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The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS on mood.
The aim of this study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).
44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”.
We found a significant reduction of the BDI score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI score were caused by sham stimulation (GLM, p = 0.109). We did not find significant differences caused by active or sham stimulation in VAS scales except for the VAS labelled lively/gloomy immediately after stimulation. The active group was found to be more “gloomy” (p = 0.001).
Our data support the hypothesis that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men.
Functional Transcranial Doppler sonography (fTCD) has been applied to assess peak mean cerebral blood flow velocity (MFV) with a high temporal resolution during cognitive activation. Yet, little attention has been devoted to gender-related alterations of MFV, including spectral analysis. In healthy subjects, fTCD was used to investigate a series of cerebral hemodynamic parameters in the middle cerebral arteries (MCA) during the Trail Making Tests (TMT), a means of selective attention and complex cognitive functioning. After the initial peak, there was an MFV decline during complex functioning. Further, in females, we observed a dynamic shift in hemispheric dominance during that condition and there was a frequency peak at 0.375 Hz in both MCA. These novel results suggest condition-specific features of cerebral hemodynamics in females, and it adds to the notion that gender is a fundamental confounder of brain physiology. It is intriguing to speculate whether condition-related alterations of spectral frequencies in females represent a marker of increased vulnerability for psychiatric diseases such as depression.
To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).
Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.
One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.
Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.
To study the efficacy and safety of phosphatidylserine (PS) containing Omega3 long-chain polyunsaturated fatty acids attached to its backbone (PS-Omega3) in reducing attention-deficit/ hyperactivity disorder (ADHD) symptoms in children.
A 15-week, double-blind, placebo-controlled phase followed by an open-label extension of additional 15 weeks. Two hundred ADHD children were randomized to receive either PS-Omega3 or placebo, out of them, 150 children continued into the extension. Efficacy was assessed using Conners’ parent and teacher rating scales (CRS-P,T), Strengths and Difficulties Questionnaire (SDQ), and Child Health Questionnaire (CHQ). Safety evaluation included adverse events monitoring.
The key finding of the double-blind phase was the significant reduction in the Global:Restless/impulsive subscale of CRS-P and the significant improvement in Parent impact-emotional (PE) subscale of the CHQ, both in the PS-Omega3 group. Exploratory subgroup analysis of children with a more pronounced hyperactive/impulsive behavior, as well as mood and behavior-dysregulation, revealed a significant reduction in the ADHD-Index and hyperactive components. Data from the open-label extension indicated sustained efficacy for children who continued to receive PS-Omega3. Children that switched to PS-Omega3 treatment from placebo showed a significant reduction in subscales scores of both CRS-P and the CRS-T, as compare to baseline scores. The treatment was well tolerated.
The results of this 30-week study suggest that PS-Omega3 may reduce ADHD symptoms in children. Preliminary analysis suggests that this treatment may be especially effective in a subgroup of hyperactive-impulsive, emotionally and behaviorally-dysregulated ADHD children.
Very-large-scale motions (VLSMs) and large-scale motions (LSMs) coexist at moderate Reynolds numbers in a very long open channel flow. Direct numerical simulations two-way coupled with inertial particles are analysed using spectral information to investigate the modulation of VLSMs. In the wall-normal direction, particle distributions (mean/preferential concentration) exhibit two distinct behaviours in the inner flow and outer flow, corresponding to two highly anisotropic turbulent structures, LSMs and VLSMs. This results in particle inertia’s non-monotonic effects on the VLSMs: low inertia (based on the inner scale) and high inertia (based on the outer scale) both strengthen the VLSMs, whereas moderate and very high inertia have little influence. Through conditional tests, low- and high-inertia particles enhance VLSMs following two distinct routes. Low-inertia particles promote VLSMs indirectly through the enhancement of the regeneration cycle (the self-sustaining mechanism of LSMs) in the inner region, whereas high-inertia particles enhance the VLSM directly through contribution to the Reynolds shear stress at similar temporal scales in the outer region. This understanding also provides more general insight into inner–outer interaction in high-Reynolds-number, wall-bounded flows.
Two-way coupled direct numerical simulations are used to investigate the effects of inertial particles on self-sustained, turbulent coherent structures (i.e. the so-called regeneration cycle) in plane Couette flow at low Reynolds number just above the onset of transition. Tests show two limiting behaviours with increasing particle inertia, similar to the results from previous linear stability analyses: low-inertia particles trigger the laminar-to-turbulent instability whereas high-inertia particles tend to stabilize turbulence due to the extra dissipation induced by particle–fluid coupling. Furthermore, it is found that the streamwise coupling between phases is the dominant factor in damping of the turbulence and is highly related to the spatial distribution of the particles. The presence of particles in different turbulent coherent structures (large-scale vortices or large-scale streaks) determines the turbulent kinetic energy of particulate phase, which is related to the particle response time scaled by the turnover time of large-scale vortices. By quantitatively investigating the periodic character of the whole regeneration cycle and the phase difference between linked sub-steps, we show that the presence of inertial particles does not alter the periodic nature of the cycle or the relative length of each of the sub-steps. Instead, high-inertia particles greatly weaken the large-scale vortices as well as the streamwise vorticity stretching and lift-up effects, thereby suppressing the fluctuating amplitude of the large-scale streaks. The primary influence of low-inertia particles, however, is to strengthen the large-scale vortices, which fosters the cycle and ultimately reduces the critical Reynolds number.
