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The supply of global information technology (IT) workers does not meet the demand of the industry. Therefore, researchers try to distill ways to increase and retain the IT talent pipeline. Ensuring that IT professionals remain in their IT careers is an essential element of such research. The influence of technostress on job turnover is evident. Yet, we know little about the impact of technostress on career turnaway and its interaction effects on the antecedents of turnaway intention. While job turnover may negatively impact a specific organization, career turnaway has negative implications for the industry. Losing IT professionals from the field means that additional efforts toward motivating, recruiting, educating, and preparing replacement talent are needed. By examining the dynamics of technostress on IT professionals' career turnaway intention (N=512), we reveal two critical findings. First, technostress reduces the IT professional's commitment to their IT career and increases exhaustion from their IT career experience. Second, technostress moderates IT professionals' commitment to their profession and career turnaway intentions. To remedy these concerns, we provide managerial advice and provide suggestions for future research.

The present study is focused on the thermal resisting characteristics of concrete. To impart the thermal resistivity, a fiber of Polypropylene (PP) has been added in to the desired concrete mix. The selected grade for the experimental study is M25 and M30. The test on compressive strength, thermal conductivity and thermal diffusivity were made for M25 and M30 concrete with and without inducing temperature. From the results, it is inferred that gain in temperature strength for PP fibre concrete is estimated as 6.3% and 3.1% for 7 days and 5.3% and 2.7% for 28 days against the conventional concrete for M25 and M30 respectively. By observing the thermal conductivity values, both M25 and M30 PP concrete performed well. But for thermal diffusivity values, M30 PP concrete is performed higher than M25 PP concrete.

Purpose: The purpose of this study was to examine the extent to which formal announcement of inflation targeting impacts on inflation and inflation volatility, from an emerging economy’s perspective. Methodology: Annual time series data from 1985 to 2014, which was sourced from the World Development Indicators (WDI) and the Bank of Ghana (BoG) was used. The data was interpolated into quarterly data using E-Views. The GARCH (1 1) and AR 2-Newey West Models were employed. Findings: The study found that the formal announcement of inflation targeting had a significant negative impact on inflation and its volatility. Thus, the study discovered that research works arguing that inflation targeting has no beneficial influence on inflation must take into account the type of economic structure at play, policy credibility, institutional efficiency, and the general public's responsiveness to institutional policies and information. Implications: This scholarly work would aid policy makers, academic institutions and the understanding of the general public in matters of inflation targeting. This paper concludes that the formal announcement of inflation targeting contributes greatly to stabilize both the inflation rate and inflation volatility, and that, countries that adopt a piloting-based adoption will not achieve the gains of the policy framework within the piloting period.

Multimorbid patients who enter English NHS hospitals are frequently subject to care pathways designed to assess, diagnose and treat single medical conditions. Opportunities are thereby lost to offer patients more holistic, person-centred care. Hospital organisations elsewhere are known to use in-hospital, multi-specialty, integrated clinical care (ICC) to overcome this problem. This perspective piece aims to critically discuss barriers to implementing this form of ICC in the English NHS focusing on six key areas: information technologies, the primary–secondary care interface, internal hospital processes, finance, workload, professional roles and behaviours. Integrated care programmes currently underway are largely focused on macro (system) and meso (organisational) levels. A micro (clinical) level ICC, offering highly coordinated multispecialty expertise to multimorbid hospital patients could fill an important gap in the current care pathways.

In many parts of the world, water scarcity is increasing due to climate change and the deterioration of the quantity and quality of water sources. In the southeastern U.S., water conservation is of particular concern because of the decades-long water war between the states of Florida, Georgia, and Alabama over two shared river basins. Individuals can only do so much to conserve water in their home, but different forms of donations can contribute to larger efforts resulting in greater environmental impact. Using a conceptual framework connecting self-identity to water conservation contribution engagement, the purpose of this study was to determine if personal water conservation behavioral intent impacted contributions to organizations supporting water conservation so effective communication strategies can be developed. Previous studies connected self-identity and intention to engage in pro-environmental behaviors, but there is a lack of research on the connection to water conservation donation behavior. Respondents were recruited to take an online survey using non-probability opt-in sampling. Self-reported intent to engage in water conservation behaviors, current contribution behaviors (if they donate to an organization that protects water, are a member of a water conservation organization, own a specialty license plate that supports water conservation, and volunteer for water conservation events), and total family income in the past year were obtained. Data were analyzed using point-biserial correlations and binary logistic regressions. The results indicated personal water conservation behavioral intent was positively correlated to water conservation contribution behaviors. Personal water conservation behavioral intent and income level were significant predictors of contribution behaviors. Environmental communicators and educators should encourage those who identify as conservationists to increase their self-identity through contributing to organizations. Future research should be conducted to determine if actual versus perceived discretionary income and/or time is a predictor of contributions.

