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The requirements on validity for studies in design research are very high. Therefore, this paper aims at identifying challenges that occur when setting up studies and suggests solution strategies to address them. Three different institutes combining their experience discussed several studies in a workshop. Resulting main challenges are to find a suitable task, to operationalise the variables and to deal with a high analysis effort per participant. Automation in data evaluation and a detailed practical guideline on studies in design research are considered necessary.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly (e.g. increased interleukin-6 and tumour necrosis factor-alpha). COX-2 inhibitors down-regulate increased inflammatory markers and are therefore investigated as an add-on therapy in depression. Proinflammatory cytokines and/or kynurenine metabolites may predict the outcome of treatment with COX-2 inhibitors.
To prove or disapprove the hypothesis of a better therapy response in the group of add-on celecoxib to sertraline, particularly in patients with a more pronounced proinflammatory state at baseline. The aim is to find a biological predictor (cytokines and/or kynurenine metabolites) for treatment outcome.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study. It investigates the mean change in clinical outcome and in serum cytokine and kynurenine levels from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with sertraline plus celecoxib versus sertraline plus placebo for six weeks. 51 depressed patients of both gender, aged between 18 and 60 years without any recent inflammatory disease were enrolled. The study comprises six study visits (6x ratings, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. Cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA), kynurenine and its metabolites by High Performance Liquid Chromatography (HPLC).
Results and Conclusion
The study was completed quite recently and the results are in progress.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome.
To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline.
Results and Conclusion
The study was completed quite recently and the results are in progress.
In a study conducted in the database of a large commercial healthcare insurer, we previously demonstrated that use of a commercial pharmacogenetic assay for individuals with mood disorders was associated with decreased resource utilization and cost in the 6 month period following use compared to propensity-score matched controls. We conducted a post hoc analysis to understand variables associated with high cost savings.
The results and methods of the initial study have previously been described. Cases were individuals with mood and anxiety disorders who received a commercial pharmacogenetic assay (Genomind, King of Prussia PA) to inform pharmacotherapy. 817 tested individuals (cases) with mood and/or anxiety disorders were matched to 2745 controls. Overall costs were estimated to be $1,948 lower in the tested group. The differences were largely the result of lesser emergency room and inpatient utilization for cases. In the present analysis, cost difference for cases compared to their matched controls was rank ordered by decile. High cost savers were arbitrarily defined a priori as the top 20% of savers. Using multivariable modeling techniques, an ordinal logistic regression model was generated in which baseline or follow-up variables were statistically tested for independent associations with high, low, and no cost savings.
606 (74%) of cases were net cost savers compared to their controls (cost difference <0). High cost savers (n=121) saved on average $10,690 compared to their matched controls. They were statistically more likely to have been diagnosed with bipolar disorder (n=33/121) than low cost savers (n=57/485) or non-savers (n=31/211), and had a lower Charlson Comorbidity index. High cost savers had fewer mean number of antidepressants in the baseline period (mean=3.16) compared to non-savers (3.73) but more than low cost savers (2.72) (p<0.05 across groups). In a multivariable model, bipolar, count of antidepressants, outpatient visits, and inpatient visits were statistically associated with being a high cost saver; antidepressant count and all-cause inpatient and outpatient visits in the baseline period were inversely associated with cost savings.
Use of a pharmacogenetic assay was associated with cost-savings in the database of a large commercial insurer. Patients with bipolar disorder were more likely to be high cost savers than individuals with other mood and anxiety disorders.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
The 21st Century Cures Act (“Cures Act”) relies on the concept of real-world evidence (“RWE”) to improve the Food and Drug Administration (“FDA”) approval process. This has amplified interest and furthered momentum in applying RWE more broadly, beyond FDA regulation. In this article, we discuss the understandable appeal of RWE's pragmatic application and its many potential benefits. But we also caution that claims about RWE's wide-ranging, ameliorative impact on the health care system are likely overstated.
The real world of RWE is messy and uncertain. Successfully incorporating RWE into regular health care system decision-making, beyond the FDA, faces considerable obstacles and limitations. We review the reasons to be wary about RWE as a game-changer. These concerns including data reliability, insufficient incentives for stakeholders to generate and engage with high-quality RWE, and lack of comprehensive regulatory oversight. In addition, the push for RWE may impact the enforcement of the health care fraud and abuse laws, perhaps not in necessarily positive ways. Increased reliance on RWE may have significant implications for off-label fraud enforcement, further conflating the distinction between claims that are false for reimbursement rather than for scientific purposes.
