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Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacological treatment for obsessive–compulsive disorder (OCD). However, insufficient response is common and it remains unclear whether specific patient-level factors influence the likelihood of treatment response.
Aims
To determine the efficacy and acceptability of SSRIs in adult OCD, and to identify patient-level modifiers of efficacy.
Methods
We conducted an individual patient data meta-analysis (IPDMA) of industry-sponsored short-term, randomised, placebo-controlled SSRI trials submitted for approval to the Dutch regulatory agency to obtain marketing approval for treating OCD in adults. We performed a two-stage meta-analysis, using crude data of available trials. The primary outcome was the difference in Yale–Brown Obsessive–Compulsive Scale (YBOCS) change between active treatment and placebo. Secondary outcomes were differences in response (defined as the odds ratio of ≥35% YBOCS point reduction) and acceptability (defined as the odds ratio for all-cause discontinuation). We examined the modifying effect of baseline characteristics: age, gender, illness severity, depressive symptoms, weight, illness duration and history of antidepressant use.
Results
After excluding three trials because of missing data, we analysed results from 11 trials (79% of all submitted trials, n = 2372). The trial duration ranged from 10 to 13 weeks. Mean difference of SSRIs relative to placebo was 2.65 YBOCS points (95% CI 1.85–3.46, p < 0.0001), equalling a small effect size (0.33 Hedges’ g). The odds ratio for response was 2.21 in favour of active treatment (95% CI 1.72–2.83, p < 0.0001), with a number needed to treat of seven. Patient characteristics did not modify symptom change or response. Acceptability was comparable for SSRIs and placebo.
Conclusions
Our IPDMA showed that SSRIs are well accepted and superior to placebo for treating OCD. The effects are modest and independent of baseline patient characteristics.
[What is the driving force behind Japan's policy in the Middle East? Can it be summed up in one word, oil? Is Japan essentially the lapdog of the United States, or has it established an independent position on contentious issues in the region such as the Israel-Palestine conflict, the Iraq War, and Iran's nuclear development? Raquel Shaoul and John de Boer take up these questions in two articles as they evaluate Japan's impact on the Middle East.]
“Israel and Japan are situated at opposite ends of Asia, but this is a fact which binds them together rather than separates them. The vast continent of Asia is their connecting link, and the consciousness of their Asian destiny is their common thought.”
In November 2023, the Department of Health and Social Care published guidance, entitled ‘Baroness Hollins’ Final Report: My Heart Breaks – Solitary Confinement in Hospital Has no Therapeutic Benefit for People with a Learning Disability and Autistic People’. The report's commendable analysis of the problems and identification of the areas where practice should be improved is unfortunately not matched by many of its recommendations, which appear to be contrary to evidence-based approaches. The concerns are wide-ranging, from the use of the term ‘solitary confinement’ for current long-term segregation (LTS) and seclusion, to presumption that all LTS and seclusion is bad, to holding clinicians (mainly psychiatrists) responsible for events beyond their locus of control. Importantly, there is a no guidance on how to practically deliver the recommendations in an evidence-based manner. This Feature critically appraises the report, to provide a comprehensive summary outlining potential positive impacts, identifying specific concerns and reflecting on best practice going forward.
Luminescence dating methods are widely used to date coastal sediments, while luminescence tracing methods are an upcoming approach to reconstruct coastal sediment pathways. Both methods rely on subaqueous resetting (bleaching) of luminescence signals and would benefit from quantification of this process in the natural coastal environment. We describe the set-up and outcomes of an in situ subaqueous bleaching experiment for luminescence signals of K-feldspar grains in the Dutch Wadden Sea. We deployed a full-day bleaching field experiment with irradiated feldspar samples tethered to a pole at various positions within and above the water column to quantify (1) the bleaching potential, that is, the light intensity and spectrum as a function of time, depth and tidal stage, and (2) the bleaching efficiency, that is, the degree of bleaching of infrared stimulated luminescence (IRSL) and post-infrared IRSL (pIRIR) signals measured at 150, 225 and 290°C after a full day of light exposure above and below water. Our bleaching-potential results show that the strongest subaqueous light attenuation took place during low tide when sediment concentrations are the highest. We also observed stronger attenuation of the ultraviolet part of the spectrum compared to other parts of the spectrum. Our bleaching-efficiency results show that bleaching reduces with depth, that pIRIR signals bleach slower than IRSL signals underwater and that bleaching efficiency reduces with pIRIR measurement temperature. None of the investigated signals were fully reset after 13.5 hours of light exposure, even for subaerially exposed samples. Our work provides the first quantitative data on pIRIR bleaching in a natural subaqueous environment, which is relevant for K-feldspar-based luminescence dating and tracing applications.