An $(r,z,k)$-mixed graph $G$ has every vertex with undirected degree $r$, directed in- and out-degree $z$, and diameter $k$. In this paper, we study the case $r=z=1$, proposing some new constructions of $(1,1,k)$-mixed graphs with a large number of vertices $N$. Our study is based on computer techniques for small values of $k$ and the use of graphs on alphabets for general $k$. In the former case, the constructions are either Cayley or lift graphs. In the latter case, some infinite families of $(1,1,k)$-mixed graphs are proposed with diameter of the order of $2\log_2 N$.

Security is one of the major concerns while designing robust protocols for underwater sensor networks (UWSNs). The underwater sensor node (USN) is an example of medium access control (MAC) that should control underwater UWSN, and underwater vehicles (UV) combined. Therefore, our proposed method, in this research, investigates UWSN combined with UV optimized as an underwater vehicular wireless network (UVWSN) that can completely detect malicious node attacks (MNA) from the network. Thus, MNA that engages the USN channel and launches MNA is resolved by our proposed protocol through SDAA (secure data aggregation and authentication) protocol deployed in UVWSN. SDAA protocol plays a significant role in secure data communication, as the cluster-based network design (CBND) network organization creates a concise, stable, and energy-efficient network. This paper introduces SDAA optimized network known as UVWSN. In this proposed SDAA protocol, the cluster head (CH) is authenticated through the gateway (GW) and the base station (BS) to guarantee that a legitimate USN oversees all clusters deployed in the UVWSN are securely established for providing trustworthiness/privacy. Furthermore, the communicated data in the UVWSN network guarantee that data transmission is secure due to the optimized SDAA models in the network. Thus, the USNs deployed in the UVWSN are securely confirmed to maintain secure data communication in CBND for energy efficiency. The proposed method is implemented and validated on the UVWSN for measuring reliability, delay, and energy efficiency in the network. The proposed method is utilized for monitoring scenarios for inspecting vehicles or ship structures in the ocean. Based on the testing results, the proposed SDAA protocol methods improve energy efficiency and reduce network delay compared to other standard secure MAC methods.

Refractory epilepsy is the main neurological manifestation of Alpers’ syndrome, a severe childhood-onset mitochondrial disease caused by bi-allelic pathogenic variants in the mitochondrial DNA (mtDNA) polymerase gamma gene (POLG). The pathophysiological mechanisms underpinning neuronal hyperexcitabilty leading to seizures in Alpers’ syndrome remain unknown. However, pathological changes to reactive astrocytes are hypothesised to exacerbate neural dysfunction and seizure-associated cortical activity in POLG-related disease. Therefore, we sought to phenotypically characterise astrocytic pathology in Alpers’ syndrome. We performed a detailed quantitative investigation of reactive astrocytes in post-mortem neocortical tissues from thirteen patients with Alpers’ syndrome, eight neurologically normal controls and five sudden unexpected death in epilepsy (SUDEP) patients, to control for generalised epilepsy-associated astrocytic pathology. Immunohistochemistry to identify glial fibrillary acidic protein (GFAP)-reactive astrocytes revealed striking reactive astrogliosis localised to the primary visual cortex of Alpers’ syndrome tissues, characterised by abnormal-appearing hypertrophic astrocytes. Phenotypic characterisation of individual GFAP-reactive astrocytes demonstrated decreased abundance of mitochondrial oxidative phosphorylation (OXPHOS) proteins and altered expression of key astrocytic proteins including Kir4.1 (subunit of the inwardly rectifying K+ ion channel), AQP4 (astrocytic water channel) and glutamine synthetase (enzyme that metabolises glutamate). These phenotypic astrocytic changes were typically different from the pathology observed in SUDEP tissues, suggesting alternative mechanisms of astrocytic dysfunction between these epilepsies. Crucially, our findings provide further evidence of occipital lobe involvement in Alpers’ syndrome and support the involvement of reactive astrocytes in the pathogenesis of POLG-related disease.

