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Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits, which has been implicated in Alzheimer's disease and major depressive disorder (MDD). However, the relationship between SAP level and depression severity remains obscure. The aims of this study were to investigate how SAP is involved in depression and to explore the association between SAP level and antidepressant treatment response. Patients with MDD (n = 85) who received escitalopram monotherapy for 8-12 weeks were selected from a multicenter open-label randomized clinical trial. The same number of healthy controls was recruited. Depression severity was measured according to the Hamilton Depression Rating Scale (HAMD-17) at baseline and weeks 4, 8, and 12. The plasma levels of SAP were measured at baseline, week 2 and week 12. As a result, baseline levels of SAP were significantly higher in depressed patients than in control subjects (p 0.001). SAP levels at baseline were negatively associated with depression severity after escitalopram treatment (p 0.05), and the changes in SAP levels from baseline to week 12 were highly correlated with the severity of depressive symptoms based on the HAMD-17 score (p 0.05). Interestingly, treatment with escitalopram significantly decreased the plasma levels of SAP in females, but not in males. Altogether, our results suggest that SAP not only involved in the pathobiology of depression but also mediates the action of antidepressant medications.

Memory is better for emotional rather than neutral events or materials (emotional enhancement of memory; EEM). Evidence suggests that this memory benefit remains intact in schizophrenia, but conflicting findings present the need for further research to understand how and when this process occurs. Here, we examine whether different encoding methods for learning emotional faces may result in different EEM patterns in those with schizophrenia spectrum disorders (SSD). A patient group (n = 28) and healthy comparisons (n = 29) encoded faces in two conditions that manipulated attentional focus to promote direct (emotion judgements) or indirect (sex discrimination) processing of emotional content. Based on literature in schizophrenia showing selective emotion perception deficits on tasks of direct processing but relatively intact emotion perception on indirect processing tasks, we hypothesized that patients would show greater EEM effects when faces were encoded indirectly. This hypothesis was not supported, and the patient group instead showed a similar intact EEM for angry and fearful faces to healthy comparisons in both encoding conditions. Further, using the Remember/Know paradigm, we demonstrated that the EEM in SSD appears selective to recollection-based memory, which helps to explain inconsistencies in past literature that has not differentiated between recognition domains. These findings have important implications for improving emotional memory and functional outcomes in SSD; future research should establish how the EEM for facial expressions may relate to social functioning.

Background Post-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects Objective/hypothesis To test the use of ECT to disrupt the reconsolidation of traumatic memories as a potential treatment for PTSD Methods Participants were adults from the civilian population and were referred for ECT treatment for severe depression with comorbid PTSD symptoms. Twenty-eight participants were randomly assigned to reactivation of a traumatic or non-traumatic memory using audio script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included a comparison of the change in heart rate while listening to the script Results Twenty-five female patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time Conclusions ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory reactivation. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04027452 . Identifier NCT04027452.

Purpose To present the visual and safety outcomes of surgery for primary idiopathic macular holes including predictors of visual acuity and the impact of combined phacovitrectomy surgery. Design Registry-style, prospective, nonrandomized, observational cohort study. Participants Patients with idiopathic macular holes undergoing primary surgery. Methods Surgeons were invited to submit clinical details of all macular hole cases receiving surgery. Baseline demographic and clinical information, and details of surgical intervention were collected. Primary follow-up data were collected at 3 months postoperatively or before revision surgery, and surgeons were also asked to submit data at 12 and 24 months postoperatively. Main Outcome Measures Visual acuity improvement ≥15 letters and ≥0 letters, change in mean visual acuity, visual acuity ≥70 letters (20/40), retinal detachment, and endophthalmitis. Results A total of 2455 eyes of 2366 patients were included in the study, and hole closure was achieved in 95.6% of eyes with a single procedure. Mean baseline vision was 48.3 letters. The proportion of successful eyes improving ≥15 letters at 3, 12, and 24 months was 59.1%, 69.4%, and 68.2%, respectively. The mean improvement in acuity at 3, 12, and 24 months was 16.0, 19.2, and 23.6 letters, and 92.4%, 93.4%, and 95.8% improved ≥0 letters at 3, 12, and 24 months, respectively. Eyes receiving SF6 gas had better visual acuities at all time points postoperatively (adjusted effect 3.4, 3.1, and 4.6 letters better at 3, 12, and 24 months vs. longer-acting gas, respectively). Combined phacovitrectomy in phakic eyes was associated with better corrected visual acuity postoperatively (vs. vitrectomy surgery alone), a difference that vanished when eyes went on to have subsequent cataract surgery. The rate of retinal detachment postoperatively was 1.3%, and the odds of detachment were greater in eyes receiving longer-acting gases versus SF6 gas (adjusted odds ratio, 2.2; 95% confidence interval, 1.04–4.77; P = 0.039). There were no reported cases of endophthalmitis. Conclusions Macular hole surgery substantially improved acuity in approximately two thirds of patients and was seldom associated with loss of vision. SF6 gas was associated with better visual outcomes, an effect that warrants further study.

Background There have been inconsistencies in the histological abnormalities found in the cerebral cortex from patients with schizophrenia, bipolar disorder and major depression. Discrepancies in previously published reports may arise from small sample sizes, inconsistent methodology and biased cell counting. New Method We applied automated quantification of neuron density, neuron size and cortical layer thickness in vast regions of human cortex in psychiatric patients. This method accurately segments DAPI positive cells that are also stained with CUX2 and FEZF2. Cortical layer thickness, neuron density and neuron size were automatically computed for each cortical layer in numerous Brodmann areas. Results We did not find pronounced cytoarchitectural abnormalities in the anterior cingulate cortex or orbitofrontal cortex in patients with schizophrenia, bipolar disorder or major depressive disorder. Comparison with existing methods. There were no significant differences in layer thickness measured in immunohistochemically stained slides compared with traditional Nissl stained slides. Automated cell counts were correlated, reliable and consistent with manual counts, while being much less time-consuming. Conclusion We demonstrate the validity of using a novel automated analysis approach to post-mortem brain tissue. We were able to analyze large cortical areas and quantify specific cell populations using immunohistochemical markers. Future analyses could benefit from efficient automated analysis.

