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Mental health service delivery in the general health care sector is restricted with regard to understanding the magnitude and impact of mental illness in the medically ill (co-morbidity), as well as the significance of current mental health service delivery. A new model in development in the framework of a Biomed2 grant is presented. It consists of case-finding through complexity of hospital care prediction (COMPRI) followed by an integral health service needs assessment (INTERMED). It might serve to develop a more structural relation with the general health care sector for the management of mentally co-morbid high utilizing patients.
The orexins (hypocretins) are neuropeptides recently identified as neurotransmitters in lateral hypothalamus neurons. Although the majority of studies associated the function of orexin neurons with arousal and sleep, these neurons also project to reward-associated brain regions, including the nucleus accumbens and ventral tegmental area. This indicates a possible role for orexins in reward function and motivation and thus in addictive diseases. Additionally, there is growing evidence from preclinical studies for an involvement of orexins in the regulation of stress, affectivity and drug seeking behavior.
We investigated orexin plasma concentrations and psychological symptoms in a sample of 34 alcohol dependent subjects on day 1 and day 14 of detoxification. For this purpose we used the Brief Symptom Inventory (BSI) as well as the Obsessive-Compulsive Drinking Scale to identify self-reported clinically relevant psychological symptoms including alcohol craving.
As a main result a significant positive correlation between orexin plasma concentration and depression as well as global distress indicies of the BSI was detected during early withdrawal (day 1), which is not shown after detoxification on day 14. No association with subjective craving for alcohol was found.
Our data indicate that orexins may be directly involved in affective dysregulation in alcohol dependent patients; moreover the effects of orexins on reinstatement of drug seeking behaviors might be mediated by impaired brain stress systems.
To assess the prevalence of prediabetes and metabolic abnormalities among overweight or obese clozapine- or olanzapine-treated schizophrenia patients, and to identify characteristics of the schizophrenia group with prediabetes.
A cross-sectional study assessing the presence of prediabetes and metabolic abnormalities in schizophrenia clozapine- or olanzapine-treated patients with a body mass index (BMI) ≥27 kg/m2. Procedures were part of the screening process for a randomized, placebo-controlled trial evaluating liraglutide vs placebo for improving glucose tolerance. For comparison, an age-, sex-, and BMI-matched healthy control group without psychiatric illness and prediabetes was included. Prediabetes was defined as elevated fasting plasma glucose and/or impaired glucose tolerance and/or elevated glycated hemoglobin A1c.
Among 145 schizophrenia patients (age = 42.1 years; males = 59.3%) on clozapine or olanzapine (clozapine/olanzapine/both: 73.8%/24.1%/2.1%), prediabetes was present in 69.7% (101 out of 145). While schizophrenia patients with and without prediabetes did not differ regarding demographic, illness, or antipsychotic treatment variables, metabolic abnormalities (waist circumference: 116.7±13.7 vs 110.1±13.6 cm, P = 0.007; triglycerides: 2.3±1.4 vs 1.6±0.9 mmol/L, P = 0.0004) and metabolic syndrome (76.2% vs 40.9%, P<0.0001) were significantly more pronounced in schizophrenia patients with vs without prediabetes. The age-, sex-, and BMI-matched healthy controls had significantly better glucose tolerance compared to both groups of patients with schizophrenia. The healthy controls also had higher levels of high-density lipoprotein compared to patients with schizophrenia and prediabetes.
Prediabetes and metabolic abnormalities were highly prevalent among the clozapine- and olanzapine-treated patients with schizophrenia, putting these patients at great risk for later type 2 diabetes and cardiovascular disease. These results stress the importance of identifying and adequately treating prediabetes and metabolic abnormalities among clozapine- and olanzapine-treated patients with schizophrenia.
ESA's Gaia space astrometry mission is performing an all-sky survey of stellar objects. At the beginning of the nominal mission in July 2014, an operation scheme was adopted that enabled Gaia to routinely acquire observations of all stars brighter than the original limit of G~6, i.e. the naked-eye stars. We present the current status and extent of those observations.
Severe health anxiety is frequent and costly, yet rarely diagnosed or treated. Earlier treatment studies show problems with recruitment, dropout and recovery. In the current study, the authors aimed to test the effect of acceptance and commitment group therapy (ACT-G) compared to waitlist in patients with severe health anxiety.
During March 2010 to April 2012, 126 consecutively referred patients meeting research criteria for severe health anxiety were block-randomized (1:1) to ACT-G or a 10 months’ waitlist (Clinicaltrials.gov, no. NCT01158430). Patients allocated to ACT-G were treated in seven groups of nine patients between December 2010 and October 2012 and received nine weekly 3-h group sessions and a booster session consisting of ACT techniques. The primary outcome was decided a priori as the mean change in self-reported illness worry on the Whiteley-7 Index (WI) from baseline to 10 months’ follow-up. Secondary outcomes were improvement in emotional distress and health-related quality of life at 10 months’ follow-up.