This study investigates the influence of fibre orientation and heat flux on the post-fire (residual) load-bearing properties of carbon fibre-reinforced polymer (CFRP) laminates. As a result, a deep insight into the post-fire load-bearing response is gained, which is necessary to fully understand and assess the advantages of CFRP laminates containing different fibre orientations for use in load-bearing structures. Specimens were produced from three CFRP laminates containing different fibre orientations, exposed to varying heat fluxes up to 40?kW/m2$$ \mathrm{kW}/{\mathrm{m}}^2 $$ and then loaded in either tension or three-point bending at ambient room temperature. The study's results have shown that the post-fire behaviour of CFRP specimens is sensitive to changes in fibre orientation and heat flux. For example, specimens with an anisotropic fibre orientation in tension had the highest tensile load-bearing capacity, whereas those with bidirectional and multi-directional fibre orientations demonstrated lower tensile load-bearing capacities. In bending, however, specimens containing bidirectional and multidirectional fibre orientations had higher load-bearing capacities than specimens with an anisotropic fibre orientation. Furthermore, the data also shows that exposure to a heat flux reduces the load-bearing capacity in both the bending and tensile specimens.

Background: To establish national prevalence of child maltreatment, reliable, valid and contextually appropriate measurement is needed. This paper outlines the refinement, adaptation and testing of child maltreatment sections of the Juvenile Victimization Questionnaire (JVQ)-R2 for use in the Australian context.Methods: Three phases were undertaken: 1) Conceptual analysis of the five forms of child maltreatment (physical abuse, sexual abuse, emotional or psychological abuse, neglect, and experience of domestic violence), item mapping and review, item development, and independent expert review; 2) Cognitive testing with members of the general population, and individuals who have experienced maltreatment; and 3) Pilot testing and quantitative psychometric assessment with a random sample of Australians aged 16–65+ years.Results: The final measure included a total of 17 child maltreatment screener items, assessing Physical Abuse (2 items), Sexual abuse (5 items (including 2 non-contact items and 3 contact items), Emotional Abuse (3 items), Neglect (3 items), and Experience of Domestic Violence (4 items). Screener items were also included on corporal punishment (1 item), and internet sexual victimization (2 items). The final 17-item revised JVQ had high face and conceptual validity and good internal reliability (α = 0.86 and Ω = 0.87). Test re-test reliability was moderate to high for individual screeners ranging from k = 0.45 to 0.89.Conclusions: Results indicate the Juvenile Victimization Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study) is a suitable instrument for assessing population-wide prevalence of maltreatment. It is congruent with conceptual models of maltreatment and shows good reliability and validity in this Australian sample.