The Uniaxial Compressive Strength (UCS) of rock cores is a key parameter for design analysis of rock engineering projects such as rock tunnels and piles in rockets. Diametral and axial point load tests on cylinder cores have been used to obtain Point Load Strength Index (PLSI). This PLSI is correlated to UCS. Recently, point load tests on irregular lumps are also used to obtain PLSI which is then correlated to UCS. However, the data on this correlation are very limited, especially for Hong Kong rocks. This paper presents the methodology for specimen preparation, testing, and data analysis. Results from irregular lump point load tests, diametral and axial point load tests, and uniaxial compressive tests (a total of 754 specimens of granitic rocks were tested) are then presented, analyzed, and discussed. A correlation between PLSI from irregular lump tests and UCS is established with a suitable size correction function. It is found that the I s(50) of the slightly decomposed Granite is between 7.31 MPa and 8.5 MPa. The I s(50) of the altered rock is 2.35 MPa, where the rock containing weakness plane is 5.59 MPa. The moderately decomposed Granite varies from 2.28 MPa to 4.92 MPa. The weathering affected the PLIS a lot. It is found that the values of power index value m in the size correction function is 0.443–0.600 for slightly decomposed granite (fine to coarse grains) and 0.545–5.562 for moderately decomposed granite (fine to medium and medium grains). Based on our study, for slightly decomposed coarse grain and fine to medium grain Granite, the size correction factor F = ( D e /50) 0.44 (lower bound) is recommend; while for all other weathering conditions and grain sizes, the size correction factor F = ( D e /50) 0.55 (lower bound) is recommended. The correlation between the UCS and PLSI Is (50) of irregular lumps is found to be 22.27, which is very close to the values of 21.61 and 21.72 for diametral and axial PL tests using the size correction factor of F = ( De /50) 0.45 . This indicates that the correlation between UCS and PLSI from point load tests on irregular lumps established in this paper is reliable.

Objective Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. Methods NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. Results ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. Conclusions ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer.

This study considers the effects of cyclic differential heating on the velocity of the subcritical crack growth (SCG) from a central notch in rock beams under four-point bending test. Beams of both Carrara marble and Fujian granite are subjected to non-uniform heating, with heating from the top surface containing the notch (at about 60° Celsius) and with cooling to the bottom side with no notch (at about 25° Celsius). Beams are heated for 7–188 days before they are subject to constant load creeping test under four-point bending configuration, and the compliance method is used to interpret crack growth from the crack mouth opening displacement (CMOD). The compliance method is verified by using acoustic emissions from cracking events together with simultaneous microscopic observations. It was discovered that a microcrack processing zone (PZ) was observed in the form of white patches ahead of the notch tip during the creeping test, followed by sudden jumps of macrocrack growth. Linear elastic fracture mechanics (LEFM) is used to calculate the local stress intensity factor, which is then further related to crack growth velocity, through the commonly adopted power law. After the application of non-uniform cyclic heating, the P-wave velocity of Fujian granite increases (due to microcrack closure) whilst that of Carrara marble decreases (due to parallel crack formation). The SCG parameters in the power law (power index n and threshold velocity v0) are obtained. There is no clear trend in the variation of the SCG parameters with the number of heating cycles. However, these parameters are used to simulate subcritical crack growth velocity for both heated and unheated specimens. In the light of fracture mechanics analysis, we conclude that Fujian granite is clearly preferable to Carrara marble in making rock panels on cladding of buildings.

Psychosocial adversity in early life increases the likelihood of mental and physical illness, but the underlying mechanisms are poorly understood. Mgat5 is an N-acetylglucosaminyltransferase in the Golgi pathway that remodels the N-glycans of glycoproteins at the cell surface. Mice lacking Mgat5 display conditional phenotypes in behaviour, immunity, metabolism, aging and cancer susceptibility. Here we investigated potential gene-environment interactions between Mgat5 and early life adversity on behaviour and physiological measures of physical health. Mgat5(-/-) mutant and Mgat5(+/+) wild-type C57Bl/6 littermates were subject to maternal separation or foster rearing as an early life stressor, in comparison to control mice reared normally. We found an interaction between Mgat5 genotype and maternal rearing condition in which Mgat5(-/-) mice subjected to early life stress had lower glucose levels and higher bone density. Mgat5(-/-) genotype was also associated with less immobility in the forced swim test and greater sucrose consumption, consistent with a less depression-like phenotype. Cortical neuron dendrite spine density and branching was altered by Mgat5 deletion as well. In general, Mgat5 genotype affects both behaviour and physical outcomes in response to early life stress, suggesting some shared pathways for both in this model. These results provide a starting point for studying the mechanisms by which protein N-glycosylation mediates the effects of early life adversity.

Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior.

Neuronal calcium sensor-1 or Frequenin is a calcium sensor widely expressed in the nervous system, with roles in neurotransmission, neurite outgrowth, synaptic plasticity, learning, and motivated behaviours. Neuronal calcium sensor-1 has been implicated in neuropsychiatric disorders including autism spectrum disorder, schizophrenia, and bipolar disorder. However, the role of neuronal calcium sensor-1 in behavioural phenotypes and brain changes relevant to autism spectrum disorder have not been evaluated. We show that neuronal calcium sensor-1 deletion in the mouse leads to a mild deficit in social approach and impaired displaced object recognition without affecting social interactions, behavioural flexibility, spatial reference memory, anxiety-like behaviour, or sensorimotor gating. Morphologically, neuronal calcium sensor-1 deletion leads to increased dendritic arbour complexity in the frontal cortex. At the level of hippocampal synaptic plasticity, neuronal calcium sensor-1 deletion leads to a reduction in long-term potentiation in the dentate gyrus, but not area Cornu Ammonis 1. Metabotropic glutamate receptor-induced long-term depression was unaffected in both dentate and Cornu Ammonis 1. These studies identify roles for neuronal calcium sensor-1 in specific subregions of the brain including a phenotype relevant to neuropsychiatric disorders.

