accessible teaching programme that met their developmental needs as set out by the Foundation curriculum, as well as their confidence and skill set in dealing with common mental health presentations. Our supplementary aims were to promote psychiatry as a career and to provide supervised teaching opportunities to core trainees.
Having assessed the foundation doctors confidence in dealing with different scenarios, we created a 9 week teaching programme covering common mental health presentations they're likely to encounter during their training. The virtual sessions focus on what assessment and management skills would be expected for a foundation doctor, as well as when and how to access support and refer on. The programme was designed to be trainee led with the teaching being facilitated by core trainees as it was felt that they would best relate to the experiences and developmental needs of foundation doctors. This also provided the CTs with an opportunity to develop their teaching skills, something that has become more difficult during COVID.
Through weekly feedback of the sessions we were able to demonstrate that for 8 of the 9 sessions the foundation doctors rated them as being ‘useful’ or ‘very useful’ and we're currently reviewing the topic and materials for the outlying session.
Through self-assessed ratings before and after the programme, we demonstrated significant increases in confidence in dealing with all 9 of the scenarios. All of the foundation doctors indicated that they had found the programme beneficial.
As shown in the results, the programme has been well received by the foundation doctors who's confidence in dealing with a range of scenarios has improved. The programme has also been well received by the trust who have asked us to repeat the it for future foundation rotations and by core trainees who were grateful of the development opportunities that this provided. Further developments will include extending the programme for the duration of the placement to enable us to cover an enhanced range of presentations and to consolidate core skills.
Violent criminal offenders with personality disorders (PD's) can cause immense harm, but are often deemed untreatable. This study aimed to conduct a randomized clinical trial to test the effectiveness of long-term psychotherapy for rehabilitating offenders with PDs.
We compared schema therapy (ST), an evidence-based psychotherapy for PDs, to treatment-as-usual (TAU) at eight high-security forensic hospitals in the Netherlands. Patients in both conditions received multiple treatment modalities and differed only in the individual, study-specific therapy they received. One-hundred-three male offenders with antisocial, narcissistic, borderline, or paranoid PDs, or Cluster B PD-not-otherwise-specified, were assigned to 3 years of ST or TAU and assessed every 6 months. Primary outcomes were rehabilitation, involving gradual reintegration into the community, and PD symptoms.
Patients in both conditions showed moderate to large improvements in outcomes. ST was superior to TAU on both primary outcomes – rehabilitation (i.e. attaining supervised and unsupervised leave) and PD symptoms – and six of nine secondary outcomes, with small to moderate advantages over TAU. ST patients moved more rapidly through rehabilitation (supervised leave, treatment*time: F(5308) = 9.40, p < 0.001; unsupervised leave, treatment*time: F(5472) = 3.45, p = 0.004), and showed faster improvements on PD scales (treatment*time: t(1387) = −2.85, p = 0.005).
These findings contradict pessimistic views on the treatability of violent offenders with PDs, and support the effectiveness of long-term psychotherapy for rehabilitating these patients, facilitating their re-entry into the community.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.
Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.
Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.
These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.
North-western Arabia is marked by thousands of prehistoric stone structures. Of these, the monumental, rectilinear type known as mustatils has received only limited attention. Recent fieldwork in AlUla and Khaybar Counties, Saudi Arabia, demonstrates that these monuments are architecturally more complex than previously supposed, featuring chambers, entranceways and orthostats. These structures can now be interpreted as ritual installations dating back to the late sixth millennium BC, with recent excavations revealing the earliest evidence for a cattle cult in the Arabian Peninsula. As such, mustatils are amongst the earliest stone monuments in Arabia and globally one of the oldest monumental building traditions yet identified.
Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.