Objective: Traumatic spinal cord injury (SCI) causes an initial injury followed by a protracted phase of spinal cord tissue hypoxia. This tissue hypoxia contributes to secondary injury, leading to worse motor and cardio-autonomic outcomes in the chronic setting. No neuroprotective agents to mitigate secondary injury have been identified as efficacious in clinical trials. However, we have demonstrated that taking a cardio-centric approach to hemodynamic management following SCI by augmenting cardiac output and mean arterial pressure (MAP) with the b1-adrenoceptor agonist dobutamine (DOB), and further coupling DOB infusion with the inhalation of ethyl nitrite (ENO), an S-nitrosylating agent, is associated with improved spinal cord oxygenation in the acute phase post-SCI. Aim: To determine the influence of a cardio-centric approach to hemodynamic management with adjuvant ENO inhalation following SCI on long term outcomes. We hypothesized that treatment with DOB and ENO in the acute phase following SCI would mitigate secondary injury and improve cardiovascular outcomes in the chronic setting. Methods. A total of 34 male Wistar rats underwent a T3 contusion injury (300 kdyn) and were assigned into 4 treatment groups: control (n=6), ENO (n=6), DOB (n=12), and combined DOB and ENO (n=10). At 11-weeks post-SCI, a locomotor assessment was conducted using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. At 12-weeks post-SCI, rodents were anesthetized with intravenous urethane (2.44±0.50 g/kg) and instrumented with a solid-state pressure transducer in the carotid artery to measure MAP. Results. We observed a higher MAP in both DOB (113.6 ± 11.4 mmHg; p = 0.030) and ENO+DOB (116.7 ± 14.6 mmHg; p=0.013) treated groups when compared with controls (94.65 ± 11.62 mmHg). The MAP of ENO treated animals (91.6 ± 7.3 mmHg; P= 0.97) was not different from controls. No differences in BBB scores were found between DOB (15.17 ± 4.49), ENO+DOB (13.95 ± 3.86), ENO (12.5 ± 2.5) and control (11.8 ± 2.7)(P=0.29). Collectively, these data suggest that DOB treatment, alone or in combination with ENO, improves systemic hemodynamics in the chronic high-thoracic SCI setting US Department of Defense, ICORD Seed Grant, Craig H. Neilsen Foundation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Objective: High-thoracic spinal cord injury (SCI) is associated with blood pressure (BP) dysregulation that consists of persistent hypotension, orthostatic intolerance and autonomic dysreflexia. Whilst several mechanisms have been suggested to underlie blood pressure dysregulation post-SCI, the most common inference made is that the sub-lesional sympathetic circuitry is hypoactive due to a loss of medullary input to the sympathetic preganglionic neurons. Yet, a remarkable paucity of data exists from electrophysiological studies that have assessed sympathetic nerve activity (SNA) in the setting of SCI. Aim: Assess the changes in SNA and resting BP in rats with and without high-thoracic SCI. Methods: 24 male Wistar rats (10wks old) were randomized and counterbalanced to receive a severe contusion SCI at the T3 spinal level (n=12) or remain as naïve controls (CON). Two weeks post-SCI, rats underwent our neurovascular terminal preparation. Animals were ventilated, anesthetized with inhalant isoflurane, and underwent catheterization of the left-femoral artery (BP), as well as the right femoral artery and vein for arterial blood gas sampling and i.v. fluid/drugs, respectively. Rats were then transitioned to urethane anesthesia (~2.1g.kg-1 i.v). Next, the splanchnic nerve was isolated from a retroperitoneal approach, cut, and the proximal end was recorded using a suction electrode for the measurement of splanchnic sympathetic nerve activity (sSNA). Following 30 minutes of hemodynamic stabilization, SNA and cardiovascular hemodynamics were sampled for 10 minutes, from which a 1 min recording was selected for analyses. Animals were subsequently administered a hexamethonium bolus (30 mg.kg-1) to block ganglionic transmission and the euthanized with chloral hydrate. Results: SCI animals exhibited lower systolic, diastolic and mean arterial BP (all p-1, p=0.038) as well reduced burst height (2.2 ± 1.5 vs. 3.7 ± 0.8 v.s-1, p=0.033), but the number of sSNA spikes.s-1 was higher in SCI vs. CON (182 ± 65 vs. 155 ± 33, p=0.043). Blood gases were stable and similar between groups. Conclusions: Our findings show that persistent hypotension in SCI animals is associated with lower total sub-lesional sSNA. While SCI resulted in more spontaneous sSNA spikes, these spikes fail to coordinate into equally-sized sSNA bursts. International Spinal Research Trust and Natural Sciences and Engineering Research Council of Canada (NSERC). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Context Hyperaccumulator plants are of considerable interest for their extreme physiology. Stackhousia tryonii is a nickel (Ni) hyperaccumulator plant endemic to ultramafic outcrops in Queensland (Australia) capable of attaining up to 41 300 μg g−1 foliar Ni. Aims This study sought to elucidate the distribution of Ni in S. tryonii by using synchrotron X-ray fluorescence micro-computed tomography (XFM-CT), complemented with elemental maps acquired from physically sectioned plant organs. Its Ni-enriched cylindrical photosynthetic stems make them particularly well suited samples for synchrotron XFM-CT. Methods XFM-CT enables ‘virtual sectioning’ of a sample, avoiding artefacts arising from physical sample preparation. The method can be used on fresh samples that are frozen during the analysis, which preserves ‘life-like’ conditions by limiting radiation damage. It also prevents/minimises other artefacts. Key results The results showed that Ni is mainly concentrated in the apoplastic space surrounding epidermal cells, and in some epidermal cell vacuoles. This finding is significant because this ‘free’ solute Ni is likely to be lost during physical sectioning. Conclusions and implications This case study has highlighted the utility of the XFM-CT approach for visualising metals within intact plant organs, which may be used across the plant sciences.

ContextForest restoration plays an important role in global efforts to slow biodiversity loss and mitigate climate change. Vegetation in remnant forests can form striking patterns that relate to ecological processes, but restoration targets tend to overlook spatial pattern. While observations of intact reference ecosystems can help to inform restoration targets, field surveys are ill-equipped to map and quantify spatial pattern at a range of scales, and new approaches are needed.ObjectiveThis review sought to explore practical options for creating landscape-scale forest restoration targets that embrace spatial pattern.MethodsWe assessed how hierarchy theory, satellite remote sensing, landscape pattern analysis, drone-based remote sensing and spatial point pattern analysis could be applied to assess the spatial pattern of reference landscapes and inform forest restoration targets.ResultsHierarchy theory provides an intuitive framework for stratifying landscapes as nested hierarchies of sub-catchments, forest patches and stands of trees. Several publicly available tools can map patches within landscapes, and landscape pattern analysis can be applied to quantify the spatial pattern of these patches. Drones can collect point clouds and orthomosaics at the stand scale, a plethora of software can create maps of individual trees, and spatial point pattern analysis can be applied to quantify the spatial pattern of mapped trees.ConclusionsThis review explored several practical options for producing landscape scale forest restoration targets that embrace spatial pattern. With the decade on ecosystem restoration underway, there is a pressing need to refine and operationalise these ideas.