This study investigates the changes in the ultrasonic and mechanical properties of a rock, by means of ultrasonic wave velocity measurements on a brittle limestone containing natural fractures and bedding subjected to uniaxial compression tests . The results showed that natural fractures and bedding reduced the velocity of ultrasonic waves and the mechanical strength of the limestone. Combined with the analysis of X-ray CT images of the samples, we found that the orientations of the bedding and of the pre-existing penetrating fractures affected the direction of subsequent crack propagation under uniaxial compressional loading. The initial disturbance factor D and the intactness factor s were calculated through the use of equivalent medium theory and Hoek–Brown strength model. The relationship between s and D was empirically characterized by an exponential fitting. A parameter b was introduced that can be calculated from the s–D relationship. This parameter represents a strength index for the pre-existing natural fractures. Based on the value of b, the limestones studied were classified into four types: fissures and bedding, infilled fractures and bedding, main infilled fractures, and nearly intact.

This study investigated the change of stress with crack development, using the numerical code RFPA3D, so as to understand the crack coalescence mechanisms occurring within a heterogeneous solid containing multiple holes loaded in a state of uniaxial compression. A full discussion is presented on a statistical analysis of observed microcracks data, and on the appropriate parameter selection based on those microcrack statistics. The simulated peak stress results and coalescence patterns using the selected parameters were found to closely resemble previous experimental observations. A full investigation and discussion of the stress distributions around holes during the crack growth and coalescence processes is presented for heterogeneous sample cases. Under applied loading, crack initiation, growth direction and coalescence pattern are strongly influenced by the shape of the interaction tensile zone formed between holes. Acoustic emission (AE) analysis in relation to the numerical simulations indicates that no case of pure tensile crack coalescence occurs between holes. Three modes of coalescence are classified: Ts mode (tensile mode coalescence with shear), MT mode (mixed mode coalescence with tensile mode dominant) and M mode (mixed mode coalescence). The crack coalescence mechanisms and patterns were further investigated by changing the parameters of normalized bridge length (d/r), bridge angle β and number of holes. A precise crack coalescence criterion is proposed.

The instability problem in the presence of multiple openings is complicated, depending not only on the in situ stress field and the rockmass geological condition, but also on the size, distribution and the distances between the multiple openings. The aim of the experimental study presented in this paper is to examine crack initiation and coalescence mechanisms and failure behaviour in a granite material containing multiple holes under uniaxial compression. In this paper, the holes distribution in the samples were varied between array modes to random mode with varied hole separation distances ‘ d ’ (or bridge length), bridge angles ‘ β ’ (angle between the line connecting the centres of two holes and the axial loading direction), hole diameter ‘2 r ’, and the number of holes in the specimen. The hole distribution strongly affects the stress for crack initiation, coalescence and peak value, and the scence patterns. The coalescence mechanisms for multiple hole samples depend on the bridge angle β and the normalized bridge length d / r . A criterion for coalescence mechanism related to holes distribution is proposed. The modified Sammis and Ashby (1986) [36] crack model can predict the peak stress and agree well with the experiment. Results analysis shows that peak stress depends primarily on number of holes coalescence, which is then used to effectively determine the hole defects ensuring integral stability of rockmass around tunnel.

Summary Current antipsychotic drugs primarily target dopamine D2 receptors (D2Rs), in conjunction with other receptors such as those for serotonin. However, these drugs have serious side effects such as extrapyramidal symptoms (EPS) and diabetes. Identifying a specific D2R signaling pathway that could be targeted for antipsychotic effects, without inducing EPS, would be a significant improvement in the treatment of schizophrenia. We report here that the D2R forms a protein complex with Disrupted in Schizophrenia 1 (DISC1) that facilitates D2R-mediated glycogen synthase kinase (GSK)-3 signaling and inhibits agonist-induced D2R internalization. D2R-DISC1 complex levels are increased in conjunction with decreased GSK-3α/β (Ser21/9) phosphorylation in both postmortem brain tissue from schizophrenia patients and in Disc1 -L100P mutant mice, an animal model with behavioral abnormalities related to schizophrenia. Administration of an interfering peptide that disrupts the D2R-DISC1 complex successfully reverses behaviors relevant to schizophrenia but does not induce catalepsy, a strong predictor of EPS in humans. Video Abstract

Objective To improve antipsychotic treatment in schizophrenia patients, many studies have investigated genetic polymorphisms associated with antipsychotic metabolizing enzymes and receptors. While these studies have typically focused on drug response, few have investigated genetic influences on antipsychotic dosage. This study set out to analyze the association between 134 SNPs in 38 candidate genes and antipsychotic dosage in schizophrenia patients. Methods For our analysis, 300 patients with a diagnosis of either schizophrenia or schizoaffective disorder were recruited between the ages of 18 and 75. A cross-sectional assessment was used, in which data were collected from each participant through an interview and self-report questionnaire. Antipsychotic dose was standardized according to the chlorpromazine equivalents, defined daily dose and relative to the maximum dose specified in the product monograph. Participants were genotyped using a Customized Illumina Chip comprising 134 SNPs, and all markers were screened for nominal significance. Results The analysis showed a nominally significant association with the GFRA1 gene. Conclusion The common variants investigated in this study had no major influence on the antipsychotic dosage prescribed in study participants. It remains, though, that this strategy may prove valuable clinically and warrants further investigation.

In this paper, we describe the design, construction and performance of an apparatus installed in the Aberdeen Tunnel laboratory in Hong Kong for studying spallation neutrons induced by cosmic-ray muons under a vertical rock overburden of 611 m water equivalent (m.w.e.). The apparatus comprises six horizontal layers of plastic-scintillator hodoscopes for determining the direction and position of the incident cosmic-ray muons. Sandwiched between the hodoscope planes is a neutron detector filled with 650 kg of liquid scintillator doped with about 0.06% of Gadolinium by weight for improving the efficiency of detecting the spallation neutrons. Performance of the apparatus is also presented.