There are both negative and positive stereotypes about public sector workers. Most studies focus on negative stereotypes, like the idea that public servants are lazy. We, however, do the opposite. We focus on a positive stereotype: public sector workers are seen as caring and helpful. We test the effects of positive stereotypes on the quality of public service delivery. Using a pre-registered audit experiment in elderly care in the Netherlands and Belgium, we find that activating a pro-social stereotype does not affect the outcome of public service quality in terms of response rate and information provision. However, it does improve the bureaucratic process: public sector workers are friendlier toward citizens. They say around 12% more ‘thank you’ in their replies. Moreover, the citizens’ gender affects the response rate: female citizens receive around 10% more replies. Concluding, we show that positive stereotyping can improve parts of the quality of public service delivery but not all.
The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID).
Methods
We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as “minimal improvement”).
Results
We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4–5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms.
Conclusions
By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.
Higher intensity of psychotherapy might improve treatment outcome in depression, especially in those with comorbid personality disorder.
Aims
To compare the effects of 25 individual sessions (weekly) of two forms of psychotherapy – short-term psychoanalytic supportive psychotherapy (SPSP) and schema therapy – with the same treatments given for 50 sessions (twice weekly) in people with depression and personality disorder. Trial registration: NTR5941.
Method
We conducted a pragmatic, double-randomised clinical trial and, over 37 months, recruited 246 adult out-patients with comorbid depression/dysthymia and personality disorder. A 2 × 2 factorial design randomised participants to 25 or 50 sessions of SPSP or schema therapy. The primary outcome was change in depression severity over 1 year on the Beck Depression Inventory II (BDI-II). Secondary outcomes were remission both of depression and personality disorder.
Results
Compared with 25 sessions, participants who received 50 sessions showed a significantly greater decrease in depressive symptoms over time (time × session dosage, P < 0.001), with a mean difference of 5.6 BDI points after 1 year (d = −0.53, 95% CI −0.18 to 0.882, P = 0.003). Remission from depression was also greater in the 50-session group (74% v. 58%, P = 0.025), as was remission of personality disorder (74% v. 56%, P = 0.010).
Conclusions
Greater intensity of psychotherapy leads to better outcomes of both depression and personality status in people with comorbid depression and personality disorder.
Felt presence is a widely occurring experience, but remains under-recognised in clinical and research practice. To contribute to a wider recognition of the phenomenon, we aimed to assess the presentation of felt presence in a large population sample (n = 10 447) and explore its relation to key risk factors for psychosis. In our sample 1.6% reported experiencing felt presence in the past month. Felt presence was associated with visual and tactile hallucinations and delusion-like thinking; it was also associated with past occurrence of adverse events, loneliness and poor sleep. The occurrence of felt presence may function as a marker for general hallucination proneness.
My response to Gabriele Gava’s Kant’s Critique of Pure Reason and the Method of Metaphysics (2023) focuses on Kant’s conception of the role of critique in the Critique of Pure Reason. On my account, Gava’s emphasis on the constructive elements of the Critique downplays the critique of former metaphysics elaborated in all three parts of the Transcendental Doctrine of Elements. After some comments on Kant’s conception of the Critique as a doctrine of method, I support this view by discussing the relation between transcendental philosophy and transcendental critique, Kant’s analysis of the faculties, and his transcendental deduction of space.
The independence polynomial originates in statistical physics as the partition function of the hard-core model. The location of the complex zeros of the polynomial is related to phase transitions, and plays an important role in the design of efficient algorithms to approximately compute evaluations of the polynomial.
In this paper we directly relate the location of the complex zeros of the independence polynomial to computational hardness of approximating evaluations of the independence polynomial. We do this by moreover relating the location of zeros to chaotic behaviour of a naturally associated family of rational functions; the occupation ratios.