We develop a logic-based approach for designing simulation-based training scenarios. Our methodology embodies a concise definition of the scenario concept and integrates the notions of training goals, acceptable versus unacceptable actions and performance scoring. The approach applies classical artificial intelligence (AI) planning to extract coherent plays from a causal description of the training domain. The domain- and task-specific parts are defined in a high-level action description language [Formula: see text]. Generic causal and temporal logic is added when the causal theory is compiled into the underlying Answer Set Programming (ASP) language. The ASP representation is used to derive a scoring function that reflects the quality of a play or training session, based on a distinction of states and actions into green (acceptable) and red (unacceptable) ones. To that end, we add to the casual theory a set of norms that specify an initial assignment of colors. The ASP engine uses these norms as axioms and propagates colors by consulting the causal theory. We prove that any set of such norms constitutes a conservative extension of the underlying causal theory. With this work, we hope to lay the foundation for the development of design and analysis tools for exercise managers. We envision a software system that lets an exercise manager view all plays of a tentative scenario design, with expediency information and scores for each possible play. Our approach is applicable to any domain in which means-ends reasoning is pertinent. We illustrate the approach in the domain of crisis response and management.

Two Eulerian circuits, both starting and ending at the same vertex, are avoiding if at every other point of the circuits they are at least distance 2 apart. An Eulerian graph which admits two such avoiding circuits starting from any vertex is said to be doubly Eulerian. The motivation for this definition is that the extremal Eulerian graphs, i.e. the complete graphs on an odd number of vertices and the cycles, are not doubly Eulerian. We prove results about doubly Eulerian graphs and identify those that are the `densest' and `sparsest' in terms of the number of edges., 22 pages; 9 figures

Objectives To estimate the prevalence in Australia of each type of child maltreatment; to identify gender- and age group-related differences in prevalence. Design, setting Cross-sectional national survey; mobile telephone interviews using random digit dialling (computer-generated), Australia, 9 April – 11 October 2021. Retrospective self-report data using validated questionnaire (Juvenile Victimisation Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study). Participants People aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16–24 years and 1000 respondents each from five further age groups (25–34, 35–44, 45–54, 55–64, 65 years or more). Main outcome measures Proportions of respondents reporting physical abuse, sexual abuse, emotional abuse, neglect, and exposure to domestic violence to age 18 years, assessed with the Juvenile Victimization Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study), overall and by gender and age group, and weighted to reflect characteristics of the Australian population aged 16 years or more in 2016. Results Complete survey data were available for 8503 eligible participants (14% response rate). Physical abuse was reported by 32.0% of respondents (95% confidence interval [CI], 30.7–33.3%), sexual abuse by 28.5% (95% CI, 27.3–29.8%), emotional abuse by 30.9% (95% CI, 29.7–32.2%), neglect by 8.9% (95% CI, 8.1–9.7%), and exposure to domestic violence by 39.6% (95% CI, 38.3–40.9%). The proportions of respondents who reported sexual abuse, emotional abuse, or neglect were each statistically significantly larger for women than men. The reported prevalence of physical abuse by respondents aged 16–24 years was lower than for those aged 25–34 years, and that of sexual abuse was lower than for those aged 35–44 years, suggesting recent declines in the prevalence of these maltreatment types. Conclusions Child maltreatment is common in Australia, and larger proportions of women than men report having experienced sexual abuse, emotional abuse, and neglect during childhood. As physical and sexual abuse may have declined recently, public health policy and practice may have positive effects, justifying continued monitoring and prevention activities.