Background Suicide is the act of intentionally causing one's own death. The lifetime suicide risk in schizophrenia is 4.9% and 20% to 50% of patients with SCZ will attempt suicide during their life. The other risk factors for suicidal behavior in schizophrenia include prior history of suicide attempts, active psychosis, depression and substance abuse. To date, there are no robust genetic or epigenetic predictors of suicide or suicide attempt in this specific population. Methods We collected detailed clinical information and DNA samples from 241 schizophrenia patients and performed the genetic analyses in suicide attempters and non-attempters, among these patients. Using the structured research interview, we determined the presence of suicide attempt lifetime and then we tested 384 DNA variants in candidate genes supposed to be involved in the neurobiology of schizophrenia. We applied a novel mapping analysis using a specific bioinformatic tool that analyzed only the polymorphic CpG sites in our SNP panel. This analysis looked at the presence or absence of methylation sites affected by the SNP allele. The SNPs in the candidate genes were studied under a different perspective considering their direct contribution to the availability of methylation sites within the gene of interest. The level of potential methylation was compared using a linear model in attempters and non-attempters. Results Among the 384 SNPs selected from the Illumina Bead Chip only the rs2661319 in the RGS4 gene was significantly associated with suicide attempt (p = 0.002). There were 119 CpG SNPs in the aforementioned panel. The gene-wise potential methylation level of RGS4 was 55% in the attempters and 65% in the non-attempters with a p-value of 0.005. The total level of potential metylation in the overall panel (119 SNPs combined) was not associated with suicide attempt. However, when considering the potential methylation at chromosome 1, we found that suicide attempt (p = 0.036) was associated with lower methylation. Discussion The overall results showed no strong association between CpG SNPs and suicide attempt but the information regarding the CpG SNP potential methylation could be used as covariate in future methylation analysis.

Schizophrenia and substance use disorders (SUD) often occur together, yet it is unclear why this is the case or how best to manage dual diagnosis. Rodent models are well suited to study how genes and environment interact to impact neurodevelopment, brain function and behaviors relevant to dual diagnosis. Indeed a variety of rodent models for schizophrenia display behavioral and physiological features relevant to SUD including: neurodevelopmental models, models of a rare variant (Disc1), to models of common variants (neurexin, dysbindin and neuregulin), and models of various gene-drug interactions. Thus it may be worthwhile to probe models of schizophrenia for insights relevant to SUD and dual diagnosis. However, future studies on dual diagnosis should involve characterization beyond measuring locomotor responses to self-administration tasks, include drug classes other than psychostimulants, and dissect the neuroadaptations that underlie risk for dual diagnosis.

Bacterial concentration (Escherichia coli) is generally adopted as a key indicator of beach water quality. Currently the beach management system in Hong Kong relies on past water quality data sampled at intervals between 3 and 14 days. Beach advisories are issued when the geometric mean E. coli level of the past five samples exceeds the beach water quality objective (WQO) of 180 counts/100 mL. When the E. coli level varies dynamically, the system is not able to track the daily bacterial variation. And yet worldwide there does not exist a generally accepted method to predict beach water quality in a marine environment, which is influenced by hydro-meteorological variables, catchment characteristics, as well as complicated tidal currents and wave effects. A comprehensive study of beach water quality prediction has been carried out for four representative beaches in Hong Kong: Big Wave Bay (BW), Deep Water Bay (DW), New Cafeteria (NC) and Silvermine Bay (SIL). Statistical analysis of the extensive regular monitoring data was carried out for two periods before and after the commissioning of the Harbour Area Treatment Scheme (HATS): (1990–1997) and (2002–2006) respectively. The data analysis shows that E. coli is strongly correlated with seven hydro-environmental variables: rainfall, solar radiation, wind speed, tide level, salinity, water temperature and past E. coli concentration. The relative importance of the parameters is beach-specific, and depends on the local geographical and hydrographical characteristics as well as location of nearby pollution sources. Multiple Linear Regression (MLR) and Artificial Neural Network (ANN) models are developed from the sparsely sampled regular monitoring data (2002–2006) to predict the next-day E. coli concentration using the key hydro-environmental variables as input parameters. The models are validated against daily monitoring data in the bathing seasons of 2007 and 2008. The models are able to track the dynamic changes in E. coli concentration and predict WQO compliance/exceedance with an overall accuracy of 70–96%. Both the MLR and ANN models are superior to the current beach advisories in capturing water quality variations, and in predicting WQO exceedances. For example, the models predict around 80% and 50% of the exceedances at BW and NC respectively in June–July 2007, as compared to 0% and 14% based purely on past data. Similarly, observed exceedances are predicted with success rates of 71%, 42%, and 53% at BW, NC, and SIL respectively during July–October 2008, as compared with 0%, 0%, and 6% using the current water quality assessment criterion. The MLR and ANN models have similar performances; ANN model tends to be better in predicting the high-end concentrations, with however a greater number of false positive predictions (false alarms). This work demonstrates the practical feasibility of predicting bacterial concentration based on the critical hydro-environmental variables, and paves the way for developing a real time water quality forecast and management system for Hong Kong.

DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene–environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia. We hypothesized that gene–environment interactions would affect behavior in a mutant Disc1 mouse model. We examined the effect of chronic social defeat (CSD) as an environmental stressor in two lines of mice carrying different Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and the social interaction task for sociability and social novelty (SSN). We found that Disc1-L100P +/− and wild-type mice have similar anxiety responses to CSD, while Q31L +/− mice had a very different response. We also found evidence of significant gene–environment interactions in the OF, EPM and SSN.

The glutamate neurotransmitter system is one of the major candidate pathways for the pathophysiology of schizophrenia, and increased understanding of the pharmacology, molecular biology and biochemistry of this system may lead to novel treatments. Glutamatergic hypofunction, particularly at the NMDA receptor, has been hypothesized to underlie many of the symptoms of schizophrenia, including psychosis, negative symptoms and cognitive impairment. This review will focus on d -serine, a co-agonist at the NMDA receptor that in combination with glutamate, is required for full activation of this ion channel receptor. Evidence implicating d -serine, NMDA receptors and related molecules, such as d -amino acid oxidase (DAO), G72 and serine racemase (SRR), in the etiology or pathophysiology of schizophrenia is discussed, including knowledge gained from mouse models with altered d -serine pathway genes and from preliminary clinical trials with d -serine itself or compounds modulating the d -serine pathway. Abnormalities in d -serine availability may underlie glutamatergic dysfunction in schizophrenia, and the development of new treatments acting through the d -serine pathway may significantly improve outcomes for many schizophrenia patients. This article is part of a Special Issue entitled ‘Schizophrenia’.

