Modelling of Tirapazamine effects on solid tumour morphology

Bioreductive drugs are in clinical practice to exploit the resistance from tumour microenvironments especially in the hypoxic region of tumour. We pre-sented a tumour treatment model to capture the pharmacology of one of the most prominent bioreductive drugs, Tirapazamine (TPZ) which is in clinical trials I and II. We calculated solid tumour mass in our previous work and then integrated that model with TPZ infusion. We calculated TPZ cytotoxicity, concentration, penetra-tion with increasing distance from blood vessel and offered resistance from micro-environments for drug penetration inside the tumour while considering each cell as an individual entity. The impact of these factors on tumour morphology is also showed to see the drug behaviour inside animals/humans tumours. We maintained the heterogeneity factors in presented model as observed in real tumour mass es-pecially in terms of cells proliferation, cell movement, extracellular matrix (ECM) interaction, and the gradients of partial oxygen pressure (pO2) inside tumour cells during the whole growth and treatment activity. The results suggest that TPZ high concentration in combination with chemotherapy should be given to get maximum abnormal cell killing. This model can be a good choice for oncologists and re-searchers to explore more about TPZ action inside solid tumour

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

Operation of an optoelectronic crossbar switch containing a terabit-per-second free-space optical interconnect

The experimental operation of a terabit-per-second scale optoelectronic connection to a silicon very-large-scale-integrated circuit is described. A demonstrator system, in the form of an optoelectronic crossbar switch, has been constructed as a technology test bed. The assembly and testing of the components making up the system, including a flip-chipped InGaAs-GaAs optical interface chip, are reported. Using optical inputs to the electronic switching chip, single-channel routing of data through the system at the design rate of 250 Mb/s (without internal fan-out) was achieved. With 4000 optical inputs, this corresponds to a potential aggregate data input of a terabit per second into the single 14.6 /spl times/ 15.6 mm CMOS chip. In addition 50-Mb/s data rates were switched utilizing the full internal optical fan-out included in the system to complete the required connectivity. This simultaneous input of data across the chip corresponds to an aggregate data input of 0.2 Tb/s. The experimental system also utilized optical distribution of clock signals across the CMOS chip

Selective outcome reporting in trials of behavioural health interventions in health psychology and behavioural medicine journals: a review

Selective outcome reporting can result in overestimation of treatment effects, research waste, and reduced openness and transparency. This review aimed to examine selective outcome reporting in trials of behavioural health interventions and determine potential outcome reporting bias. A review of nine health psychology and behavioural medicine journals was conducted to identify randomised controlled trials of behavioural health interventions published since 2019. Discrepancies in outcome reporting were observed in 90% of the 29 trials with corresponding registrations/protocols. Discrepancies included 72% of trials omitting prespecified outcomes; 55% of trials introduced new outcomes. Thirty-eight percent of trials omitted prespecified and introduced new outcomes. Three trials (10%) downgraded primary outcomes in registrations/protocols to secondary outcomes in final reports; downgraded outcomes were not statistically significant in two trials. Five trials (17%) upgraded secondary outcomes to primary outcomes; upgraded outcomes were statistically significant in all trials. In final reports, three trials (7%) omitted outcomes from the methods section; three trials (7%) introduced new outcomes in results that were not in the methods. These findings indicate that selective outcome reporting is a problem in behavioural health intervention trials. Journal- and trialist-level approaches are needed to minimise selective outcome reporting in health psychology and behavioural medicine

Defect-mediated ferromagnetism in ZnO:Mn nanorods

In this work, the structural, chemical and magnetic properties of ZnO:Mn nanorods were investigated. Firstly, well-aligned ZnO nanorods with their long axis parallel to the crystalline c-axis were successfully grown by the vapor phase transport technique on Si substrates coated with a ZnO buffer layer. Mn metal was then diffused into these nanorods at different temperatures in vacuum. From SEM results, ZnO:Mn nanorods were observed to have diameters of ~100 nm and lengths of 4 µm. XPS analysis showed that the Mn dopant substituted into the ZnO matrix with a valence state of +2. Magnetic measurements performed at room temperature revealed that undoped ZnO nanorods exhibit ferromagnetic behavior which may be related to oxygen vacancy defect-mediated d0 ferromagnetism. ZnO:Mn samples were seen to show an excess room temperature ferromagnetism that is attributed to the presence of oxygen vacancy defects forming bound magnetic polarons involving Mn

Cohort profile: the Australian genetics of depression study

PURPOSE:Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. PARTICIPANTS:A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail. FINDINGS TO DATE:95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed. FUTURE PLANS:A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.Enda M Byrne, Katherine M Kirk, Sarah E Medland, John J McGrath, Lucia Colodro-Conde, Richard Parker ... et al