Intention-to-treat analysis showed a statistically significant mean difference of 20.5 points [95% confidence interval (CI) 11.7–29·4, p < 0.001] on the WI between the groups at 10 months, and the between-group effect sizes were large (Cohen's d = 0.89, 95% CI 0.50–1.29). The number needed to treat was 2.4 (95% CI 1.4–3.4, p < 0.001). Diagnosis and treatment were well accepted by the patients.
ACT-G seems feasible, acceptable and effective in treating severe health anxiety.
Word-initial /s/-consonant clusters do not occur in Spanish. Confronted with such sequences (e.g., in loanwords), Spanish speakers tend to perceive an illusory initial /e/, ‘repairing’ the illicit sequence. In two experiments, both conducted in Spanish with Spanish-sounding nonwords, we ask whether knowledge of English, which has no restriction against this sound sequence, weakens this pattern of perceptual repair in fluent Spanish–English bilinguals, and whether the effects of English depend on language dominance. In both identification and discrimination tasks, bilinguals exhibited weaker perceptual repair effects relative to Spanish monolinguals. This was true even for bilinguals dominant in Spanish, though the weakening was more pronounced for English-dominant bilinguals. These results show that conflicting phonotactic systems can jointly influence bilinguals’ perceptual repair of the acoustic signal in the more restrictive language, even when it is the bilingual's dominant language, suggesting a degree of integration and mutual influence of knowledge between both their languages.
Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and expanded according to good manufacturing practice guidelines and a basic assurance of quality, safety, and medical effectiveness is needed for authorisation by regulatory agencies, such as European Medicines Agency and US Food and Drug Administration. In this review, a collection of studies investigating the influence of different steps of the isolation and expansion protocol on the yield and functionality of ASCs has been presented in an attempt to come up with best recommendations that ensure potential beneficial clinical outcome of using ASCs in any therapeutic setting. If the findings confirm the initial observations of beneficial effects of ASCs, the path is paved for implementing these ASC-based therapies as standard treatment options.
Here we report on the design, fabrication, and characterization of fiber containing an internal crystalline non-centrosymmetric phase enabling piezoelectric functionality over extended fiber lengths . A ferroelectric polymer layer of 30 μm thickness is spatially confined and electrically contacted by internal viscous electrodes and encapsulated in an insulating polymer cladding hundreds of microns in diameter. The structure is thermally drawn in its entirety from a macroscopic preform, yielding tens of meters of piezoelectric fiber. Electric fields in excess of 50V/μm are applied through the internal electrodes to the ferroelectric layer leading to effective poling of the structure. To unequivocally establish that the internal copolymer layer is macroscopically poled we adopt a two-step approach. First, we show that the internal piezoelectric modulation indeed translates to a motion of the fiber’s surface using a heterodyne optical vibrometer at kHz frequencies. Second, we proceed to an acoustic wave measurement at MHz frequencies: a water-immersion ultrasonic transducer is coupled to a fiber sample across a water tank, and frequency-domain characterizations are carried out using the fiber successively as an acoustic sensor and actuator. These measurements establish the broadband piezoelectric response and acoustic transduction capability of the fiber. The potential to modulate sophisticated optical devices is illustrated by constructing a single-fiber electricallydriven device containing a high-quality-factor Fabry-Perot optical resonator and a piezoelectric transducer.
Milk contains immunomodulatory compounds that may be important to protect the immature intestine in preterm neonates from harmful inflammatory reactions involved in disorders like necrotising enterocolitis (NEC). We hypothesised that bovine colostrum and milk formulas enriched with sialic acids (SL), gangliosides (Gang) or osteopontin (OPN) would improve gastrointestinal function and NEC resistance in preterm neonates. Forty-seven caesarean-delivered preterm pigs were given total parenteral nutrition for 2 d followed by 1·5 d of enteral feeding. In Expt 1, a control formula was compared with an OPN-enriched formula (n 13), while Expt 2 compared a control formula with bovine colostrum or formulas enriched with Gang or SL (n 4–6). OPN enrichment decreased NEC severity relative to control formula (P < 0·01), without any significant effects on NEC incidence, digestive enzyme activities and hexose absorption. Neither SL- nor Gang-enriched formulas improved NEC resistance or digestive functions, while all the intestinal functional parameters were significantly improved in pigs fed bovine colostrum, relative to formula. The effects in vivo were supported in vitro by bacteria- and dose-dependent modulation by colostrum whey of the cytokine response from bacteria-stimulated murine bone marrow-derived dendritic cells (DC). In conclusion, OPN had only moderate NEC-protective effects, while formulas enriched with Gang or SL were ineffective. The observed modulation of DC cytokine response by bovine colostrum whey in vitro may be due to a synergistic action of various milk bioactives, and it may explain its beneficial effects on NEC development and intestinal function in a piglet model of preterm infants.