High concentrations of indium (In) and selenium (Se) have been reported in the Neves-Corvo volcanic-hosted massive sulfide deposit, Portugal. The distribution of these ore metals in the deposit is complex as a result of the combined effects of early ore-forming processes and late tectonometamorphic remobilization. The In and Se contents are higher in Cu-rich ore types, and lower in Zn-rich ore types. At the deposit scale, both In and Se correlate positively with Cu, whereas their correlations with Zn are close to zero. This argues for a genetic connection between Cu, In and Se in terms of metal sourcing and precipitation. However, re-distribution and re-concentration of In and Se associated with tectonometamorphic deformation are also processes of major importance for the actual distribution of these metals throughout the whole deposit. Although minor roquesite and other In-bearing phases were recognized, it is clear that most In within the deposit is found incorporated within sphalerite and chalcopyrite. When chalcopyrite and sphalerite coexist, the In content in sphalerite (avg. 1400 ppm) is, on average, 2–3 times higher than in chalcopyrite (avg. 660 ppm). The In content in stannite (avg. 1.3 wt.%) is even higher than in sphalerite, but the overall abundance of stannite is subordinate to either sphalerite or chalcopyrite. Selenium is dispersed widely between many different ore minerals, but galena is the main Se-carrier. On average, the Se content in galena is ~50 times greater than in either chalcopyrite (avg. 610 ppm) or sphalerite (avg. 590 ppm). The copper concentrate produced at Neves-Corvo contains very significant In (+Se) content, well above economic values if the copper smelters recovered it. Moreover, the high In content of sphalerite from some Cu-Zn ores, or associated with shear structures, could possibly justify, in the future, a selective exploitation strategy for the production of an In-rich zinc concentrate.
In this essay, we discuss the under-representation of women in leadership positions in global health (GH) and the importance of mentorship to advance women's standing in the field. We then describe the mentorship model of GROW, Global Research for Women. We describe the theoretical origins of the model and an adapted theory of change explaining how the GROW model for mentorship advances women's careers in GH. We present testimonials from a range of mentees who participated in a pilot of the GROW model since 2015. These mentees describe the capability-enhancing benefits of their mentorship experience with GROW. Thus, preliminary findings suggest that the GROW mentorship model is a promising strategy to build women's leadership in GH. We discuss supplemental strategies under consideration and next steps to assess the impact of GROW, providing the evidence to inform best practices for curricula elsewhere to build women's leadership in GH.
Impulsivity is a core feature of borderline personality disorder (BPD) and attention deficit hyperactivity disorder (ADHD). In BPD, impulsive behavior primarily occurs under acute stress; impulse control deficits under non-stress conditions may be partly related to co-morbid ADHD. We aimed to investigate whether acute experimental stress has an impact on self-reported impulsivity, response inhibition (action withholding, action cancelation) and delay discounting in BPD compared to ADHD.
Thirty female BPD patients, 28 female ADHD patients (excluding patients with co-morbid BPD and ADHD), and 30 female healthy controls (HC) completed self-reports and behavioral measures of impulsivity (IMT, assessing action withholding; GoStop, measuring action cancelation, Delay Discounting Task) under baseline conditions and after an experimental stress induction (Mannheim Multicomponent Stress Test).
Both patient groups reported higher impulsivity than HC, ADHD reported higher trait impulsivity than BPD. On the IMT, ADHD showed significant action-withholding deficits under both conditions, while BPD performed significantly worse than HC under stress. In BPD but not ADHD and HC, action-withholding deficits (IMT) were significantly increased under stress compared to baseline, while no group/stress effects were found for action cancelation (GoStop). Delay discounting was significantly more pronounced in BPD than in HC (no stress effect was found).
In BPD, behavioral deficits in action withholding (but not in action cancelation) appear to be influenced by acute experimental stress. Delay discounting seems to be a general feature of BPD, independent of co-morbid ADHD and acute stress, possibly underlying typical expressions of behavioral impulsivity in the disorder.
Previous research on impulsivity in borderline personality disorder (BPD) has revealed inconsistent findings. Impulsive behaviour is often observed during states of emotional distress and might be exaggerated by current attention deficit hyperactivity disorder (ADHD) symptoms in individuals with BPD. We aimed to investigate different components of impulsivity dependent on stress induction controlling for self-reported ADHD symptoms in BPD.
A total of 31 unmedicated women with BPD and 30 healthy women (healthy controls; HCs), matched for age, education and intelligence, completed self-reports and behavioural tasks measuring response inhibition (go/stop task) and feedback-driven decision making (Iowa Gambling Task) under resting conditions and after experimental stress induction. ADHD symptoms were included as a covariate in the analyses of behavioural impulsivity. Additionally, self-reported emotion-regulation capacities were assessed.
