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Identifying and quantifying sex differences and similarities has been a central research question and fascinated scientists for centuries. A large body of work has been accumulated on this topic; however, conclusions are often drawn as if they are applicable across cultures even though studies have predominantly relied on Western samples. This chapter reviews cross-cultural literature on several early childhood sex differences in domains of development that have caught attention in the literature recently: gender-typed play, gender identity, and gender expression. We also offer an overview of possible influences on sex differences, including evolutionary, biodevelopmental (genetics, sex hormones, and immune factors), and sociocultural mechanisms (socialization and macro-cultural factors). Given that a cross-cultural perspective has often been lacking in this literature, this chapter reviews research on early gender development in males and females from Western populations as well as the non-Western populations wherever possible to highlight important cultural (in)consistencies.
The dendrite morphologies of the cast nickel-based superalloy CMSX-4® (CMSX-4® is registered trademarks of the Cannon-Muskegon Corporation) and the austenitic stainless steel HP microalloy have been obtained via an automated serial-sectioning process which allows three-dimensional (3D) microstructural characterization. The dendrite arm spacing, volume fraction of segregation, and fraction of porosity have been determined. This technique not only increases the depth, scope, and level of detailed microstructural characterization but also delivers microstructural data for modeling and simulation.
Combinational creativity can play a significant role in supporting designers to produce creative ideas during the early stages of new product development. This paper explores conceptual distances in combinational creativity from computational perspectives. A study conducted indicates that different computational measurements show different conceptual distance results. However, the study suggests far-related ideas could lead to outcomes that are more creative than closely-related ones. This paper provides useful insights into exploring future computational design support tools.
OBJECTIVES/GOALS: Nicotinamide adenine dinucleotide (NAD) plays essential roles in energy metabolism and cell signaling pathways. NAD functions as a coenzyme by accepting electrons during glycolysis and the TCA cycle and subsequently donates them to complex I of the electron transport chain providing the driving force for ATP production. NAD also acts as a co-substrate for several classes of enzymes, including sirtuin deacetylases. Both NAD and the enzyme that is rate limiting for synthesis, Nicotinamide phosphoribosyltransferase (Nampt), are depleted in the failing heart, concurrent with hyperacetylation and mitochondrial dysfunction. Moreover, treatment with NAD precursors reduced cardiac injury in several heart failure models. However, NAD precursors may have systemic effects, and it remains unproven whether depletion of myocardial NAD is causative or merely correlative for the onset and progression of heart failure. METHODS/STUDY POPULATION: To test this, we generated a cardiac-specific tamoxifen-inducible (αMHC-MerCreMer) model for deletion of Nampt (Nampt cKO) in cardiomyocytes. Adult mice were administered tamoxifen for 5 days leading to deletion of Nampt, resulting in a 72% reduction in myocardial NAD after two-weeks. RESULTS/ANTICIPATED RESULTS: Echocardiography revealed that Nampt cKO mice displayed a significant reduction in left ventricular (LV) contractility as well as cardiac hypertrophy. Despite the further loss of NAD, the majority of animals survived to 8 weeks of age before experiencing sudden deaths resulting in significant mortality over the next several weeks. Remarkably, we observed only a slight increase in acetylation of mitochondrial proteins, and cardiac mitochondria isolated from Nampt-null mice even at 8 weeks displayed a normal or higher oxygen consumption rate. We found that mitochondrial NAD levels were preferentially maintained and depleted at a slower rate compared to those in bulk tissue. DISCUSSION/SIGNIFICANCE OF IMPACT: While mild depletion of cardiac NAD has been reported in heart failure, our data indicate that the heart can adapt to much more severe loss of NAD prior to the loss of viability.
Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.
The extra pyramidal effects related to the use of neuroleptics are a limiting factor in schizophrenia treatment.
The aim of this study was to identify the neuroleptics prescribed for schizophrenic patients in a public health service, the extra pyramidal symptoms (EPS) incidence and its treatment.
Our restrospective study included 40 patients with mean age of 39.13 ± 2.19 in a treatment period of of 134.17 ± 16.83 days. The data were randomly collected from medical records of these patients.
