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Tooth enamel, the outermost layer of human teeth, is a complex, hierarchically structured biocomposite. The details of this structure are important in multiple human health contexts, from understanding the progression of dental caries (tooth decay) to understanding the process of amelogenesis and related developmental defects. Enamel is composed primarily of long, nanoscale crystallites of hydroxyapatite that are bundled by the thousands to form micron-scale rods. Studies with transmission electron microscopy show the relationships between small groups of crystallites and X-ray diffraction characterize averages over many rods, but the direct measurement of variations in local crystallographic structure across and between enamel rods has been missing. Here, we describe a synchrotron X-ray-based experimental approach and a novel analysis method developed to address this gap in knowledge. A ~500-nm-wide beam of monochromatic X-rays in conjunction with a sample section only 1 μm in thickness enables 2D diffraction patterns to be collected from small well-separated volumes within the enamel microstructure but still probes enough crystallites (~300 per pattern) to extract population-level statistics on crystallographic features like lattice parameter, crystallite size, and orientation distributions. Furthermore, the development of a quantitative metric to characterize relative order and disorder based on the azimuthal autocorrelation of diffracted intensity enables these crystallographic measurements to be correlated with their location within the enamel microstructure (e.g., between rod and interrod regions). These methods represent a step forward in the characterization of human enamel and will elucidate the variation of the crystallographic structure across and between enamel rods for the first time.
We investigate the phased evolution and variation of the South Asian monsoon and resulting weathering intensity and physical erosion in the Himalaya–Karakoram Mountains since late Pliocene time (c. 3.4 Ma) using a comprehensive approach. Neodymium and strontium isotopic compositions and single-grain zircon U–Pb age spectra reveal the sources of the deposits in the east Arabian Sea, and show a combination of sources from the Himalaya and the Karakoram–Kohistan–Ladakh Mountains, with sediments from the Indian Peninsula such as the Deccan Traps or Craton. We interpret shifts in the sediment sources to have been forced by sea-level changes that correlate with South Asian monsoon rainfall variation since late Pliocene time. We collected 908 samples from the International Ocean Discovery Program Hole U1456A, which was drilled in the east Arabian Sea. Time series of hematite content and grain size of the sediments were examined downcore. We found South Asian monsoon precipitation and weathering intensity experienced three phases from late Pliocene time. Lower monsoon precipitation, with a lower variability and strong weathering intensity, occurred during 3.4–2.4 Ma; an increased and more variable South Asian monsoon rainfall, along with strengthened but fluctuating weathering intensity, occurred at 1.8–1.1 Ma; and a reduced rainfall with lower South Asian monsoon precipitation variability and moderate weathering intensity marked the period 1.1–0.1 Ma. Maximum entropy spectral analysis and wavelet transform show that there were orbital-dominated cycles of periods c. 100 and c. 41 ka in these proxy-based time series. We propose that the monsoon, sea level, global temperature and insolation together forced the weathering and erosion in SW Asia.
Many studies showed the differences in subjective response to sexual stimuli between heterosexual and homosexual men. However, the underlying neurobiological factors of sexual orientation are largely unknown. We addressed the question what is the major attribution of the expected differences in brain activation, i.e. neural circuits or different cognitive process. Twenty-eight healthy male volunteers, 14 heterosexuals and 14 homosexuals, were scanned by functional Magnetic Resonance Imaging while subjects were viewing different types of stimuli, i.e. heterosexual couple stimuli (HCS), gay couple stimuli (GCS), lesbian couple stimuli (LCS) and neutral stimuli (NS). SPM02 was used for data analysis. Rating of sexual attractiveness was assessed. Subjective sexual arousal was induced by HCS and GCS in heterosexual and homosexual men, respectively. And sexual disgust was induced by GCS and LCS in heterosexual and homosexual men, respectively. As compared to viewing NS, viewing sexual stimuli induced significant different brain activations most of which had characteristic for cognitive process. These observations suggested that different cognitive pattern was major attribution of different subjective response to sexual stimuli between heterosexual and homosexual men.
To investigate the effect of Chinese herb Danshen-Dahuang on learning and memory ability in rats with Alzheimer disease (AD) induced by D-galactose and AlCl3 and its possible mechanisms.