Objectives To examine associations between child maltreatment and health service use, both overall, by type and by the number of types of maltreatment reported. Design, setting Cross-sectional, retrospective survey using the Juvenile Victimization Questionnaire-R2: Adapted Version (Australian Child Maltreatment Study); computer-assisted mobile telephone interviews using random digit dialling, Australia, 9 April – 11 October 2021. Participants Australians aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16–24 years and 1000 respondents each from the five age groups (25–34, 35–44, 45–54, 55–64, 65 years or more). Main outcome measures Self-reported health service use during the past twelve months: hospital admissions, length of stay, and reasons for admission; and numbers of consultations with health care professionals, overall and by type. Associations between maltreatment and health service use are reported as odds ratios adjusted for age group, gender, socio-economic status, financial hardship (childhood and current), and geographic remoteness. Results A total of 8503 participants completed the survey. Respondents who had experienced child maltreatment were significantly more likely than those who had not to report a hospital admission during the preceding twelve months (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.16–1.66), particularly admission with a mental disorder (aOR, 2.4; 95% CI, 1.03–5.6). The likelihood of six or more visits to general practitioners (aOR, 2.37; 95% CI, 1.87–3.02) or of a consultation with a mental health nurse (aOR, 2.67; 95% CI, 1.75–4.06), psychologist (aOR, 2.40; 95% CI, 2.00–2.88), or psychiatrist (aOR, 3.02; 95% CI, 2.25–4.04) were each higher for people who reported maltreatment during childhood. People who reported three or more maltreatment types were generally most likely to report greater health service use. Conclusions Child maltreatment has a major impact on health service use. Early, targeted interventions are vital, not only for supporting children directly, but also for their longer term wellbeing and reducing their health system use throughout life.

Objectives To describe the aims, design, methodology, and respondent sample representativeness of the Australian Child Maltreatment Study (ACMS). Design, setting Cross-sectional, retrospective survey; computer-assisted mobile telephone interviewing using random digit dialling (computer-generated), Australia, 9 April – 11 October 2021. Participants People aged 16 years or more. The target sample size was 8500 respondents: 3500 people aged 16–24 years and 1000 respondents each from five further age groups (25–34, 35–44, 45–54, 55–64, 65 years or more). Main outcome measures Primary outcomes: Emotional abuse, neglect, physical abuse, sexual abuse, exposure to domestic violence during childhood, assessed with the Juvenile Victimization Questionnaire-R2 Adapted Version (Australian Child Maltreatment Study). Secondary outcomes: selected mental disorder diagnoses (Mini International Neuropsychiatric Interview, MINI), selected physical health conditions, health risk behaviours, health service use. Results The demographic characteristics of the ACMS sample were similar to those of the Australian population in 2016 with respect to gender, Indigenous status, region and remoteness category of residence, and marital status, but larger proportions of participants were born in Australia, lived in areas of higher socio-economic status, had tertiary qualifications, and had income greater than $1250 per week. Population weights were derived to adjust for these differences. Associations between the number of calls required to recruit participants and maltreatment rates and health outcomes were not statistically significant. Conclusions The ACMS provides the first reliable estimates of the prevalence of each type of child maltreatment in Australia. These estimates, and those of associated mental health and health risk behaviours reported in this supplement can inform policy and practice initiatives for reducing the prevalence of child maltreatment and its consequences. Our benchmark study also provides baseline data for repeated waves of the ACMS that will assess the effectiveness of these initiatives.

Supplementary Figure S1 describes the pre-existing antibody responses to tumor antigens in patients with surgically resected HER2+ breast cancer. Supplementary Figure S2 compares the proportion of either the metastatic or adjuvant patients that respond to therapy with increased antibody responses. Table S1 shows the demographic information for the patients in this study. Table S2 compares the levels of antibodies to tumor antigens and TT in metastatic patients and healthy controls. Table S3 compares the mean pre- and post-treatment antibody levels to all of the tumor antigens and TT in the patients with metastatic disease. Table S4 describes correlations of the antibody responses to the type of chemotherapy received in the metastatic patients. Table S5 shows the results of a cox univariate analysis correlating PFS and antibody responses. Table S6 shows the results of a cox univariate analysis correlating OS and antibody responses. Table S7 compares the mean pre- and post-treatment antibody levels to all of the tumor antigens and TT in patients with surgically-resected disease.

Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients.Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later.Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months.Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype. Clin Cancer Res; 24(13); 3014–25. ©2018 AACR.

Supplementary Figures S1-S6.

Background: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN).Methods: Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months.Results: Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC.Conclusions: SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival.Impact: SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC. Cancer Epidemiol Biomarkers Prev; 22(10); 1730–5. ©2013 AACR.

The addition of trastuzumab to chemotherapy extends survival among patients with HER2+ breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2+ breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2+ patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702–10. ©2016 AACR.

PDF - 93K, Receiver-operator curve for SLPI in early stage EOC versus control patients (A) and advanced stage EOC versus control patients (B).