The patients under study received typical neuroleptics (31.03%),atypical agents (37.93%) or association of both (31.03%). EPS was observed in 65.52% patients of which, 44.83% even though receiving biperiden 2mg, still have EPS. 20.69% were not receiving anticolinergic drug treatment for EPS, but promethazine or anticonvulsants. From the 34.48% who did not showed EPS, 20.69% had biperiden prescription and 13.79 % had been treated with olanzapine, clozapine or risperidone associated or not to clonazepam 2mg. Weigth gain of 5.20 ± 1.14 kg was observed in our total sample.
We suggest the use of EPS evaluation scale (Sympson - Angus or Barnes). 65.52 % of the patients under study had EPS and 20.69% of them had no prescription of central acting anticholinergic drug. 44.83% even though receiving biperiden 2mg, still have EPS.
The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.
Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + mood stabilizer or placebo + mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test).
127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively).
These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.
Indoleamine-2, 3-dioxygenase is responsible for tryptophan catabolism; IFN-β is a treatment for multiple sclerosis (MS) and it has been associated with depression. IDO activation might play a role in IFN-β induction of depressive symptoms. Depressive symptoms associated with MS illness and IFN-β treatment have been treated with pharmacological and non-pharmacological intervention.
Evaluation of the kynurenine pathway, IDO activation and neurotoxic agents, serum BDNF in MS patients during IFN-β intervention.
14 study subjects, aged 18-64 years with major depressive disorder and MS treated with IFN-β, before and after pharmacologic and non-pharmacologic intervention, and 34 age matched healthy controls were enrolled at the University of Rome "La Sapienza" and at the at the University of Antwerp. Depressed participants were randomized to sertraline-treatment or interpersonal psychodynamic psychotherapy.
There were significant improvements in both depression and anxiety symptoms with medication and psychotherapy groups, although the effect with sertraline was more robust. Sertraline treatment was associated with a decline in serotonin. In the psychotherapy group, a significant increase in 3-hydroxyanthranilic acid (HAA) was observed after 4 months treatment (p= .04) with a significant decrease in tryptophan levels at 6 weeks (p= .02) and a trend towards a significant decrease in BDNF after 6 wks (p=0.06), neither of which were seen in the medication condition.
The increase in HAA among the psychotherapy-treated patients raises the possibility of a neurodegenerative challenge for patients with multiple sclerosis during treatment with IFN-β which appeared to be prevented with pharmacological treatment.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
More than 80 % of patients experiencing their first depressive episode will have at least one new episode. Effective interventions to reduce the risk of relapse and recurrence are needed. Psychoeducation is a form of interactive education enhancing knowledge about patients’ illness, including its course, symptoms and treatment. Psychoeducational methods can also act as family intervention – already an evidence-based practice in schizophrenia and bipolar disorder. Only few studies have focused on the effect of psychoeducation, including family psychoeducation, in the prevention of new depressive episodes.
Purpose is to evaluate whether an intervention of psychoeducation for family members, compared to a control intervention, is effective in reducing the risk of new depressive episodes among patients that have achieved remission or partial remission of depressive symptoms after the acute phase of antidepressive treatment.
The project is based on a double-centre, randomized controlled trial where investigator and raters conducting psychometric assessments, will be blinded to treatment allocation. A total of 130 patients with unipolar depression in remission or partial remission will be included together with their closest relative. After baseline assessments, relatives will be randomized to either 4 sessions of a family psychoeducation program or 4 sessions in a social support group without any psychoeducational intervention. Patients will not participate in group sessions and they will continue their outpatient-treatment as usual.
Primary outcome is evaluated after 9 months and include rates of relapse as measured by HAM-D17 and rates of recurrence according to DMS-VI-R and HAM-D17.
Persistent gaming, despite acknowledgment of its negative consequences, is a major criterion for individuals with Internet gaming disorder (IGD). This study evaluated the adaptive decision-making, risky decision, and decision-making style of individuals with IGD.
We recruited 87 individuals with IGD and 87 without IGD (matched controls). All participants underwent an interview based on the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) diagnostic criteria for IGD and completed an adaptive decision-making task; the Preference for Intuition and Deliberation Scale, Chen Internet Addiction Scale, and Barratt Impulsivity Scale were also assessed on the basis of the information from the diagnostic interviews.