The building blocks of planets in planet-forming (“protoplanetary”) disks are assembled early in the lifetime of a young star. The gas disks are relatively short-lived, with a half-life of about 3 million years, as chemical reactions modify the reservoir of material from the natal molecular cloud. Spitzer Space Telescope Infrared Spectrograph (IRS) spectra of protoplanetary disks around T Tauri stars show emission from H2O and absorption from other gases, sometimes consistent with formaldehyde, H2CO , and other times consistent with formic acid, HCOOH, in the 5-7.5 μm region. SOFIA-EXES spectra of YSOs that follow up on these Spitzer-IRS studies are presented. How the gaseous features observed between 5-7.5 μm relate to those at other wavelengths is discussed. This work suggests that water and organic molecules, which are crucial for life as we know it, are present in the habitable zones of stars at a very early age [of 1-3 million years].
Using kerf-free wafering technologies material losses in semiconductor manufacturing processes can be reduced drastically. By the use of externally applied stress, crystalline materials can be separated along crystal planes with clearly defined thickness. Nevertheless, during this process striations caused by the crack propagation occur. These crack growth features are river and Wallner lines. In this work, we demonstrate a process for spalling that scales favorably for large-area semiconductor substrates with a diameter up to 300 mm. To get rid of the crack growth features, a laser-conditioning process with a high numerical aperture at photon energies below the material bandgap energy, using multi-photon effects is utilized. The process affords a surface roughness Ra after spalling of <1 µm.
People with severe mental illness (SMI) have a high risk of living socially excluded from the mainstream society. Policy initiatives and health systems aim to improve the social situation of people who suffer from mental health disabilities. The aim of this study was to explore the extent of social exclusion (employment and income, social network and social activities, health problems) of people with SMI in Switzerland.
Data from the Swiss Health Survey 2012 were used to compare the social exclusion magnitude of people with SMI with those suffering from severe physical illness, common mental illness and the general population.
With the exception of Instrumental Activities of Daily Living, we found a gradient of social exclusion that showed people with SMI to be more excluded than the comparison groups. Loneliness and poverty were widespread among people with SMI. Logistic regression analyses on each individual exclusion indicator revealed that people with SMI and people with severe physical illness were similarly excluded on many indicators, whereas people with common mental illness and the general population were much more socially included.
In contrast to political and health system goals, many people with SMI suffer from social exclusion. Social policy and clinical support should increase the efforts to counter exclusionary trends, especially in terms of loneliness and poverty.
Older people have a higher risk of drug-related problems (DRPs). However, little is known about the prevalence of DRPs in community-dwelling people who screened positive for dementia. Our study aimed to determine (1) the prevalence and types of DRPs and (2) the socio-demographic and clinical variables associated with DRPs in people screened positive for dementia in primary care.
The Dementia: life- and person-centered help in Mecklenburg-Western Pomerania (DelpHi-MV) study is a general practitioner (GP)-based cluster-randomized controlled intervention study to implement and evaluate an innovative concept of collaborative dementia care management in the primary care setting in Germany. Medication reviews of 446 study participants were conducted by pharmacists based on a comprehensive baseline assessment that included a computer-based home medication assessment. ClinicalTrials.gov Identifier: NCT01401582.
A total of 1,077 DRPs were documented. In 414 study participants (93%), at least one DRP was detected by a pharmacist. The most frequent DRPs were administration and compliance problems (60%), drug interactions (17%), and problems with inappropriate drug choice (15%). The number of DRPs was significantly associated with the total number of drugs taken and with a formal diagnosis of a mental or behavioral disorder.
Degree of cognitive impairment (MMSE defined) and formal diagnosis of dementia were not risk factors for an increased number of DRPs. However, the total number of drug taken and the presence of a diagnosis of mental and behavioral disorders were associated with an increased total number of DRPs.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
We present the preliminary results from observing the nearby radio galaxy M 87 for 156 hours (between the years 2012 and 2015) with the MAGIC telescopes, which lead to a significant very high energy (VHE, E > 100 GeV) detection of the source in quiescent states each year. Our VHE analysis combined with quasi-simultaneous data at other energies (from gamma-rays, X-rays, optical and radio) provides a unique opportunity to study the source variability and its broadband spectral energy distribution, which is found to disfavour a one-zone synchrotron/synchrotron self-Compton model. Therefore, other alternative scenarios for the photon emission are explored. We also find that the VHE emission is compatible with being produced close to the source radio core as previous data already indicated. A detailed paper presenting full results of the observing campaign is in preparation.