PDF - 118K, Scatter plot comparing CA-125 concentrations and SLPI concentrations in control, early EOC, and advanced EOC patients. The dashed line shows the institutional upper limit of normal for CA-125 (35 units/ml).

Figure S1: Vaccination generates T cell immunity to FR following immunization.

Purpose: Despite their preclinical promise, previous MEK inhibitors have shown little benefit for patients. This likely reflects the narrow therapeutic window for MEK inhibitors due to the essential role of the P42/44 MAPK pathway in many nontumor tissues. GSK1120212 is a potent and selective allosteric inhibitor of the MEK1 and MEK2 (MEK1/2) enzymes with promising antitumor activity in a phase I clinical trial (ASCO 2010). Our studies characterize GSK1120212' enzymatic, cellular, and in vivo activities, describing its unusually long circulating half-life.Experimental Design: Enzymatic studies were conducted to determine GSK1120212 inhibition of recombinant MEK, following or preceding RAF kinase activation. Cellular studies examined GSK1120212 inhibition of ERK1 and 2 phosphorylation (p-ERK1/2) as well as MEK1/2 phosphorylation and activation. Further studies explored the sensitivity of cancer cell lines, and drug pharmacokinetics and efficacy in multiple tumor xenograft models.Results: In enzymatic and cellular studies, GSK1120212 inhibits MEK1/2 kinase activity and prevents Raf-dependent MEK phosphorylation (S217 for MEK1), producing prolonged p-ERK1/2 inhibition. Potent cell growth inhibition was evident in most tumor lines with mutant BRAF or Ras. In xenografted tumor models, GSK1120212 orally dosed once daily had a long circulating half-life and sustained suppression of p-ERK1/2 for more than 24 hours; GSK1120212 also reduced tumor Ki67, increased p27Kip1/CDKN1B, and caused tumor growth inhibition in multiple tumor models. The largest antitumor effect was among tumors harboring mutant BRAF or Ras.Conclusions: GSK1120212 combines high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors. Clin Cancer Res; 17(5); 989–1000. ©2011 AACR.

Supplementary Tables 1-3 from Distinct Concentration-Dependent Effects of the Polo-like Kinase 1–Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis

Supplementary Figure Legends 1-4 from Distinct Concentration-Dependent Effects of the Polo-like Kinase 1–Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis

Supplementary Figures 1-4 from Distinct Concentration-Dependent Effects of the Polo-like Kinase 1–Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis

Additions to Supplement Table 3 from Distinct Concentration-Dependent Effects of the Polo-like Kinase 1–Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis

Background Insecticide-treated nets (ITN) are the cornerstone of modern malaria vector control, with nearly 3 billion ITNs delivered to households in endemic areas since 2000. ITN access, i.e. availability within the household, based on the number of ITNs and number of household members, is a pre-requisite for ITN use. Factors determining ITN use are frequently examined in published literature, but to date, large household survey data on reasons given for non-use of nets have not been explored. Methods A total of 156 DHS, MIS, and MICS surveys conducted between 2003 and 2021 were reviewed for questions on reasons why nets were not used the previous night, identifying twenty-seven surveys. The percent of nets that were reported used the previous night was calculated for the 156 surveys, and frequencies and proportions of reasons for non-use were calculated within the twenty-seven surveys. Results were stratified by household supply of ITNs in three categories (not enough”, “enough”, and “more than enough”) and by residence (urban/rural). Results The proportion of nets used the previous night averaged over 70% between 2003 and 2021, with no discernible change over this period. Reported reasons for why a net goes unused fell largely into three categories—nets that are extra/being saved for future use; the perception that there is little risk of malaria (particularly in dry season); and “other” responses. Net attributes such as colour, size, shape, and texture, and concerns related to chemicals were the least frequent reasons given. Reasons for non-use of nets varied by household net supply, and in some surveys by residence. In Senegal’s continuous DHS, the proportion of nets used peaked during high transmission season, and the proportion of nets that went unused due to “no/few mosquitoes” peaked during the dry season. Conclusions Unused nets were primarily those being saved for later use, or were not used due to perceived low risk of malaria. Classifying reasons for non-use into broader categories facilitates the design of appropriate social and behaviour change interventions to address the major underlying reasons for non-use, where this is feasible.