The AD model was produced by injecting D-galactose and AlCl3 intraperitoneally for 90 days. Since the 20th day of D-galactose and AlCl3 intraperitoneal injection, the rats in Danshen-Dahuang group had been treated with Danshen-Dahuang extraction by intragastric administration for 70 days. Subsequently,learning and memory ability of the mice was evaluated by Morris water maze and hippocampal gene expression of APP, PS1 was tested by reverse transcription polymerase chain reaction (RT-PCR).
Rats intragastric administration with Danshen-Dahuang, mice had shorter latency (P< 0.05) and less error times (P< 0.05) in water maze test compared with those in AD model group. At the same time, Danshen-Dahuang down regulated the expression of APP, PS1 mRNA (P< 0.05) in hippocampus.
Danshen-Dahuang improves the learning and memory ability of AD rats, its mechanism may be related to the downregulated expression of APP, PS1 mRNA.
Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.
This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.
Recent imaging studies have shown that brain morphology and neural activity during sexual arousal differ between homosexual and heterosexual men. Whether the structural and task-related functional differences also exist in the resting state is unknown. The purpose of the study is to characterize the association of homosexual preference with measures of regional homogeneity and functional connectivity in the resting state. Participants were 26 homosexual men and 26 age-matched heterosexual men. The sexual orientation of every participant was evaluated using the Kinsey Scale. We first assessed group differences in regional homogeneity and then, taking the identified differences as seed regions, we compared groups in measures of functional connectivity from those seeds. The behavioral significances of the differences in regional homogeneity and functional connectivity were assessed by examining their associations with scores on the Kinsey Scale. Homosexual participants showed significantly reduced regional homogeneity in the left inferior occipital gyrus, right middle occipital gyrus, right superior occipital gyrus, left cuneus, right precuneus, and increased regional homogeneity in the rectal gyrus, bilateral midbrain, and left temporal lobe. Regional homogeneity correlated positively with Kinsey scores in the left inferior occipital gyrus. The homosexual group also showed reduced functional connectivity in left middle temporal gyrus, left supra-marginal gyrus and right cuneus. In addition, the connection between the left inferior occipital gyrus and right thalamus in the homosexual group was correlated positively with Kinsey scores. This differences in homogeneity and fucntional connectivity may contribute to a better understanding of the neural basis of male sexual orientation.
The main aim of the present studies is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorder in the depressed and clinically remitted status respectively.
Three groups of bipolar I (n = 92), bipolar II (n = 131) and unipolar depression patients (n = 293) were tested with a battery of neuropsychological tests at baseline and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance.
At the acute depressive state, the three patients groups (bipolar I, bipolar II and unipolar depression) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not attention compared with controls. And post comparisons revealed that bipolar I patients performed significantly worse in these impaired cognitive domain than bipolar II and unipolar depression patients in verbal fluency and executive function. After treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory in relative to controls, while remitted unipolar depression patients showed cognitive impairment in executive function in addition to processing speed and visual memory.
Bipolar I, bipolar II and unipolar depression patients have a similar pattern of cognitive impairment during the state of acute depressive episodes. At the clinically remission, still both bipolar disorder and unipolar depression patients showed cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for unipolar depression
The main aim of this study is to investigate the capacity of a number of variables from four dimensions (clinical, psychosocial, cognitive and genetic domains) to predict the antidepressant treatment outcome, and combined the predictors in one integrate regression model with the aim to investigate which predictor contributed most.
In a semi-naturalistic prospective cohort study with a total of 241 fully assessed MDD patients, decrease in HAM-D scores from baseline to after 6 weeks of treatment was used to measure the antidepressant treatment outcome.
The clinical and psychosocial model (R2 = 0.451) showed that HAM-D scores at baseline and MMPI-2 scale paranoia was the best clinical and psychosocial predictor of treatment outcome respectively. The cognitive model (R2 = 0.502) revealed that combination of better performance on TMT-B test and worse performance on TOH and WAIS-R Digit Backward testes could predict decline in HAM-D scores. The genetics analysis only found median of percent improvement in HAM-D scores in G-allele of GR gene BclI polymorphism carriers (72.2%) was significant lower than that in non-G allele carriers (80.1%). The integrate model showed that three predictors, combination of HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, explained 57.1% of the variance.