BPD patients reported higher impulsive traits than HCs. During stress conditions – compared with resting conditions – self-reported impulsivity was elevated in both groups. Patients with BPD reported higher state impulsivity under both conditions and a significantly stronger stress-dependent increase in state impulsivity. On the behavioural level, BPD patients showed significantly impaired performance on the go/stop task under stress conditions, even when considering ADHD symptoms as a covariate, but not under resting conditions. No group differences on the Iowa Gambling Task were observed. Correlations between impulsivity measures and emotion-regulation capacities were observed in BPD patients.
Findings suggest a significant impact of stress on self-perceived state impulsivity and on response disinhibition (even when considering current ADHD symptoms) in females with BPD.
To evaluate the potential of using surficial shell accumulations for paleoenvironmental studies, an extensive time series of individually dated specimens of the marine infaunal bivalve mollusk Semele casali was assembled using amino acid racemization (AAR) ratios (n = 270) calibrated against radiocarbon ages (n = 32). The shells were collected from surface sediments at multiple sites across a sediment-starved shelf in the shallow sub-tropical São Paulo Bight (São Paulo State, Brazil). The resulting 14C-calibrated AAR time series, one of the largest AAR datasets compiled to date, ranges from modern to 10,307 cal yr BP, is right skewed, and represents a remarkably complete time series: the completeness of the Holocene record is 66% at 250-yr binning resolution and 81% at 500-yr binning resolution. Extensive time-averaging is observed for all sites across the sampled bathymetric range indicating long water depth-invariant survival of carbonate shells at the sediment surface with low net sedimentation rates. Benthic organisms collected from active depositional surfaces can provide multi-millennial time series of biomineral records and serve as a source of geochemical proxy data for reconstructing environmental and climatic trends throughout the Holocene at centennial resolution. Surface sediments can contain time-rich shell accumulations that record the entire Holocene, not just the present.
Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD.
Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions.
Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus.
Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.
Setting priorities in the field of infectious diseases requires evidence-based and robust baseline estimates of disease burden. Therefore, the European Centre for Disease Prevention and Control initiated the Burden of Communicable Diseases in Europe (BCoDE) project. The project uses an incidence- and pathogen-based approach to measure the impact of both acute illness and sequelae of infectious diseases expressed in disability-adjusted life years (DALYs). This study presents first estimates of disease burden for four pathogens in Germany. The number of reported incident cases adjusted for underestimation served as model input. For the study period 2005–2007, the average disease burden was estimated at 33 116 DALYs/year for influenza virus, 19 115 DALYs/year for Salmonella spp., 8708 DALYs/year for hepatitis B virus and 740 DALYs/year for measles virus. This methodology highlights the importance of sequelae, particularly for hepatitis B and salmonellosis, because if omitted, the burden would have been underestimated by 98% and 56%, respectively.
Influenza surveillance in Danish intensive care units (ICUs) was performed during the 2009/10 and 2010/11 influenza seasons to monitor the burden on ICUs. All 44 Danish ICUs reported aggregate data for incidence and point prevalence, and case-based demographical and clinical parameters. Additional data on microbiological testing, vaccination and death were obtained from national registers. Ninety-six patients with influenza A(H1N1)pdm09 were recorded in 2009/10; 106 with influenza A and 42 with influenza B in 2010/11. The mean age of influenza A patients was higher in 2010/11 than in 2009/10, 53 vs. 44 years (P = 0·004). No differences in other demographic and clinical parameters were detected between influenza A and B patients. In conclusion, the number of patients with severe influenza was higher in Denmark during the 2010/11 than the 2009/10 season with a shift towards older age groups in influenza A patients. Influenza B caused severe illness and needs consideration in clinical and public health policy.
In view of the complexity of thin-film solar cells, which are comprised of a multitude of layers, interfaces, surfaces, elements, impurities, etc., it is crucial to characterize and understand the chemical and electronic structure of these components. Because of the high complexity of the Cu2ZnSn(S,Se)4 compound semiconductor absorber material alone, this is particularly true for kesterite-based devices. Hence, this paper reviews our recent progress in the characterization of Cu2ZnSnS4 (CZTS) thin films. It is demonstrated that a combination of different soft x-ray spectroscopies is an extraordinarily powerful method for illuminating the chemical and electronic material characteristics from many different perspectives, ultimately resulting in a comprehensive picture of these properties. The focus of the article will be on secondary impurity phases, electronic structure, native oxidation, and the CZTS surface composition.
This paper describes a semi-automated conductive ink process used for packaging MEMS devices. The method is applied to packaging of MEMS sensors for wind tunnel testing. The primary advantage of the method is a reduction in surface topology between the package and the integrated MEMS sensors. In this paper we explore the relationship between trace dimensions, resistivity, and deposition parameters such as feed rate, tip-substrate separation and tip diameter. Using this procedure it is possible to generate interconnects between a PC board and MEMS sensor chip with a topology of less than 25 micrometers.