Internal waves have been implicated in the cross-shore transport of scalars such as larvae, nutrients, and pollutants at locations around the world. The present study combines physical measurements with a comprehensive set of surf zone water quality measurements to evaluate the possible impact of cross-shore internal wave transport on surf zone water quality during two study periods. An array of oceanographic moorings was deployed in the summer of 2005 and 2006 at 10–20 m depth offshore of the beach to observe internal waves. Concurrently, surf zone water quality was assessed twice daily at night at an adjacent station (Huntington State Beach) by measuring concentration of phosphate, dissolved inorganic nitrogen (DIN), silicate, chlorophyll a, fecal indicator bacteria (FIB), and the human-specific fecal DNA marker in Bacteroidales . The baroclinic component accounted for about 30% of the total variance in water column velocity, indicating the importance of density-driven flow during the summer when the water column was stratified. Arrival of cold subthermocline water in the very nearshore (within 1 km of the surf zone) was characterized by strong baroclinic onshore flow near the bottom of the water column. The near bottom, baroclinic, cross-shore current was significantly lag-correlated with the near bottom temperature data along a cross-shore transect towards shore, demonstrating shoreward transport of cold subthermocline water. Wavelet analysis of temperature data showed that non-stationary temperature fluctuations were correlated with buoyancy frequency and the near bottom cross-shore baroclinic current. During periods of large temperature fluctuations, the majority of the variance was within the semi-diurnal band; however, the diurnal and high frequency bands also contained a substantial fraction of total variance. The bottom cross-shore baroclinic current was proposed as a proxy for shoreward transport potential by internal waves and was positively correlated with phosphate concentration in both years, silicate in 2005, and fecal indicator bacteria measurements in 2006. The results suggest internal waves are an important transport mechanism of nutrient-rich subthermocline water to the very nearshore in the Southern California Bight, and may facilitate the transport of FIB into the surf zone or enhance persistence of land-derived FIB.

This work aimed to understand the distribution of five bacterial pathogens in O'ahu coastal streams and relate their presence to microbial indicator concentrations, land cover of the surrounding watersheds, and physical-chemical measures of stream water quality. Twenty-two streams were sampled four times (in December and March, before sunrise and at high noon) to capture seasonal and time of day variation. Salmonella, Campylobacter, Staphylococcus aureus, Vibrio vulnificus, and V. parahaemolyticus were widespread -12 of 22 O'ahu streams had all five pathogens. All stream waters also had detectable concentrations of four fecal indicators and total vibrio with log mean ± standard deviation densities of 2.2 ± 0.8 enterococci, 2.7 ± 0.7 Escherichia coli, 1.1 ± 0.7 Clostridium perfringens, 1.2 ± 0.8 F(+) coliphages, and 3.6 ± 0.7 total vibrio per 100 ml. Bivariate associations between pathogens and indicators showed enterococci positively associated with the greatest number of bacterial pathogens. Higher concentrations of enterococci and higher incidence of Campylobacter were found in stream waters collected before sunrise, suggesting these organisms are sensitive to sunlight. Multivariate regression models of microbes as a function of land cover and physical-chemical water quality showed positive associations between Salmonella and agricultural and forested land covers, and between S. aureus and urban and agricultural land covers; these results suggested that sources specific to those land covers may contribute these pathogens to streams. Further, significant associations between some microbial targets and physical-chemical stream water quality (i.e., temperature, nutrients, turbidity) suggested that organism persistence may be affected by stream characteristics. Results implicate streams as a source of pathogens to coastal waters. Future work is recommended to determine infectious risks of recreational waterborne illness related to O'ahu stream exposures and to mitigate these risks through control of land-based runoff sources.

GDNF (glial-cell-line derived neurotrophic factor) is a potent neurotrophic factor for dopaminergic neurons. Neuropsychiatric diseases and their treatments are associated with alterations in the levels of both GDNF and its receptor family (GDNF family receptor alpha or GFRA). GFRA1, GFRA2 and GFRA3 are located in chromosomal regions with suggestive linkage to schizophrenia. In this study we analyzed polymorphisms located in all four known GFRA genes and examined association with schizophrenia and clozapine response. We examined SNPs across the genes GFRA1-4 in 219 matched case-control subjects, 85 small nuclear families and 140 schizophrenia patients taking clozapine for 6months. We observed that GFRA3 rs11242417 and GFRA1 rs11197557 variants were significantly associated with schizophrenia after combining results from both schizophrenia samples. Furthermore, we found an overtransmission of the G-C GFRA1 rs7920934-rs730357 haplotype to subjects with schizophrenia and association of A-T-G-G GFRA3 rs10036665-rs10952-rs11242417-rs7726580 with schizophrenia in the case-control sample. On the other hand, GFRA2 variants were not associated with schizophrenia diagnosis but subjects carrying T-G-G rs1128397-rs13250096-rs4567028 haplotype were more likely to respond to clozapine treatment. The statistical significance of results survived permutation testing but not Bonferroni correction. We also found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia.

Suicide is an act deliberately initiated and performed by a person with full knowledge that a fatal outcome is probable. The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis of suicidal behaviour by a genetic association between the 5-HT2A T102C silent polymorphism and suicidality in patients with mood disorders and schizophrenia. However, a recent meta-analysis failed to confirm this association. We developed an improved quantitative assay for the measurement of allele-specific methylation of the 5-HT2A gene, and found that the methylation of the C allele in the pre-frontal cortex of heterozygous suicide victims ( n = 10) was not significantly different in comparison with the non-suicide group ( n = 10) ( p = 0.084). We also analyzed methylation of the C allele in white blood cell DNA from bipolar and schizophrenic attempters and found a significant difference in the schizophrenic attempters ( p = 0.00013) but not in the bipolar attempters ( p = 0.616). Because the 5-HT2A gene is subject to imprinting, the parent-of-origin may affect inheritance of suicidal behaviour. Thus, we examined the parental origin of specific alleles for genetic association in a genetic family-based sample of major psychoses in which information on suicidal behaviour was available. This result suggests that methylation of the 102C allele does not influence completed suicide.