Three markers, HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, might serve as predictor of antidepressant outcome in daily psychiatric practice.
Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.
The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.
CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.
The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.
Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.
A health coach-led smoking cessation program was implemented in a community of immigrant Chinese Americans. Follow-up was provided face-to-face or over-the-phone to provide support and address barriers. Free nicotine replacement treatment was provided for eligible participants.
The aim is to assess smoking cessation outcome by program components.
Quitting was defined as self-reported smoking abstention for at least 3 months. Factors contributing to successful cessation were evaluated using chi-squared tests and regression analysis. Participants were randomly surveyed to measure the helpfulness of and satisfaction with the program.
The program enrolled 184 participants from November 2015 to January 2017. Participants were mostly men (89%) with a mean age of 44. An intent-to-treat analysis found that 19% quit. Phone counseling had the same success as face-to-face counseling. Each additional session attended was associated with 2.1 times the odds of quitting, P < 0.001. Among the participants who quit, 70% reported the health coach was helpful in their cessation.
A health coach-led smoking cessation program that offered phone-based counseling was successful in reducing smoking. Future programs should consider using a health coach to reduce physician burden and phone-based counseling for difficult-to-access patients to increase program reach.
Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.
In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).
By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10−25) and a negative correlation between MDD and former smoking (rg = −0.298; p = 1.59 × 10−24). MR analysis suggested that genetic liability for depression increased smoking.
These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.
To evaluate the upper airway morphology changes associated with ageing in adult Chinese patients with obstructive sleep apnoea.
A total of 124 male patients diagnosed with obstructive sleep apnoea by overnight polysomnography, who underwent upper airway computed tomography, were enrolled. The linear dimensions, cross-sectional area and volume of the upper airway region and the surrounding bony frame were measured. The association between ageing and upper airway morphology was analysed.
Soft palate length, minimum cross-sectional area of the retroglossal region, lateral dimensions at the minimum cross-sectional area of the retropalatal and retroglossal regions, nasopharyngeal volume, and average cross-sectional area of the nasopharyngeal region were found to significantly increase with ageing in all patients, while the upper airway shape flattened with ageing. The volume of the retropalatal region increased with ageing among the patients with a body mass index of less than 24 kg/m2. The volume of parapharyngeal fat pad increased with ageing among patients with a body mass index greater than 28 kg/m2.
A number of dimensional, cross-sectional and volumetric parameters of the pharynx increased with age, indicating that non-anatomical factors may play a more important role in the pathogenesis of obstructive sleep apnoea in aged patients.
Perinatal depression threatens the health of maternal women and their offspring. Although screening programs for perinatal depression exist, non-uptake of referral to further mental health care after screening reduces the utility of these programs. Uptake rates among women with positive screening varied widely across studies and little is known about how to improve the uptake rate. This study aimed to systematically review the available evidence on uptake rates, estimate the pooled rate, identify interventions to improve uptake of referral and explore the effectiveness of those interventions.
This systematic review has been registered in PROSPERO (registration number: CRD42019138095). We searched Pubmed, Web of Science, Cochrane Library, Ovid, Embase, CNKI, Wanfang Database and VIP Databases from database inception to January 13, 2019 and scanned reference lists of relevant researches for studies published in English or Chinese. Studies providing information on uptake rate and/or effectiveness of interventions on uptake of referral were eligible for inclusion. Studies were excluded if they did not report the details of the referral process or did not provide exact uptake rate. Data provided by observational studies and quasi-experimental studies were used to estimate the pooled uptake rate through meta-analysis. We also performed meta-regression and subgroup analyses to explore the potential source of heterogeneity. To evaluate the effectiveness of interventions, we conducted descriptive analyses instead of meta-analyses since there was only one randomised controlled trial (RCT).
