To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Lack of knowledge about iodine has been suggested as a risk factor for iodine deficiency in pregnant women, but no studies have addressed this issue in Portugal. So, the aim of this study was to investigate iodine knowledge among Portuguese pregnant women and its association with iodine status. IoMum, a prospective observational study, included 485 pregnant women recruited at Centro Hospitalar e Universitário de S. João, Porto, between the 10th and 13th gestational weeks. Partial scores for knowledge on iodine importance, on iodine food sources or on iodised salt were obtained through the application of a structured questionnaire. Then, a total iodine knowledge score was calculated and grouped into low, medium and high knowledge categories. Urinary iodine concentration (UIC) was measured in spot urine samples by inductively coupled plasma MS. Of the pregnant women, 54 % correctly recognised iodine as important to neurocognitive development, 32 % were unable to identify any iodine-rich food and 71 % presented lack of knowledge regarding iodised salt. Of the women, 61 % had a medium total score of iodine knowledge. Knowledge on iodine importance during pregnancy was positively associated with iodine supplementation and also with UIC. Nevertheless, median UIC in women who correctly recognised the importance of iodine was below the cut-off for adequacy in pregnancy (150 µg/l). In conclusion, knowledge on iodine importance is positively associated with iodine status. Despite this, recognising iodine importance during pregnancy may not be sufficient to ensure iodine adequacy. Literacy-promoting actions are urgently needed to improve iodine status in pregnancy.
The role of milk and dairy products in supplying iodine to pregnant women is unknown in Portugal. The aim of this study was to evaluate the association between milk and dairy product consumption and the iodine status of pregnant women in the IoMum cohort of the Oporto region. Pregnant women were recruited between 10 and 13 weeks of gestation, when they provided a spot urine sample and information on lifestyle and intake of iodine-rich foods. Urinary iodine concentration (UIC) was determined by inductively coupled plasma MS. A total of 468 pregnant women (269 iodine supplement users and 199 non-supplement users) were considered eligible for analysis. Milk (but not yogurt or cheese) intake was positively associated with UIC, in the whole population (P = 0·02) and in the non-supplement users (P = 0·002), but not in the supplement users (P = 0·29). In non-supplement users, adjusted multinomial logistic regression analysis showed that milk consumption <3 times/month was associated with a five times increased risk of having UIC < 50 µg/l when compared with milk consumption ≥2 times/d (OR 5·4; 95 % CI 1·55, 18·78; P = 0·008). The highest UIC was observed in supplement users who reported consuming milk once per d (160 µg/l). Milk, but not yogurt or cheese, was positively associated with iodine status of pregnant women. Despite the observed positive association, daily milk consumption may not be sufficient to ensure adequate iodine intake in this population.
Trematode prevalence and abundance in hosts are known to be affected by biotic drivers as well as by abiotic drivers. In this study, we used the unique salinity gradient found in the south-western Baltic Sea to: (i) investigate patterns of trematode infections in the first intermediate host, the periwinkle Littorina littorea and in the downstream host, the mussel Mytilus edulis, along a regional salinity gradient (from 13 to 22) and (ii) evaluate the effects of first intermediate host (periwinkle) density, host size and salinity on trematode infections in mussels. Two species dominated the trematode community, Renicola roscovita and Himasthla elongata. Salinity, mussel size and density of infected periwinkles were significantly correlated with R. roscovita, and salinity and density correlated with H. elongata abundance. These results suggest that salinity, first intermediate host density and host size play an important role in determining infection levels in mussels, with salinity being the main major driver. Under expected global change scenarios, the predicted freshening of the Baltic Sea might lead to reduced trematode transmission, which may be further enhanced by a potential decrease in periwinkle density and mussel size.
Psychotropic drugs are frequently and sometimes inappropriately used for the treatment of neuropsychiatric symptoms of people with dementia, despite their limited efficacy and side effects. Interventions to address neuropsychiatric symptoms and psychotropic drug use are multifactorial and often multidisciplinary. Suboptimal implementation of these complex interventions often limits their effectiveness. This systematic review provides an overview of barriers and facilitators influencing the implementation of complex interventions targeting neuropsychiatric symptoms and psychotropic drug use in long-term care.
To identify relevant studies, the following electronic databases were searched between 28 May and 4 June: PubMed, Web of Science, PsycINFO, Cochrane, and CINAHL. Two reviewers systematically reviewed the literature, and the quality of the included studies was assessed using the Critical Appraisal Skills Programme qualitative checklist. The frequency of barriers and facilitators was addressed, followed by deductive thematic analysis describing their positive of negative influence. The Consolidated Framework for Implementation Research guided data synthesis.