Purpose: Patients with myelodysplastic syndrome (MDS) and iron overload (IOL) often receive iron chelation therapy (ICT); however, data on clinical outcomes are limited. We reviewed 178 patients with MDS to determine the effect of ICT on survival. Patients and Methods: Data were collected by chart review and survival analysis performed. A subgroup analysis compared control patients with clinical features similar to patients who received ICT. Results: French-American-British MDS subtypes for patients were as follows: refractory anemia (RA), n = 36; RA with ringed sideroblasts, n = 42; RA with excess blasts (RAEB), n = 28; RAEB in transformation or acute myeloid leukemia (AML), n = 16; chronic myelomonocytic leukemia, n = 25; other, n = 31. International Prognostic Scoring System (IPSS) scores were as follows: low risk, n = 44; intermediate-1 risk, n = 55; intermediate-2 risk, n = 17; high risk, n = 17. Eighteen patients received ICT; median duration was 21.6 months (range, 1.3-151 months). In univariate analysis (UVA), factors significant for overall survival (OS) were IPSS score; MDS subtype; number of red blood cell (RBC) units transfused; MDS treatment; elevated ferritin; clinical IOL; receiving ICT (P < .05 for all); and age (P = .01). In multivariate analysis (MVA), significant factors included IPSS score (P = .008; hazard ratio [HR], 2.2 [95% CI, 1.3-3.7]) receiving ICT (P = .02; HR, 0.2 [95% CI, 0.01-1.0]). For low/intermediate-1 risk IPSS score, 4-year OS was 64% for patients receiving ICT and 43% for patients not receiving ICT (P = .003). An MVA was performed, including number of cytopenias; blast count; karyotype; AML transformation; ≥ 1 serious infection (P < .05 in UVA for all) with MDS treatment; number of RBC units transfused; and clinical IO; receipt of iron chelation therapy determined that factors significant for OS were infection (P = .05; HR, 3.2 [95% CI, 0.97-10.4]) and ICT (P = .02). Improved OS was maintained in the subgroup analysis (P = .01; HR, 0.29 [95% CI, 0.1-0.79]). Conclusion: Patients with MDS and IOL receiving ICT had improved survival compared with patients not receiving ICT, suggesting a possible beneficial effect on clinical outcome. Prospective studies of ICT in MDS are warranted.

To investigate the proportion of Chinese patients with intractable seizures and the risk factors leading to refractory epilepsy.Consecutive patients over 14 years of age attending a Neurology clinic were evaluated. Patients with epilepsy were classified into two groups according to their seizure control: refractory or seizure-free. Epilepsy was classified as idiopathic as defined by age-related onset and typical electroclinical characteristics, symptomatic if secondary to a structural abnormality and cryptogenic if the cause was unknown. Age, sex, epilepsy syndrome classification, aetiology, presence of mental retardation and the number of drugs used were compared between patients with refractory epilepsy and those in remission.Among 260 adolescent and adult patients with a mean age of 34 years (range 15-79), complete seizure control was achieved in 157 (60%) cases. Multivariate binomial logistic regression analysis showed that patients with mesial temporal sclerosis (OR=7.6, 95% CI 3.53-16.4, p0.01) and the presence of mental retardation (OR=9.39, 95% CI 3.98-22.12, p0.01) were more likely to develop pharmacoresistant epilepsy.In adults the underlying aetiology is an important factor as to whether patients develop intractable seizures. Poor control was also associated with the presence of mesial temporal sclerosis and mental retardation.

Direct shear tests on concrete specimens were conducted to investigate the shearing behaviour of the material under varying normal confining stresses. Test results were analyzed to quantify the mobilization of shear strength components derived from hydrated cement paste–aggregate adhesion, contact friction, shear dilation, and cement–aggregate interlock along the sheared surface under direct shearing. It was found that each component has its unique response in terms of mobilized shear stress and shear displacement. In addition, different modes of failure observed in uniaxial compression, splitting tension, and direct shear tests were identified to delineate the Mohr–Coulomb failure envelope for shear strength of concrete material.

Statistics of the mechanical and failure properties on the grain scale are often assumed to follow the Weibull distribution in numerical simulations of failure and damage development. To investigate the microstructural basis for such a statistical model of compressive failure in a brittle rock, we consider the development of instability in a wing crack model and establish a methodology whereby the Weibull parameters can be inferred from microstructural data on microcrack density and length statistics for input into finite element simulations. Application of this methodology to six Yuen Long marble samples provides important insights into how different attributes of the microstructure may influence the progressive development of rock failure. The finite element simulations underscore the significant influence of microcrack length statistics, which has not been emphasized in continuum damage mechanics models that usually emphasize the roles of average crack size and crack density. The microstructural data indicate that strength heterogeneity increases with increasing grain size, and this plays a key role in lowering the uniaxial compressive strength, which contributes to the overall decrease of strength with increasing grain size.

The NR2B protein is a critical structural and functional subunit of the NMDA glutamate receptor. The glutamate neurotransmitter system has been implicated in psychosis and schizophrenia, and so we looked for genetic association and measured gene expression in human DNA and brain samples, respectively, of the GRIN2B gene that codes for the NR2B protein. We tested three genetic polymorphisms: G-200T (5′UTR), A5806C and T5988C (both 3′UTR) in 180 matched schizophrenia case–control pairs, 86 schizophrenia nuclear family trios, and 318 bipolar disorder trios (of which 158 probands had psychotic symptoms). We measured brain GRIN2B mRNA levels in schizophrenia, bipolar disorder and unaffected controls (n = 35 each). We detected genetic association between the G-200T marker and schizophrenia (p = 0.002), between T5988C and bipolar disorder (p = 0.02), and between A5806C and bipolar disorder with psychotic symptoms (p = 0.0038). The T–C–C haplotype was transmitted more frequently with bipolar disorder, but less often with schizophrenia, while the G–C–T haplotype was transmitted more often in schizophrenia. Significant differences were found in overall haplotype frequencies between schizophrenia cases and controls (p = 0.005). GRIN2B expression levels in schizophrenia, bipolar disorder and controls were not significantly different. The genetic findings suggest a role for GRIN2B in schizophrenia and bipolar disorder.

Under uniaxial compression, brittle solids are frequently observed to fail by splitting parallel to the direction of loading. Although this failure has long been recognized, considerable confusion regarding how such splitting mechanisms develops still remains. Axial propagation of a crack-like flaw inclined to the loading direction of compression is one of the accepted mechanisms. In this paper, the axial propagation of a pore-like flaw as one of the mechanisms of splitting failure is approached. A series of physical and numerical tests of uniaxial compression on samples containing a single hole with varied diameters and sample widths are carried out to investigate the splitting failure, the failure modes and strength characterization due to crack growth from such flaw. Samples made from the Hong Kong granite are used in the physical tests to study the inference of heterogeneity of solid on crack growth. A Material Failure Process Analysis code (MFPA 2D ) is used as a numerical simulation tool to compare and explain the mode of failure from experiment. Sammis and Ashby [Sammis, C.G., Ashby M.F., 1986. The failure of brittle porous solids under compressive stress states. Acta Metall. 34, 511–526] theoretical crack model is employed to study the inference of sample size and diameter of hole on peak strength.