The results demonstrated that the participants in both groups tend to make more risky choices in advantage trials where their expected value (EV) was more favorable than those of the riskless choice. The tendency to make a risky choice in advantage trials was stronger among IGD group than that among controls. Participants of both groups made more risky choices in the loss domain, a risky option to loss more versus sure loss option, than they did in the gain domain, a risky option to gain more versus sure gain. Furthermore, the participants with IGD made more risky choices in the gain domain than did the controls. Participants with IGD showed higher and lower preferences for intuitive and deliberative decision-making styles, respectively, than controls and their preferences for intuition and deliberation were positively and negatively associated with IGD severity, respectively.
These results suggested that individuals with IGD have elevated EV sensitivity for decision-making. However, they demonstrated risky preferences in the gain domain and preferred an intuitive rather than deliberative decision-making style. This might explain why they continue Internet gaming despite negative consequences. Thus, therapists should focus more on decision-making styles and promote deliberative thinking processes to mitigate the long-term negative consequences of IGD.
Involuntary hospitalization in those presumed to be mentally ill has been a common practice. Although some patients are hospitalized for aggression, two-thirds of the patients are hospitalized because of the threat they pose to themselves. Although these patients require risk assessment and evaluation for possible presence of mental illness, the question is how much these patients will benefit from involuntary admission and what the long-term outcome would be.
All patients admitted involuntary to the psychiatric ward in Kingston, Canada, and psychiatrists involved in their care were interviewed to see whether they think the involuntary admission was helpful. All patients were asked to fill-out MacArthur AES to assess their satisfaction with hospitalization.
Although psychiatrists frequently reported that the admission was justified, only 29 out of 81 patients reported being explained to why they had been admitted involuntarily. Also, there was a significant difference in AES scores between those who were and were not given an explanation for admission. In addition, psychiatrists more often reported that the involuntary admission worsened the therapeutic relationship which was significantly associated with involuntary admission that was not explained to patients.
The results of our study shows that patients admitted involuntarily often feel disappointed with staff and mental health system. It could lead to feeling of hopelessness, frustration and low self-esteem. If explained, some patients who present with risk to self might accept voluntary admissions, that will improve therapeutic alliance with psychiatrists and increase satisfaction from hospitalization. Result of this study could improve the decision making process for involuntary admissions.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals.
We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16–75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822.
There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25–3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI −0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42–2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function.
CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.
Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.
This study aimed at comparing the factors associated with the natural progression between typical progressors (TPs) and rapid progressors (RPs) in HIV-infected individuals. A retrospective study was conducted on 2095 eligible HIV-infected individuals from 1995 to 2016 in a high-risk area of Henan Province, China. Propensity score matching was used to balance covariates, and the conditional logistic regression analyses were performed to explore the factors of natural disease progression among HIV infectors. A total of 379 pairs of RPs and TPs were matched. The standardised difference values of all covariates were less than 10%. HIV-infected individuals transmitted through sexual transmission (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.36–0.85) were more likely to progress to AIDS compared with those infected through contaminated blood. Older age at diagnosis of HIV-infected individuals (OR 0.72, 95% CI 0.58–0.89) exhibited a faster progression to AIDS. HIV-infected individuals identified through a unique survey (OR 7.01, 95% CI 2.99–16.44) were less likely to progress to AIDS compared with those identified through medical institutions. HIV-infected individuals who had higher baseline CD4+T cell counts (OR 3.37, 95% CI 2.59–4.38) had a slower progression to AIDS. These findings provide evidence for natural disease progression from HIV to AIDS between TPs and RPs.
We formulate a model for the dynamic growth of a membrane developing in a flow as the result of a precipitation reaction, a situation inspired by recent microfluidic experiments. The precipitating solid introduces additional forces on the fluid and eventually forms a membrane that is fixed in the flow due to adhesion with a substrate. A key challenge is that, in general, the location of the immobile membrane is unknown a priori. To model this situation, we use a multiphase framework with fluid and membrane phases; the aqueous chemicals exist as scalar fields that react within the fluid to induce phase change. To verify that the model exhibits desired fluid–structure behaviours, we make simplifying assumptions to obtain a reduced form of the equations that is amenable to exact solution. This analysis demonstrates no-slip behaviour on the developing membrane without requiring fluid–membrane interface boundary conditions. The model has applications towards precipitate reactions where the precipitate greatly affects the surrounding flow, a situation appearing in many laboratory and geophysical contexts including the hydrothermal vent theory for the origin of life. More generally, this model can be used to address fluid–structure interaction problems that feature the dynamic generation of structures.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.