Control of fire was a hallmark of developing human cognition and an essential technology for the colonisation of cooler latitudes. In Europe, the earliest evidence comes from recent work at the site of Cueva Negra del Estrecho del Río Quípar in south-eastern Spain. Charred and calcined bone and thermally altered chert were recovered from a deep, 0.8-million-year-old sedimentary deposit. A combination of analyses indicated that these had been heated to 400–600°C, compatible with burning. Inspection of the sediment and hydroxyapatite also suggests combustion and degradation of the bone. The results provide new insight into Early Palaeolithic use of fire and its significance for human evolution.
Protein fermentation end products may damage the colonic mucosa, which could be counteracted by dietary inclusion of fermentable carbohydrates (fCHO). Although fermentable crude protein (fCP) and fCHO are known to affect microbial ecology, their interactive effects on epithelial barrier function are unknown. In the present study, in a 2 × 2 factorial experiment, thirty-two weaned piglets were fed low-fCP/low-fCHO (14·5 % crude protein (CP)/14·5 % total dietary fibre (TDF)), low-fCP/high-fCHO (14·8 % CP/16·6 % TDF), high-fCP/low-fCHO (19·8 % CP/14·5 % TDF) and high-fCP/high-fCHO (20·1 % CP/18·0 % TDF) diets. After 21–23 d, samples of proximal and distal colonic mucosae were investigated in Ussing chambers with respect to the paracellular and transcytotic passages of macromolecules and epithelial ion transport. The high-fCHO diets were found to reduce the permeability of the distal colon to the transcytotic marker horseradish peroxidase (HRP, 44 kDa; P <0·05) and also reduce the paracellular permeation of N-hydroxysuccinimide-biotin into the submucosa (443 Da; P <0·05), whereas that of HRP was decreased by the high-fCP diets (P <0·01). Short-circuit current (active ion transport), transepithelial resistance (barrier function) and charge selectivity were largely unaffected in both the segments. However, the high-fCP diets were found to suppress the aldosterone-induced epithelial Na channel activity (P <0·01) irrespective of fCHO inclusion. The high-fCP diets generally reduced the expression of colonic claudin-1, claudin-2 and claudin-3 (P <0·01), while that of claudin-4 was increased by the high-fCHO diets (P <0·01). The high-fCHO diets also altered the ratio between occludin forms (P <0·05) and increased the expression of tricellulin in the proximal colon, which was not observed with high-fCP diets. In conclusion, dietary fCHO and fCP exerted few and largely independent effects on functional measurements, but altered tight junction protein composition in a compensatory way, so that colonic transport and barrier properties were only marginally affected.
The aim of this study was to investigate the epidemiology of influenza A virus infection in Cyprus from the 2009 pandemic until 2013. Pandemic influenza A(H1N1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. The pandemic virus was also the prevalent influenza strain during influenza season 2010–2011; however, it was completely replaced by H3N2 subtype in the next season. During the most recent influenza season, 2012–2013, the pandemic strain was once again the only influenza A virus circulating in Cyprus. Full-length neuraminidase gene sequencing revealed mutations that had previously been identified as permissive. No significant difference in the expression of the IFN-inducible genes OAS and IFIT1 were observed. The phylogenetic analysis of the neuraminidase gene sequences revealed a picture of continuous importation of influenza strains in the island of Cyprus with local circulation playing only a minor role in determining the prevalent strain of the next influenza season.
The complex admittance of the Si+/SiO2/Pentacene/Au (metal/oxide/pentacene) thin film junctions is investigated under ambient conditions. The results are compared with the ones obtained for the corresponding Si+/SiO2/Au junctions (i.e. a small part of the surface left free from pentacene) which constitutes the “reference” of our samples. This allows us to extract the “organic” part of the dielectric response from the whole spectrum. Our data clearly show that the admittance is decomposed in three main contributions. At low frequencies, a contribution attributed to proton diffusion through the oxide is seen. This diffusion is shown to be anomalous and is believed to be also at the origin of the bias stress effect observed in organic field effect transistors. At higher frequencies, two dipolar contributions are evidenced, attributed to defects located one at the organic/oxide interface or within the organic, and the other in the bulk of the oxide. These two dipolar responses show different dynamic properties that manifest themselves in the admittance in the form of a Debye contribution for the defects located in the oxide, and of a Cole-Cole contribution for the defects related to the organic.
Wetlands are a key archive for paleoclimatic and archeological work, particularly in arid regions, as they provide a focus for human occupation and preserve environmental information. The sedimentary record from 'Ayn Qasiyya, a spring site on the edge of the Azraq Qa, provides a well-dated sequence through the last glacial–interglacial transition (LGIT) allowing environmental changes in the present-day Jordanian desert to be investigated robustly through this time period for the first time. Results show that the wettest period at the site preceded the last glacial maximum, which itself was characterised by marsh formation and a significant Early Epipaleolithic occupation. A sedimentary hiatus between 16 and 10.5 ka suggests a period of drought in the region although seasonal rains and surface waters still allowed seasonal occupation of the Azraq region. Archeological evidence suggests that conditions had improved by the Late Epipaleolithic, about the time of the North Atlantic Younger Dryas. The changes between wet and dry conditions at the site show similarities to patterns in the eastern Mediterranean and in Arabia suggesting the Jordan interior was influenced by changes in both these regions through the LGIT climatic transition.