Of 2302 records identified, 41 studies were eligible for inclusion, including 39 observational studies (n = 9337), one quasi-experimental study (n = 43) and one RCT (n = 555). All but two studies were conducted in high-income countries. The uptake rates reported by included studies varied widely and the pooled uptake rate of referral was 43% (95% confidence intervals [CI] 35–50%) by a random-effect model. Meta-regression and subgroup analyses both showed that referral to on-site assessment or treatment (60%, 95% CI 51–69%) had a significantly higher uptake rate than referral to mental health service (32%, 95% CI 23–41%) (odds ratio 1.31, 95% CI 1.13–1.52). The included RCT showed that the referral intervention significantly improved the uptake rate (p ＜ 0.01).
Almost three-fifths of women with positive screening results do not take up the referral offers after perinatal depression screening. Referral to on-site assessment and treatment may improve uptake of referral, but the quality of evidence on interventions to increase uptake was weak. More robust studies are needed, especially in low-and middle-income countries.
Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.
Distinguishing between hypertrophic cardiomyopathy and other causes ofleft ventricular hypertrophy can be difficult in children. We hypothesised that cardiac MRI T1 mapping could improve diagnosis of paediatric hypertrophic cardiomyopathy and that measures of myocardial function would correlate with T1 times and extracellular volume fraction.
Thirty patients with hypertrophic cardiomyopathy completed MRI with tissue tagging, T1-mapping, and late gadolinium enhancement. Left ventricular circumferential strain was calculated from tagged images. T1, partition coefficient, and synthetic extracellular volume were measured at base, mid, apex, and thickest area of myocardial hypertrophy. MRI measures compared to cohort of 19 healthy children and young adults. Mann–Whitney U, Spearman’s rho, and multivariable logistic regression were used for statistical analysis.
Hypertrophic cardiomyopathy patients had increased left ventricular ejection fraction and indexed mass. Hypertrophic cardiomyopathy patients had decreased global strain and increased native T1 (−14.3% interquartile range [−16.0, −12.1] versus −17.3% [−19.0, −15.7], p < 0.001 and 1015 ms [991, 1026] versus 990 ms [972, 1001], p = 0.019). Partition coefficient and synthetic extracellular volume were not increased in hypertrophic cardiomyopathy. Global native T1 correlated inversely with ejection fraction (ρ = −0.63, p = 0.002) and directly with global strain (ρ = 0.51, p = 0.019). A logistic regression model using ejection fraction and native T1 distinguished between hypertrophic cardiomyopathy and control with an area under the receiver operating characteristic curve of 0.91.
In this cohort of paediatric hypertrophic cardiomyopathy, strain was decreased and native T1 was increased compared with controls. Native T1 correlated with both ejection fraction and strain, and a model using native T1 and ejection fraction differentiated patients with and without hypertrophic cardiomyopathy.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity.
We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis.
Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69–410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion.
Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.
Flow over aligned and staggered cube arrays is a classic model problem for rough-wall turbulent boundary layers. Earlier studies of this model problem mainly looked at rough surfaces with a moderate coverage density, i.e.
is the surface coverage density and is defined to be the ratio between the area occupied by the roughness and the total ground area. At lower surface coverage densities, i.e.
, it is conventionally thought that cubical roughness acts like isolated roughness elements; and that the single-cube drag coefficient, i.e.
is the drag force on one cubical roughness element,
is the fluid density,
is the height of the cube,
is the spatially and temporally averaged wind speed at the cube height, and
is the drag coefficient of an isolated cube. In this work, we conduct large-eddy simulations and direct numerical simulations of flow over wall-mounted cubes with very low surface coverage densities, i.e.
. The large-eddy simulations are at nominally infinite Reynolds numbers. The results challenge the conventional thinking, and we show that, at very low surface coverage densities, the single-cube drag coefficient may increase as a function of
. Our analysis suggests that this behaviour may be attributed to secondary turbulent flows. Secondary turbulent flows are often found above spanwise-heterogeneous roughness. Although the roughness considered in this work is nominally homogeneous, the secondary flows in our simulations are very similar to those observed above spanwise-heterogeneous surface roughness. These secondary vortices redistribute the fluid momentum in the outer layer, leading to high-momentum pathways above the wall-mounted cubes and low-momentum pathways at the two sides of the wall-mounted cubes. As a result, the spatially and temporally averaged wind speed at the cube height, i.e.
, is an underestimate of the incoming flow to the cubes, which in turn leads to a large drag coefficient