Primary and substance-induced psychotic disorders in methamphetamine users

This study investigates the rates of primary psychotic disorders (PPD) and substance induced psychotic disorders (SIPDs) in methamphetamine (MA) users accessing needle and syringe programs (NSPs). The aim was to determine if there are systematic differences in the characteristics of MA users with PPDs and SIPDs compared to those with no psychotic disorder. Participants were 198 MA users reporting use in the previous month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders (PRISM-IV). Current psychiatric symptoms and substance use were also measured. Just over half (N=101) of participants met DSM-IV criteria for a lifetime psychotic disorder, including 81 (80%) with a SIPD and 20 (20%) with a PPD. Those with a younger age of onset of weekly MA use were at increased risk of a lifetime SIPD. A current psychotic disorder was found in 62 (39%), comprising 49 SIPDs (79%) and 13 PPDs (21%). MA users with a current PPD were more likely to have received psychiatric treatment in the past month than those with a current SIPD, despite a similar level of psychotic symptom severity. A high proportion of MA users accessing NSPs have psychotic disorders, the majority of which are substance-induced.

BOSTER : an efficient algorithm for mining frequent unordered induced subtrees

Extracting frequent subtrees from the tree structured data has important applications in Web mining. In this paper, we introduce a novel canonical form for rooted labelled unordered trees called the balanced-optimal-search canonical form (BOCF) that can handle the isomorphism problem efficiently. Using BOCF, we define a tree structure guided scheme based enumeration approach that systematically enumerates only the valid subtrees. Finally, we present the balanced optimal search tree miner (BOSTER) algorithm based on BOCF and the proposed enumeration approach, for finding frequent induced subtrees from a database of labelled rooted unordered trees. Experiments on the real datasets compare the efficiency of BOSTER over the two state-of-the-art algorithms for mining induced unordered subtrees, HybridTreeMiner and UNI3. The results are encouraging.

γ-radiation-induced γH2AX formation occurs preferentially in actively transcribing euchromatic loci

The central dogma in radiation biology is that nuclear DNA is the critical target with respect to radiosensitivity. In accordance with the theoretical expectations, and in the absence of a conclusive model, the general consensus in the field has been to view chromatin as a homogeneous template for DNA damage and repair. This paradigm has been called into question by recent findings indicating a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin. Here, we have extended those studies and provide evidence that γH2AX foci form preferentially in actively transcribing euchromatin following γ-irradiation.

Androgen-targeted therapy-induced epithelial mesenchymal plasticity and neuroendocrine transdifferentiation in prostate cancer : an opportunity for intervention

Androgens regulate biological pathways to promote proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen receptor (AR) targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or AR function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation) has been shown to activate both epithelial-to-mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD) programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy) in multiple human cancer types. NEtD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen-targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.

Is there a potential relationship between prior h amstring strain injury and increased risk for future a nterior cruciate ligament injury?

Hamstring strain injuries (HSIs) are the most prevalent injury in a number of sports, and while anterior cruciate ligament (ACL) injuries are less common, they are far more severe and have long-term implications, such as an increased risk of developing osteoarthritis later in life. Given the high incidence and severity of these injuries, they are key targets of injury preventive programs in elite sport. Evidence has shown that a previous severe knee injury (including ACL injury) increases the risk of HSI; however, whether the functional deficits that occur after HSI result in an increased risk of ACL injury has yet to be considered. In this clinical commentary, we present evidence that suggests that the link between previous HSI and increased risk of ACL injury requires further investigation by drawing parallels between deficits in hamstring function after HSI and in women athletes, who are more prone to ACL injury than men athletes. Comparisons between the neuromuscular function of the male and female hamstring has shown that women display lower hamstring-to-quadriceps strength ratios during isokinetic knee flexion and extension, increased activation of the quadriceps compared with the hamstrings during a stop-jump landing task, a greater time required to reach maximal isokinetic hamstring torque, and lower integrated myoelectrical hamstring activity during a sidestep cutting maneuver. Somewhat similarly, in athletes with a history of HSI, the previously injured limb, compared with the uninjured limb, displays lower eccentric knee flexor strength, a lower hamstrings-to-quadriceps strength ratio, lower voluntary myoelectrical activity during maximal knee flexor eccentric contraction, a lower knee flexor eccentric rate of torque development, and lower voluntary myoelectrical activity during the initial portion of eccentric contraction. Given that the medial and lateral hamstrings have different actions at the knee joint in the coronal plane, which hamstring head is previously injured might also be expected to influence the likelihood of future ACL. Whether the deficits in function after HSI, as seen in laboratory-based studies, translate to deficits in hamstring function during typical injurious tasks for ACL injury has yet to be determined but should be a consideration for future work.

Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

Novel polymer synthesis methodologies using combination of thermally and photochemically-induced nitroxide mediated polymerisation

The combination of thermally- and photochemically-induced polymerization using light sensitive alkoxyamines was investigated. The thermally driven polymerizations were performed via the cleavage of the alkoxyamine functionality, whereas the photochemically-induced polymerizations were carried out either by nitroxide mediated photo-polymerization (NMP2) or by a classical type II mechanism, depending on the structure of the light-sensitive alkoxyamine employed. Once the potential of the various structures as initiators of thermally- and photo-induced polymerizations was established, their use in combination for block copolymer syntheses was investigated. With each alkoxyamine investigated, block copolymers were successfully obtained and the system was applied to the post-modification of polymer coatings for application in patterning and photografting.

Effects of strain artefacts arising from a pre-defined callus domain in models of bone healing mechanobiology

Iterative computational models have been used to investigate the regulation of bone fracture healing by local mechanical conditions. Although their predictions replicate some mechanical responses and histological features, they do not typically reproduce the predominantly radial hard callus growth pattern observed in larger mammals. We hypothesised that this discrepancy results from an artefact of the models’ initial geometry. Using axisymmetric finite element models, we demonstrated that pre-defining a field of soft tissue in which callus may develop introduces high deviatoric strains in the periosteal region adjacent to the fracture. These bone-inhibiting strains are not present when the initial soft tissue is confined to a thin periosteal layer. As observed in previous healing models, tissue differentiation algorithms regulated by deviatoric strain predicted hard callus forming remotely and growing towards the fracture. While dilatational strain regulation allowed early bone formation closer to the fracture, hard callus still formed initially over a broad area, rather than expanding over time. Modelling callus growth from a thin periosteal layer successfully predicted the initiation of hard callus growth close to the fracture site. However, these models were still susceptible to elevated deviatoric strains in the soft tissues at the edge of the hard callus. Our study highlights the importance of the initial soft tissue geometry used for finite element models of fracture healing. If this cannot be defined accurately, alternative mechanisms for the prediction of early callus development should be investigated.

Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy

AIM To assess the effects of eye rubbing on corneal thickness (CT) and intraocular pressure (IOP) measurements obtained 0-30min after habitual eye rubbing in symptomatic patients. METHODS Measurements of IOP and CT were obtained at five locations (central, temporal, superior, nasal and inferior) before, and every 5min for 30min interval after 30s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11 age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing (for IOP), and for each corneal location (for CT)] and comparison were then made between groups (allergic versus control) for differences in any observed effects. RESULTS Within groups, baseline mean IOPs in the allergic patient-group (14.2±3.0 mm Hg) and in the control group (13.1±1.9 mm Hg) were similar at all times, after eye rubbing (P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups (allergic versus control), the changes in IOP remained under 1 mm Hg at all times (P=0.2) after 30min of eye rubbing. Between 0 and 30min of CT measurements after eye rubbing, the mean central CT (CCT), inferior CT (ICT), superior CT (SCT), temporal CT (TCT) and nasal CT (NCT) did not vary significantly from baseline values in the control and allergic-subject groups (P>0.05, for both). Between both groups, changes in CT were similar at all locations (P>0.05) except for the TC which was minimally thinner by about 4.4 µm (P=0.001) in the allergic subjects than in the control subjects, 30min following 30s of eye rubbing. CONCLUSION IOP measured in allergic subjects after 30s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and 30min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it varied between +10 and -7.5 µm following eye rubbing, with the temporal cornea showing consistent reductions in thickness in the subjects with allergy. However, this reduction was minimal and was considered to not be clinically relevant.