George J. Brewer, Department of Human Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA,
Fred Askari, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA,
Matthew T. Lorincz, Department of Neurology, University of Michigan, Ann Arbor, MI, USA,
Martha Carlson, Department of Pediatrics-Neurology, University of Michigan, Ann Arbor, MI, USA,
Michael Schilsky, Department of Internal Medicine, Cornell University, New York, NY, USA,
Karen J. Kluin, Department of Neurology, Department of Speech Pathology, University of Michigan, Ann Arbor, MI, USA,
Peter Hedera, Department of Neurology, Vanderbilt University, Nashville, TN, USA,
Paolo Moretti, Departments of Neurology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA,
John K. Fink, Department of Neurology, University of Michigan, Ann Arbor, MI, USA,
Roberta Tankanow, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA,
Robert B. Dick, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA,
Julia Sitterly, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks. Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05).
Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeksThis study was originally published in reference 1. Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05). One patient on trientine had an adverse event while 7 on TM had adverse events. All adverse events were mild. Four patients in the trientine arm died during follow-up, 3 having shown initial neurologic deterioration, 2 patients in the TM arm died. In those patients who did not deteriorate or die, neurologic and speech recovery over 3 years was good. Interpretation: TM is a superior choice to trientine for the initial therapy of neurologic Wilson's disease.
This study compared the prevalence and intensity of infections of helminths in 2 chicken breeds in Vietnam, the indigenous Ri and the exotic Luong Phuong. Also, possible correlations with the Major Histocompatibility Complex (MHC) were tested. The most prevalent helminths were Ascaridia galli, Heterakis beramporia, Tetrameres mothedai, Capillaria obsignata, Raillietina echinobothrida and Raillietina tetragona. Differences in prevalence and intensity of infection were found between the 2 breeds. Comparing the 2 groups of adult birds, Ri chickens were observed to have higher prevalence and infection intensities of several species of helminths, as well as a higher mean number of helminth species. In contrast, A. galli and C. obsignata were shown to be more prevalent in Luong Phuong chickens. Furthermore, an age-dependent difference was indicated in the group of Ri chickens in which the prevalence and the intensity of infection was higher for the adult than the young chickens for most helminths. The most notable exception was the significantly lower prevalence and intensities of A. galli in the group of adult chickens. In contrast, the prevalence and intensity were very similar in both age groups of Luong Phuong chickens. Using a genetic marker located in the MHC, a statistically significant correlation between several MHC haplotypes and the infection intensity of different helminth species was inferred. This is the first report of an association of MHC haplotype with the intensity of parasite infections in chickens.
Previous research has suggested that offspring sex ratio may be influenced by the actions of prenatal sex steroids, principally androgens. The relative length of the second (index finger) to the fourth digit (ring finger) has been reported to be a proxy to prenatal testosterone levels. This trait is sexually dimorphic, such that males display a significantly lower 2D:4D ratio (indicating higher testosterone exposure), and this dimorphism appears robust across different populations. We suggest that digit ratio (2D:4D) may form a useful marker to help explain variation in sex ratio and sociosexuality.
Fullerite nanotubules of 100 nm to 2 μm radius, up to 200 nm wal thickness and 10 μm length were produced inside etched swift heavy ion tracks in a polymer, by letting fullerence precipitate from a concentrated C60 solution within the tracks. After contacting the tubules on both sides with silver paste, their resistivity was measured as a function of temperature. All of the 13 prepared samples show a complex behaviour that can be described by tw Arrhenius curves, the low temperature branch with activation energy Eact = (1.77 ± 0.2) eV stemming from pure C60, and the high temperature branch being tentatively ascribed to C60Agx with x ≍ 12.4 and Eact = (0.68 ± 0.2) eV, as the letter compound has found to be produced at ambient temperature by C60 / Ag thermal intermixture. Such samples with tw branches of negative temperature coefficients of resistance might be useful to construct advanced thermoresistors.
We present the results of tests measuring the life of carbon cold cathodes and determining what conditions limit the life of the cathode. Cathode life and stability are important for a broad range of applications, including displays, electron sources for satellite thrusters, x-ray tubes and microwave devices. Cathodes were tested in vacuum chambers using different gas environments as well as in sealed and gettered glass envelopes. We measured emission current half-lives of 10,000 - 20,000 hours or more in sealed display devices, depending on operating conditions. The presence of a significant oxygen or water partial pressure degrades the life of the cathode. After removing the gases the decay rate was restored to near the original value. A similar partial pressure of hydrogen gas has little or no effect on the life of the cathode. Initial results of operation in a xenon environment indicate carbon cold cathodes are much more robust compared to microtip cathodes. These results will be discussed with respect to the various applications considered for carbon cold cathodes.