Fifteen studies were included, using mostly a combination of intervention types and care programs, as well as different implementation strategies. Key factors to successful implementation included strong leadership and support of champions. Also, communication and coordination between disciplines, management support, sufficient resources, and culture (e.g. openness to change) influenced implementation positively. Barriers related mostly to unstable organizations, such as renovations to facility, changes toward self-directed teams, high staff turnover, and perceived work and time pressures.
Implementation is complex and needs to be tailored to the specific needs and characteristics of the organization in question. Champions should be carefully chosen, and the application of learned actions and knowledge into practice is expected to further improve implementation.
Designing complex products involves working with uncertainties as the product, the requirements and the environment in which it is used co-evolve, and designers and external stakeholders make decisions that affect the evolving design. Rather than being held back by uncertainty, designers work, cooperate and communicate with each other notwithstanding these uncertainties by making assumptions to carry out their own tasks. To explain this, the paper proposes an adaptation of Kendall Walton’s make-believe theory to conceptualise designing as playing games of make-believe by inferring what is required and imagining what is possible given the current set of assumptions and decisions, while knowing these are subject to change. What one is allowed and encouraged to imagine, conclude or propose is governed by socially agreed rules and constraints. The paper uses jet engine component design as an example to illustrate how different design teams make assumptions at the beginning of design activities and negotiate what can and cannot be done with the design. This often involves iteration – repeating activities under revised sets of assumptions. As assumptions are collectively revised, they become part of a new game of make-believe in the sense that there is social agreement that the decisions constitute part of the constraints that govern what can legitimately be inferred about the design or added to it.
Contrary to public perception, child sex offending (CSO) and paedophilia are not the same. Only half of all cases of CSO are motivated by paedophilic preference, and a paedophilic preference does not necessarily lead to CSO. However, studies that investigated clinical factors accompanying and contributing to paedophilia so far mainly relied on paedophiles with a history of CSO. The aim of this study was to distinguish between factors associated with sexual preference (paedophile versus non-paedophile) and offender status (with versus without CSO). Accordingly, a 2 (sexual preference) × 2 (offender status) factorial design was used for a comprehensive clinical assessment of paedophiles with and without a history of CSO (n = 83, n = 79 respectively), child sex offenders without paedophilia (n = 32) and healthy controls (n = 148). Results indicated that psychiatric comorbidities, sexual dysfunctions and adverse childhood experiences were more common among paedophiles and child sex offenders than controls. Offenders and non-offenders differed in age, intelligence, educational level and experience of childhood sexual abuse, whereas paedophiles and non-paedophiles mainly differed in sexual characteristics (e.g., additional paraphilias, onset and current level of sexual activity). Regression analyses were more powerful in segregating offender status than sexual preference (mean classification accuracy: 76% versus 68%). In differentiating between offence- and preference-related factors this study improves clinical understanding of both phenomena and may be used to develop scientifically grounded CSO prevention and treatment programmes. It also highlights that some deviations are not traceable to just one of these two factors, thus raising the issue of the mechanism underlying both phenomena.
Optimism is associated with reduced cardiovascular disease risk; however, few prospective studies have considered optimism in relation to hypertension risk specifically. We investigated whether optimism was associated with a lower risk of developing hypertension in U.S. service members, who are more likely to develop high blood pressure early in life. We also evaluated race/ethnicity, sex and age as potential effect modifiers of these associations.
Participants were 103 486 hypertension-free U.S. Army active-duty soldiers (mean age 28.96 years, 61.76% White, 20.04% Black, 11.01% Hispanic, 4.09% Asian, and 3.10% others). We assessed optimism, sociodemographic characteristics, health conditions, health behaviours and depression status at baseline (2009–2010) via self-report and administrative records, and ascertained incident hypertension over follow-up (2010–2014) from electronic health records and health assessments. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and adjusted models for a broad range of relevant covariates.
Over a mean follow-up of 3.51 years, 15 052 incident hypertension cases occurred. The highest v. lowest optimism levels were associated with a 22% reduced risk of developing hypertension, after adjusting for all covariates including baseline blood pressure (HR = 0.78; 95% CI = 0.74–0.83). The difference in hypertension risk between the highest v. lowest optimism was also maintained when we excluded soldiers with hypertension in the first two years of follow-up and, separately, when we excluded soldiers with prehypertension at baseline. A dose–response relationship was evident with higher optimism associated with a lower relative risk (p < 0.001). Higher optimism was consistently associated with a lower risk of developing hypertension across sex, age and most race/ethnicity categories.