Edited by
Dennis S. Chi, Memorial Sloan-Kettering Cancer Center, New York,Nisha Lakhi, Richmond University Medical Center, Staten Island,Nicoletta Colombo, University of Milan-Bicocca
Locally advanced endometrial cancer is associated with high-risk of both local pelvic and systemic recurrence. Radiotherapy has been traditionally used after surgery in this patient population, however the substantial risk of systemic metastases undermines clinical outcomes of women treated with local modality treatment alone. Thus, combination chemo-radiotherapy seems a logical approach aiming to reduce the risk of both local and distant failure. Investigated in multiple institutional and cooperative group trials, the use of chemoradiation in this patient group yields failure-free survival rates exceeding 60% at three years. However, patients treated with this approach pay a high price in both acute and late toxicity. In a recently reported randomized phase III trial, use of single chemotherapy strategy was less toxic and not inferior to the combined chemoradiotherapy approach. Based on this evidence, systemic chemotherapy alone is the preferred treatment strategy for women with stage III endometrial cancer.
International psychosocial support guidelines reflect consensus on support principles and interventions. However, no consensus exists on what recipients consider important elements of service delivery. Within two contexts – after a potentially traumatic event (PTE) and people with Spinal Muscular Atrophy (SMA)–the aims were to contribute to (1) understanding which psychosocial support aspects are considered important by recipients and relevant stakeholders; (2) developing instruments to test and integrate those aspects in practice, in order to evaluate the quality of psychosocial support from the recipient’s perspective.
Method:
Concept mapping was used to achieve consensus on key themes of psychosocial support. These were operationalized in surveys and pilot-tested, conforming to the Consumer Quality Index. This determines the importance and needs for improvement.
Results:
Concept mapping resulted in eight key themes within the PTE context and six in the SMA context. PTE survey (N= 132) results showed key themes “an approach that starts from the needs and capacities of the affected one” and “monitoring individuals affected and initiating follow-up where needed” were most important. Key theme “providing information on common emotional reactions” received the highest score of perceived need for improvement. SMA survey (N= 57) results showed key themes “an approach that incorporates all aspects of a human being” and “a respectful approach and awareness of personal boundaries” as most important. The perceived need for improvement of the key theme “availability and accessibility of quality information” was ranked the highest.
Conclusion:
The similarities between both contexts support the notion that there are universal aspects of psychosocial support. Simultaneously, the context-specific idiosyncrasies found underscore the necessity to adapt to context. The surveys have the potential to contribute to a growing toolbox of quality evaluation instruments.
Responding to mistrust in the European agencies’ risk assessments in politically salient cases, the European Union (EU) legislator, the European Food Safety Authority and the European Medicines Agency alike have accelerated their efforts to foster EU regulatory science transparency. These simultaneous endeavours have, however, taken place in a fragmented legislative and administrative context, with each agency operating under a different legal framework. By focusing on authorisation procedures, from registration of studies to authorisation of novel foods, pesticides and human medicines, this article examines the resulting regimes governing the disclosure of scientific data by EU agencies to identify common trends and sectoral specificities. Against the background of an overall shift towards enhanced transparency, we shed light on, first, the circulation of institutional arrangements and practices among agencies and, second, the new dimensions of transparency emerging from these developments. We also highlight the remaining sectoral differences and argue that they could have potentially large impacts on the amount and type of information disclosed and on the level of transparency perceived by stakeholders and citizens. We argue that more coherence across the sectoral transparency regimes is needed, in particular in light of the agencies’ contested legitimacy and of their increasing cooperation on cross-cutting issues like antimicrobial resistance and medicine and pesticide residues in food.
Biotelemetry is a useful tool for the simultaneous measurement of several physiological and behavioural parameters in non-restrained, freely moving animals. However, the weight and volume of the implanted intra-abdominal transmitter may cause discomfort. The aim of this study was to assess body weight and behaviour of BALB/c and 129/Sv mice after implantation of an intra-abdominal transmitter. In order to measure more detailed behaviour, the automated behaviour observation analysis system (LABORAS™) was used. During the first days after surgery, body weight and the behaviours of climbing, locomotion and eating were found to decrease in both strains, whereas grooming and immobility increased. These changes were more pronounced in the transmitter animals than in the sham operated animals, however, indicating a temporary impairment in well-being. Within two weeks after surgery, the animals seemed to have fully recovered.