Brittle solids, such as rock or concrete, may contain numerous randomly distributed micro-flaws (e.g. cracks, pores or weak inclusions). When they are loaded in compression, cracks may nucleate from these flaws. These cracks then continue to grow in a stable manner with the increasing axial compression, curving toward an orientation parallel to the direction of axial compression. Their propagation and interaction may lead to the collapse of the solid in a splitting mode. With a newly developed numerical code, MFPA2D (material failure process analysis), heterogeneous solids containing pre-existing single, triple and multi-pore-like flaws are numerically tested to study the mechanisms of compression-induced axial splitting. The interaction of growing cracks with the surfaces of the specimen and with each other in terms of stress field and failure modes is numerically analyzed in detail. Under uniaxial compressions, specimens containing holes in a diagonal array are more conducive to interaction than specimens containing holes arranged either in a horizontal or vertical array. Various parameters, such as hole diameter, specimen width, and the geometrical arrangement of hole locations, that characterize the growth process are quantified. Numerical results mimic the phenomena of experimentally observed splitting failure in brittle solids such as rocks in a realistic way.

Schizophrenia is a common and debilitating illness, characterized by chronic psychotic symptoms and psychosocial impairment that exact considerable human and economic costs. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, treatment, genetics and neurobiology of schizophrenia. Although studied extensively from a clinical, psychological, biological and genetic perspective, our expanding knowledge of schizophrenia provides only an incomplete understanding of this complex disorder. Recent advances in neuroscience have allowed the confirmation or refutation of earlier findings in schizophrenia, and permit useful comparisons between the different levels of organization from which the illness has been studied. Schizophrenia is defined as a clinical syndrome that may include a collection of diseases that share a common presentation. Genetic factors are the most important in the etiology of the disease, with unknown environmental factors potentially modulating the expression of symptoms. Schizophrenia is a complex genetic disorder in which many genes may be implicated, with the possibility of gene-gene interactions and a diversity of genetic causes in different families or populations. A neurodevelopmental rather than degenerative process has received more empirical support as a general explanation of the pathophysiology, although simple dichotomies are not particularly helpful in such a complicated disease. Structural brain changes are present in vivo and post-mortem, with both histopathological and imaging studies in overall agreement that the temporal and frontal lobes of the cerebral cortex are the most affected. Functional imaging, neuropsychological testing and clinical observation are also generally consistent in demonstrating deficits in cognitive ability that correlate with abnormalities in the areas of the brain with structural abnormalities. The dopamine and other neurotransmitter systems are certainly involved in the treatment or modulation of psychotic symptoms. These broad findings represent the distillation of a large body of disparate data, but firm and specific findings are sparse, and much about schizophrenia remains unknown.

The purpose of this study is to investigate experimentally the creeping damage and failure mechanism around an opening in rock-like material containing non-persistent joints. The jointed rock-like specimen is modelled by plaster material, and the underground excavation is simulated by drilling at a certain stress level. In our experimental studies, time evolutions of deformation are recorded at various applied vertical (σ1) and confining (σ3) stress. It is found that with a fixed σ1, tensile mode of creeping failure is dominant when the λ (σ3/σ1) is low (λ=1/3). But when λ is high (⩾1/2), shear mode of creeping failure is dominant. The creeping failure time decreases with the increased λ and stress ratio of σ1/σ1max (σ1max is the maximum stress of a jointed rock-like mass). Furthermore, for the excavation in a low stress level (σ1/σ1max⩽45%), no creeping damage around opening will occur. The stress ratio λ and σ1/σ1max are the important indices indicating the degree of instability of an opening after excavation.

Splitting failure of rock specimen containing pre-existing crack-like flaws under compression is numerically investigated using Rock Failure Process Analysis (RFPA2D). Crack growth from single, triple and multi-crack-like flaws contained in numerical specimens are studied. The analysis of parameters, such as angle and length of the flaws, specimen width and the arrangement of flaw locations, is conducted to examine its influence on the growth and coalescence behaviour. Flaw length, flaw location and stress interaction between the nearby flaws are found to be important factors affecting the behaviour of crack initiation, propagation and coalescence.

This paper presents experimentally obtained results for the coefficient of restitution for spherical boulders impacting on rock slopes. Plaster modeling material is used for casting both the boulders and slopes. It is observed that the normal component of the coefficient of restitution ( R n ) increases with the slope angle α , which agrees with Wu's observations (Trans. Res. Rec. 1–5 (1985) 1031). However, there appears to be no clear correlation between the tangential component of the coefficient of restitution ( R t ) and the slope angle α . When the ratio of the resultant velocities and the ratio of the kinetic energies before and after impacts are used to define the coefficient of restitution (i.e. R V and R E ), a very clear increasing trend in the coefficient of restitution with α is observed. When all data are plotted onto the R t − R n space, our laboratory data fall into the rock slope regime proposed by Fornaro et al. (In: D.G. Price (Ed.), Proceedings of the Sixth International Congress IAEG, Amsterdam, Balkema, Rotterdam, 1990, p. 2173) and also agree with those data gleaned from literature. In addition, the rotational kinetic energy E r , induced at each impact, increases with the slope angle α , achieves a maximum at about α =40°, before decreasing again to a negligible value at α =70°. A simple theoretical model is proposed to explain this observation based on the locking between the boulder and the slope during impact. The α -dependence of E r differs from the recommendation by the Japanese Railway Association that the induced rotational energy is about 10% of that of the translational kinetic energy.

NALCN (sodium leak channel, non-selective) is located on chromosome 13q (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464 schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We observed nominal association with rs9518320 and rs9518331, suggesting that NALCN is not related to schizophrenia risk.