In a diverse cohort of initially healthy male and female service members particularly vulnerable to developing hypertension, higher optimism levels were associated with reduced hypertension risk independently of sociodemographic and health factors, a particularly notable finding given the young and healthy population. Results suggest optimism is a health asset and a potential target for public health interventions.
The molybdenum disulfide (MoS2) and indium tin oxide (ITO) interface were studied by atom probe tomography (APT). Raman spectroscopy, scanning electron microscopy, and grazing-incidence x-ray diffraction measurements were performed as complementary characterization. Results confirm that nanowires plated shape with the 〈110〉-orientation are aligned perpendicular to the ITO film with principal reflections at (002), (100), (101), (201), and Raman spectroscopy vibrational modes at E12g at 378 cm−1 and A1g at 407 cm−1 correspond to 2H-MoS2. APT reveals MoS+2, MoS+3 as predominant evaporated molecular ions on the sample, indicating no significant diffusion/segregation of Mo or S species within the ITO layer.
Before drawing conclusions on the contribution of an effective intervention to daily practice and initiating dissemination, its quality and implementation in daily practice should be optimal. The aim of this process evaluation was to study these aspects alongside a randomized controlled trial investigating the effects of a multidisciplinary biannual medication review in long-term care organizations (NTR3569).
Process evaluation with multiple measurements.
Thirteen units for people with dementia in six long-term care organizations in the Netherlands.
Physicians, pharmacists, and nursing staff of participating units.
The PROPER intervention is a structured and biannually repeated multidisciplinary medication review supported by organizational preparation and education, evaluation, and guidance.
Web-based questionnaires, interviews, attendance lists of education sessions, medication reviews and evaluation meetings, minutes, evaluation, and registration forms.
Participation rates in education sessions (95%), medication reviews (95%), and evaluation meetings (82%) were high. The intervention’s relevance and feasibility and applied implementation strategies were highly rated. However, the education sessions and conversations during medication reviews were too pharmacologically oriented for several nursing staff members. Identified barriers to implementation were required time, investment, planning issues, and high staff turnover; facilitators were the positive attitude of professionals toward the intervention, the support of higher management, and the appointment of a local implementation coordinator.
Implementation was successful. The commitment of both higher management and professionals was an important factor. This may partly have been due to the subject being topical; Dutch long-term-care organizations are pressed to lower inappropriate psychotropic drug use.
The START (STrAtegies for RelaTives) intervention reduced depressive and anxiety symptoms of family carers of relatives with dementia at home over 2 years and was cost-effective.
To assess the clinical effectiveness over 6 years and the impact on costs and care home admission.
We conducted a randomised, parallel group, superiority trial recruiting from 4 November 2009 to 8 June 2011 with 6-year follow-up (trial registration: ISCTRN 70017938). A total of 260 self-identified family carers of people with dementia were randomised 2:1 to START, an eight-session manual-based coping intervention delivered by supervised psychology graduates, or to treatment as usual (TAU). The primary outcome was affective symptoms (Hospital Anxiety and Depression Scale, total score (HADS-T)). Secondary outcomes included patient and carer service costs and care home admission.
In total, 222 (85.4%) of 173 carers randomised to START and 87 to TAU were included in the 6-year clinical efficacy analysis. Over 72 months, compared with TAU, the intervention group had improved scores on HADS-T (adjusted mean difference −2.00 points, 95% CI −3.38 to −0.63). Patient-related costs (START versus TAU, respectively: median £5759 v. £16 964 in the final year; P = 0.07) and carer-related costs (median £377 v. £274 in the final year) were not significantly different between groups nor were group differences in time until care home (intensity ratio START:TAU was 0.88, 95% CI 0.58–1.35).
START is clinically effective and this effect lasts for 6 years without increasing costs. This is the first intervention with such a long-term clinical and possible economic benefit and has potential to make a difference to individual carers.
Declarations of interest
G.L., Z.W. and C.C. are supported by the UCLH National Institute for Health Research (NIHR) Biomedical Research Centre. G.L. and P.R. were in part supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart's Health NHS Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Z.W. reports during the conduct of the study; personal fees from GE Healthcare, grants from GE Healthcare, grants from Lundbeck, other from GE Healthcare, outside the submitted work.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.
The introduction of fast-track licensing strategies increases the approval of anti-cancer drugs with ambiguous benefit-risk profiles. Thus, in many instances there is lacking evidence about overall survival (OS) at the time of marketing authorisation. Our objective was to monitor and characterise therapies with ambiguous benefit-risk profiles and identify any post-approval updates on median OS after at least three years of approval by the European Medicines Agency (EMA).