There is continuing debate about the space needs and requirements of broiler chickens, The aims of this study were to measure the amount of floor area a six-week-old broiler occupies for different behaviours and to use the obtained results in two models to estimate the number of birds that can be kept per m2 in large flocks simulating different levels of behavioural synchronisation. Photographs were taken of overhead projections of broilers (2.468 kg on average) kept in floor pens of 1 m2 with either eight (low density) or 16 birds (high density) per pen. Individual body space was measured from these photographs for seven behaviours. Posture and density affected body space of the behaviours idle, drinking, and ground pecking. The first model, computing space needed per bird performing a behaviour in relation to flock size, showed that 15.3-15.7 birds m−2 (37.8-38.7 kg m−2) can be housed maximally, based on low density measurements and 18.5-19.4 birds m−2 (45.7-47.9 kg m−2) based on high density measurements. The second model, computing stocking density based on synchronisation of behaviour and body space, showed that 13.7-15.9 birds m−2 (33.8-39.2 kg m−2) can be housed maximally based on low density measurements and 15.4-18.6 birds m−2 (38.0-45.9 kg m−2) based on high density measurements. Results based on high density measurements implied that birds are compressed. Given the restrictions of a limited number of behaviours and no inclusion of movement and social interactions in the models of this study, stocking density in large flocks should not exceed 16 birds m−2 (39.4 kg) because that would lead to compression of birds which will suppress opportunities for behavioural expression and therefore impair welfare.
The Welfare Quality® (WQ) protocols are increasingly used for assessing welfare of farm animals. These protocols are time consuming (about one day per farm) and, therefore, costly. Our aim was to assess the scope for reduction of on-farm assessment time of the WQ protocol for dairy cattle. Seven trained observers quantified animal-based indicators of the WQ protocol in 181 loose-housed and 13 tied Dutch dairy herds (herd size from 10 to 211 cows). Four assessment methods were used: avoidance distance at the feeding rack (ADF, 44 min); qualitative behaviour assessment (QBA, 25 min); behavioural observations (BO, 150 min); and clinical observations (CO, 132 min). To simulate reduction of on-farm assessment time, a set of WQ indicators belonging to one assessment method was omitted from the protocol. Observed values of omitted indicators were replaced by predictions based on WQ indicators of the remaining three assessment methods, resources checklist, and interview, thus mimicking the performance of the full WQ protocol. Agreement between predicted and observed values of WQ indicators, however, was low for ADF, moderate for QBA, slight to moderate for BO, and poor to moderate for CO. It was concluded that replacing animal-based WQ indicators by predictions based on remaining WQ indicators shows little scope for reduction of on-farm assessment time of the Welfare Quality® protocol for dairy cattle. Other ways to reduce on-farm assessment time of the WQ protocol for dairy cattle, such as the use of additional data or automated monitoring systems, should be investigated.
The aim of this study was to develop a welfare assessment protocol using different indicators, for pre-weaned dairy calves, that is feasible and time efficient. To this end, the protocol had to combine animal-based indicators (measurements on physiology, general appearance and behaviour) providing the basis for welfare assessment, with resource-based indicators (measurements on management and the environment) providing the basis for identifying risk factors. Indicators, both animal-and resource-based, were selected by a review of existing literature and a process of expert consultation. Following the formulation phase, the protocol was then applied on five Irish dairy farms to develop further for completeness and on-farm feasibility. After each on-farm application, the protocol was critically evaluated, and modifications were made accordingly. Upon completion of the on-farm application phase, a feasible, reliable and time-efficient protocol was produced.
Qualitative Behaviour Assessment (QBA) is part of the Welfare Quality® protocol for dairy cattle, although its inter- and intra-observer reliability have not been reported. This study evaluated inter- and intra-observer reliability of the QBA for dairy cattle in experienced and inexperienced observers using videos. Eight experienced observers performed the QBA (20 descriptors) twice for 16 video clips (60 s per clip; series 1) showing 4-17 animals. They assessed another 11 video clips showing herds (4 shots of 30 s per clip; series 2). Ten inexperienced observers performed the QBA on both video series one time. Inter-observer reliability of experienced observers ranged from slight to moderate (both assessments of series 1), and from low to high (series 2) for descriptors, and from slight to moderate for the QBA score. Inter-observer reliability of inexperienced observers ranged from low to moderate (series 1), and from low to high (series 2) for descriptors, and was moderate (both series) for the QBA score. Intra-observer correlations varied largely per descriptor and observer. They were both negative and positive, and ranged from low to very high. High correlations, however, were not necessarily associated with low paired differences. Values of half of the descriptors and the QBA score differed amongst experienced and inexperienced observers. The QBA appears insufficiently reliable as a tool for welfare assessment in dairy cattle.