Fractures in the forms of joints and microcracks are commonly found in natural rocks, and their failure mechanism strongly depends on the crack coalescence pattern between pre-existing flaws. However, the crack coalescence pattern of rock specimens containing three or more flaws has not been studied comprehensively. In this paper, we investigate experimentally crack coalescence and peak strength of rock-like materials containing three parallel frictional flaws. Three flaws are arranged such that one pair of flaws lines collinearly and the third flaw forms either a non-overlapping pattern or an overlapping pattern with the first flaw. It is found that the mechanisms of crack coalescence depend on the flaw arrangement and the frictional coefficient μ on the flaw surface. Two “rules of failure” for the specimens containing three flaws are proposed. Rule No. 1: the pair of flaws with a lower value of coalescence stress will dominate the process of coalescence. Rule No. 2: mixed and tensile modes of coalescence are always the dominant modes if the coalescence stress of the two pairs of flaws is very close (say within 5%). In addition, it is found that the peak strength of the specimens does not depend on the initial crack density but on the actual number of pre-existing flaws involved in the coalescence. Comparisons of pattern of crack coalescence with the numerical approach are given in Part II of this study, and the two results agree well. The research reported here provides increased understanding of the fundamental nature of rock failure in uniaxial compression.

To study the role of dopamine (DA) receptor expression on dopamine-mediated rotational behaviour, adenovirus expressing the lacZ reporter gene (AdCMVLacZ) or D2R expressing adenoviral vector (AdRSVD2) viruses, mediating expression of β-galactosidase and DAD2 receptors, respectively, were microinjected stereotactically into Sprague–Dawley rat striatum. Apomorphine stimulated rotational behaviour was measured in rats unilaterally injected with either AdCMVLacZ or AdRSVD2. No significant difference in rotational direction was observed until day 14 post-injection, when animals showed a tendency to rotate away from the injected side. Our data indicate that unilateral changes in receptor density mediated by a non-cell type selective adenoviral vector results in minor changes in rotational behavior. This suggests that supersensitivity in dopamine receptor signaling, rather than receptor levels per se, are the major factor in determining rotational response with dopamine agonist stimulation in unilateral striatal dopamine depleted animals.

For static compressions of spheres, a new stress analysis for isotropic elastic spheres compressed between two flat rigid platens is proposed by incorporating the Hertz contact stress. The predictions of the failure load for various sizes and strengths of spheres agree very well with our static experiments on a brittle plaster material. For dynamic compressions of spheres, a simple crushing analysis illustrates that the size of the contact zone can be estimated quite accurately in terms of the size of the sphere, the dynamic hardness, and the impact energy. Although the maximum contact force at failure is larger in the static case than that in the dynamic case, the energy required for fragmentation of the solid spheres is larger under dynamic test than under static test. Comparisons of the static and dynamic tests show that the impact energy required for fragmentation of a sphere can be approximated as 1.5 times of that for the static test. As expected, the impact energy for fragmentation increases monotonically with the size and strength of the spheres. The contact time at failure, however, does not exhibit a clear trend with the changes in size and strength of the spheres.

This paper investigates the pattern of crack coalescence and strength of a sandstone-like material containing two parallel inclined frictional cracks under uniaxial compression, with changing values of inclination of preexisting cracks α , bridge angle β (inclination between the inner tips of the two preexisting cracks), and the frictional coefficient μ on the surfaces of the preexisting cracks. Three main modes of crack coalescence are observed: the shear (S) mode (shear cracking between the two preexisting cracks); the mixed shear/tensile (M) mode (propagation of both wing and shear cracks within the bridge area); and the wing tensile (W) mode (coalescence of wing cracks from the tips of the preexisting cracks). The M-mode and W-mode of crack coalescence can further be divided into two and six types, respectively. Simple regime classifications of coalescence in the α – β space are proposed for different values of μ (=0.6, 0.7 and 0.9). In general, the S-mode mainly occurs when α=β or when β β *( α , μ )=a−b α , with both a and b depending on μ ; the M-mode dominates when β L > β > β *( α , μ ) (where β L ≈82.5°); and the W-mode is only observed when β > β L . However, more experiments are still required to refine the classification. The observed peak strength, in general, increases with μ . Our results show that the peak strength predicted by the Ashby and Hallam (1986) model basically agrees with experiments. A minimum occurs at about α =65° when the peak strength is plotted against α . For α >45°, the peak strength is essentially independent of the bridge angle β .

Summary We do not think the conclusion by Drs Irfan and Cheung that the strength-index conversion factor is about 24 for Hong Kong rocks is fully justified, at least not at this moment. The claim that “a substantial amount of test data available particularly on granitic and volcanic rocks and marble” is not substantiated by evidence. In particular, as discussed in Section (2)(iii) above, the valid number of available data summarized by Drs Irfan and Cheung for Hong Kong rocks is, actually, in the same order of those tested and presented by us [9]. Further studies are still needed before a conclusive statement can be made. Actually, a comprehensive experimental and theoretical programme has been proposed and funded recently. Therefore, a thorough study will be carried out shortly to verify the preliminary finding by us [1]. In conclusion, we think that we should be more sceptical about all empirical formulae devised based upon a particular set of data and should not adopt indiscriminately such formulae in Hong Kong or elsewhere without sufficient experimental and theoretical verification. Especially, for the present case that the adopted value of 24 may actually overestimate the strength prediction. Nevertheless, we wish to thank Drs Irfan and Cheung for initiating this discussion which, we are sure, will be useful to the rock mechanics community and should provide stimulus for further scientific research and progress in this area of rock mechanics.

Objective This is a comprehensive study designed to examine the association between specific clusters of neurological abnormalities and several clinically relevant aspects of schizophrenia such as positive and negative symptoms, neurocognitive deficits and psychosocial performance. Methods Thirty-seven clinically stable schizophrenic (DSM-III-R) patients maintained on antipsychotic medication were comprehensively examined and Convit's Quantified Neurologic Scale (QNS) was completed. In addition, patients' psychopathology was rated on the Positive and Negative Syndromes Scale (PANSS); psychosocial performance was rated on the Global Scale of Adaptive Functioning (GAF) and the Social Performance Schedule (SPS); and neurocognitive deficits were measured with a computer-assisted neurocognitive test battery, COGLAB. The association between these factors was determined using Pearson's correlation coefficients. Results Frontal and soft neurological scores on the QNS correlated significantly with negative syndrome scores (r=0.45–0.51, p