We included all originator anti-cancer drugs with initially ambiguous benefit-risk profiles that received marketing authorization from the EMA between 1 Jan 2009 and 31 May 2015. Our monitoring timeframe was at least three years after EMA-approval. To identify study updates, the following three sources were included: clinicaltrials.gov, European Public Assessment Reports (EPARs), and PubMed.
In total, we identified 102 eligible approval studies. Out of these, a negative difference in median OS or no information was available in forty-three (42.2%) instances. During monitoring, eleven updates with accessible information on median OS could be identified. Including monitoring results, there are still thirty-two remaining therapies (31.4%) where no or negative information (n = 27 [26.5%] and n = 5 [4.9%], respectively) regarding median OS was present at least three years after EMA approval.
One-third of oncology drugs with ambiguous benefit-risk profiles failed to demonstrate a survival benefit even several years following marketing authorization. Systematic and transparent post-approval monitoring mechanisms will be of high relevance to assure a clinically relevant patient benefit, since the trend towards faster access to medicines with uncertain benefit is increasing rather than declining.
The aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.
To explore the association between anxiety and future dementia.
Medline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.
Anxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).
Anxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.
We present very detailed images of the photosphere of an AGB star obtained with the PIONIER instrument, installed at the Very Large Telescope Interferometer (VLTI). The images show a well defined stellar disc populated by a few convective patterns. Thanks to the high precision of the observations we are able to derive the contrast and granulation horizontal scale of the convective pattern for the first time in a direct way. Such quantities are then compared with scaling relations between granule size, effective temperature, and surface gravity that are predicted by simulations of stellar surface convection.
We studied the patient and non-patients factors of inappropriate psychotropic drug (PD) prescription for neuropsychiatric symptoms (NPS) in nursing home patients with severe dementia.
In a cross-sectional study, the appropriateness of prescriptions was explored using the Appropriate Psychotropic drug use In Dementia (APID) index sum score. This index assesses information from medical records on indication, evaluation, dosage, drug–drug interactions, drug–disease interactions, duplications, and therapy duration. Various measurements were carried out to identify the possible patient and non-patient factors. Linear multilevel regression analysis was used to identify factors that are associated with APID index sum scores. Analyses were performed for groups of PDs separately, i.e. antipsychotics, antidepressants, anxiolytics, and hypnotics.
The sample consisted of 338 patients with a PD prescription that used 147 antipsychotics, 167 antidepressants, 85 anxiolytics, and 76 hypnotics. It was found that older patients and more severe aggression, agitation, apathy, and depression were associated with more appropriate prescriptions. Additionally, less appropriate prescriptions were found to be associated with more severe anxiety, dementia diagnoses other than Alzheimer dementia, more physician time available per patient, more patients per physician, more years of experience of the physician, and higher nurse's workload.
The association of more pronounced NPS with more appropriate PD prescriptions implies that physicians should pay more attention to the appropriateness of PD prescriptions when NPS are less manifest. Non-patient-related factors are also associated with the appropriateness of PD prescriptions. However, especially considering that some of these findings are counter-intuitive, more research on the topic is recommended.
Objectives: Pedophilia (P) is a psychiatric disease associated with sexual attraction toward children and often accompanied by child sexual offending (CSO). Consequently, it is important to address the understanding of executive dysfunctions that may increase the probability of CSO. Moreover, this research field has been lacking to disentangle executive deficits associated with pedophilia (as a deviant sexual preference) from those associated with CSO (as a deviant sexual behavior). Methods: The German multi-sided research network NeMUP offers the opportunity to overcome these limitations. By applying the Cambridge Automated Neuropsychological Test Battery in four carefully matched groups of men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual offending against children; (3) child molesters without pedophilia (N=19), and (4) non-offending controls (N=49), we were able to analyze executive functioning in pedophilia and CSO independently. Results: Both CSO groups as compared to both non-CSO groups exhibited worsened response inhibition ability. However, only non-pedophilic offenders showed additionally disabled strategy use ability. Regarding set-shifting abilities, the P+CSO group showed the best performance. We also found that performances were affected by age: only in pedophiles, response inhibition worsened with age, while age-related deficits in set-shifting abilities were restricted to non-pedophilic participants. The latter also differentiated between both sexual preference groups. Conclusions: Our results are the first to demonstrate that executive dysfunctions are related to offense status rather than pedophilic preference. Furthermore, there was evidence for differentiating age and performance correlations between pedophiles and non-pedophiles, which warrants further investigation. (JINS, 2017, 23, 460–470)