Cell type-dependent, infection-induced, aberrant DNA methylation in gastric cancer

Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders. In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed. In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.

Experimental and numerical investigation of strain-rate dependent mechanical properties of single living cells

The objective of this project is to investigate the strain-rate dependent mechanical behaviour of single living cells using both experimental and numerical techniques. The results revealed that living cells behave as porohyperlastic materials and that both solid and fluid phases within the cells play important roles in their mechanical responses. The research reported in this thesis provides a better understanding of the mechanisms underlying the cellular responses to external mechanical loadings and of the process of mechanical signal transduction in living cells. It would help us to enhance knowledge of and insight into the role of mechanical forces in supporting tissue regeneration or degeneration.

An improved modal strain energy method for structural damage detection, 2D simulation

Structural damage detection using modal strain energy (MSE) is one of the most efficient and reliable structural health monitoring techniques. However, some of the existing MSE methods have been validated for special types of structures such as beams or steel truss bridges which demands improving the available methods. The purpose of this study is to improve an efficient modal strain energy method to detect and quantify the damage in complex structures at early stage of formation. In this paper, a modal strain energy method was mathematically developed and then numerically applied to a fixed-end beam and a three-story frame including single and multiple damage scenarios in absence and presence of up to five per cent noise. For each damage scenario, all mode shapes and natural frequencies of intact structures and the first five mode shapes of assumed damaged structures were obtained using STRAND7. The derived mode shapes of each intact and damaged structure at any damage scenario were then separately used in the improved formulation using MATLAB to detect the location and quantify the severity of damage as compared to those obtained from previous method. It was found that the improved method is more accurate, efficient and convergent than its predecessors. The outcomes of this study can be safely and inexpensively used for structural health monitoring to minimize the loss of lives and property by identifying the unforeseen structural damages.

Structural and electronic properties of layered arsenic and antimony arsenide

Layered materials exhibit intriguing electronic characteristics and the search for new types of two-dimensional (2D) structures is of importance for future device fabrication. Using state-of-art first principle calculations, we identify and characterize the structural and electronic properties of two 2D layered arsenic materials, namely, arsenic and its alloy AsSb. The stable 2D structural configuration of arsenic is confirmed to be the low-buckled two-dimensional hexagonal structure by phonon and binding energy calculations. The monolayer exhibits indirect semiconducting properties with gap around 1.5 eV (corrected to 2.2 eV by hybrid function), which can be modulated into a direct semiconductor within a small amount of tensile strain. These semiconducting properties are preserved when cutting into 1D nanoribbons, but the band gap is edge dependent. It is interesting to find that an indirect to direct gap transition can be achieved under strain modulation of the armchair ribbon. Essentially the same phenomena can be found in layered AsSb, except a weak Rashba induced band splitting is present in AsSb due to the nonsymmetric structure and spin orbit coupling. When an additional layer is added on the top, a semiconductor–metal transition will occur. The findings here broaden the family of 2D materials beyond graphene and transition metal dichalcogenides and provide useful information for experimental fabrication of new layered materials with possible application in optoelectronics.

Genome Sequence of Acinetobacter baumannii Strain A1, an Early Example of Antibiotic-Resistant Global Clone 1

Acinetobacter baumannii isolate A1 was recovered in the United Kingdom in 1982 and belongs to global clone 1 (GC1). Here, we present its complete 3.91-Mbp genome sequence, generated via a combination of short-read sequencing (Illumina), long-read sequencing (PacBio), and manual finishing.