During the COVID-19 pandemic, women and girls across the globe faced increased reliance on the digital space to access education, social support, and health and gender-based violence (GBV) services. While research from the last three years has explored how women and girls navigated and responded to their new virtual reality, minimal evidence has been generated from low-resource settings where access to technology may be limited. Further, no studies to date have examined these dynamics in Iraq, where women and girls already face numerous threats to safety due to various forms of structural violence and patriarchal family structures. This qualitative study aimed to examine women and girls’ experiences in the digital space during COVID-19 in Iraq, including the benefits and risks of engagement as well as how access to the digital space was controlled. Data for the present analysis come from the authors’ larger multi-country study investigating women and girls’ safety and access to GBV services in the context of the COVID-19 pandemic and related public health measures employed to control the spread of the virus. In Iraq, semi-structured key informant interviews were conducted virtually with fifteen GBV service providers. Following the translation and transcription of interviews, the thematic analysis highlighted several benefits and challenges women and girls experienced as they tried to access and utilize technology for schooling, support services, and obtaining and spreading information. While many women and girls increasingly and successfully relied on social media to spread awareness of GBV cases, key informants noted that women and girls also faced increased risks of experiencing electronic blackmail. In addition to a substantial digital divide in this context—which manifested as differential access to technology by gender, rural/urban status, and socioeconomic status—intrahousehold control of girls’ access to and use of technology left many adolescent girls unable to continue schooling and contributed to their further marginalization and consequent decline in well-being. Implications for women’s safety and mitigation strategies are also discussed.

Background and aims The pasture legume Trifolium subterraneum ssp. yanninicum exhibits waterlogging tolerance. This study investigates diversity for waterlogging tolerance within ssp. yanninicum. We tested the hypotheses that (1) variation for waterlogging tolerance exists within ssp. yanninicum and (2) is related to phenotypic and growth trait differences, which (3) reflect eco-geographic variables at site of origin. Methods Twenty-eight diverse ssp. yanninicum ecotypes collected from the Mediterranean region and four cultivars were grown in a controlled environment glasshouse. Seedling traits were measured at 14 and 21 days after sowing. Waterlogged and free-draining (control) treatments were then imposed for 28 days. Relative distance and multivariate plasticity indices were calculated. Results Under waterlogging, shoot (87–108% of controls) and root (80–116% of controls) relative growth rates (RGRs) differed significantly among ssp. yanninicum. Waterlogging tolerance, as assessed by shoot RGR, had strong positive correlations with root RGR (r = 0.86; P r = 0.59; P r = 0.55; P Conclusions Wide variation in waterlogging tolerance exists within ssp. yanninicum. Petiole length reduction, an easy-to-measure and non-destructive indicator, could be used as a preliminary selection tool when screening large numbers of ssp. yanninicum for waterlogging tolerance in a breeding program.

Purchasing through e-commerce continues to expand rapidly and is expected to reach $18.89 trillion by 2027. After two decades of e-commerce research, little is known about the effects of economic conditions (developed vs. developing). We synthesize prior e-purchase intention literature from multiple business disciplines (e.g., information systems, marketing) through a meta-analysis and use economic condition as an environmental moderator to explore this gap. We discuss the consolidated effects of the antecedents of e-purchase intention and explore research trends. We reveal that trust is the most studied antecedent, economic conditions of countries moderate some of the antecedents, and that this important research stream continues to evolve.

Reproductive phenology is well known to be a key feature of crop adaptation to diverse ecogeographic variation and management practices. Lentil is one of the founder pulse crops of middle-eastern Neolithic agriculture, and the modern-day domesticated lentil germplasm is generally considered to form three broad adaptation groups: Mediterranean, South Asian and northern temperate, which correspond approximately to the major global production environments. Understanding the molecular basis of these adaptations is crucial to maximise efficiency of breeding programs. Here, we use a QTL approach to dissect the earliness that is characteristic of the South Asian pilosae ecotype, and that suits it to the typically short winter cropping season. We identified two loci, DTF6a and DTF6b, at which dominant alleles confer early flowering. We show that, although these loci can interact in an additive manner, DTF6a alone is sufficient to confer early flowering even in extremely short photoperiods. Comparisons with closely related legume species confirmed the presence of a conserved cluster of three FT orthologs among potential candidate genes in the region, and expression analysis in near-isogenic material showed that the early dtf6a allele is associated with a strong derepression of the FTa1 gene in particular. Analysis of sequence variation revealed the presence of a 7.4 kb deletion in the FTa1-FTa2 intergenic region in the pilosae parent, and a wide survey of over 400 accessions with diverse origin showed that the dtf6a allele is dominant in South Asia material. Collectively, these results contribute to understanding the molecular basis of global adaptation in lentil, and further emphasize the importance of this conserved genomic region for adaptation in temperate legumes generally.