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Purpose: This study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model. Methods: One hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen's kappa statistic. Results: Twenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96–7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23–11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen's k = 0.31). Conclusion: RECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015. [ABSTRACT FROM AUTHOR]

Background: Oncology patients have had to make many changes to minimise their exposure to COVID-19, causing stress. Despite education, some patients still do not recognise potential COVID symptoms. Aims: We assessed patient knowledge of COVID, and its impact on their behaviours, concerns, and healthcare experience. Methods: A 16-page questionnaire was distributed to 120 oncology patients attending the day unit of a tertiary Irish cancer centre for systemic anti-cancer therapy (May/June 2020). The Irish 7-day COVID incidence during this period ranged from 2 to 11 cases/100,000 people. Results: One hundred and one responses were received, 1% had tested positive for COVID, and 31% had undergone testing. Participant insight into their knowledge about COVID and their own behaviour was limited in some cases. Seventy-five percent reported total compliance with restrictions, but many were not fully compliant. Self-reported confidence in knowledge was high, but did not predict demonstrated knowledge. Sixty percent did not recognise two or more symptoms; 40% did not self-identify as high-risk. Patients reported more health-related worry (72%), loneliness (51%), and lower mood (42%) since the pandemic began. Financial toxicity worsened, with increased financial worry (78%), reductions in household income (40%), and increased costs due to lockdown (62%). Use of facemasks introduced new communications barriers for 67% of those with hearing loss. Conclusions: Despite self-reported confidence in knowledge, some patient's recognition of COVID symptoms and the preventative strategies they should use are not optimal, highlighting the need for further education in this regard. COVID has been a significant stressor for patients and more practical, financial, and psychological supports are needed. [ABSTRACT FROM AUTHOR]

This study examines the effects of a COVID-19 outbreak on levels of social capital on a college campus, drawing on survey data collected from students at two colleges—one that experienced an outbreak and one that did not. Social capital is examined as an individual level resource and as a campus level normative tool used to fight collective action problems. We test the hypothesis that the outbreak, as a "shock" to the campus, diminished social capital. We also test hypotheses on gender, race, and ethnicity and social capital, informed by prior research. Our findings suggest that the outbreak did reduce social capital at both the individual and campus levels, though individual social capital had a mitigating effect that increased campus social capital. We find also that gender was significantly linked to campus social capital, while race was predictive of individual level social capital. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic forced many surgeons to adopt "virtual medicine" practices, defined as telehealth services for patient care and online platforms for continuing medical education. The purpose of this study was to assess spine surgeon reliance on virtual medicine during the pandemic and to discuss the future of virtual medicine in spine surgery.Methods: A comprehensive survey addressing demographic data and virtual medicine practices was distributed to spine surgeons worldwide between March 27, 2020, and April 4, 2020.Results: 902 spine surgeons representing seven global regions responded. 35.6% of surgeons were identified as "high telehealth users," conducting more than half of clinic visits virtually. Predictors of high telehealth utilization included working in an academic practice (OR = 1.68, p = 0.0015) and practicing in Europe/North America (OR 3.42, p < 0.0001). 80.1% of all surgeons were interested in online education. Dedicating more than 25% of one's practice to teaching (OR = 1.89, p = 0.037) predicted increased interest in online education. 26.2% of respondents were identified as "virtual medicine surgeons," defined as surgeons with both high telehealth usage and increased interest in online education. Living in Europe/North America and practicing in an academic practice increased odds of being a virtual medicine surgeon by 2.28 (p = 0.002) and 1.15 (p = 0.0082), respectively. 93.8% of surgeons reported interest in a centralized platform facilitating surgeon-to-surgeon communication.Conclusion: COVID-19 has changed spine surgery by triggering rapid adoption of virtual medicine practices. The demonstrated global interest in virtual medicine suggests that it may become part of the "new normal" for surgeons in the post-pandemic era. [ABSTRACT FROM AUTHOR]

Purpose: To utilize a global survey to elucidate spine surgeons' perspectives towards research and resident education within telemedicine. Methods: A cross-sectional, anonymous email survey was circulated to the members of AO Spine, an international organization consisting of spine surgeons from around the world. Questions were selected and revised using a Delphi approach. A major portion of the final survey queried participants on experiences with telemedicine in training, the utility of telemedicine for research, and the efficacy of telemedicine as a teaching tool. Responses were compared by region. Results: A total of 485 surgeons completed the survey between May 15, 2020 and May 31, 2020. Though most work regularly with trainees (83.3%) and 81.8% agreed that telemedicine should be incorporated into clinical education, 61.7% of respondents stated that trainees are not present during telemedicine visits. With regards to the types of clinical education that telemedicine could provide, only 33.9% of respondents agreed that interpretation of physical exam maneuvers can be taught (mean score = − 0.28, SD = ± 1.13). The most frequent research tasks performed over telehealth were follow-up of imaging (28.7%) and study group meetings (26.6%). Of all survey responses provided by members, there were no regional differences (p > 0.05 for all comparisons). Conclusions: Our study of spine surgeons worldwide noted high agreement among specialists for the implantation of telemedicine in trainee curricula, underscoring the global acceptance of this medium for patient management going forward. A greater emphasis towards trainee participation as well as establishing best practices in telemedicine are essential to equip future spine specialists with the necessary skills for navigating this emerging platform. [ABSTRACT FROM AUTHOR]

Introduction: While telemedicine usage has increased due to the COVID-19 pandemic, there remains little consensus about how spine surgeons perceive virtual care. The purpose of this study was to explore international perspectives of spine providers on the challenges and benefits of telemedicine.Methods: Responses from 485 members of AO Spine were analyzed, covering provider perceptions of the challenges and benefits of telemedicine. All questions were optional, and blank responses were excluded from analysis.Results: The leading challenges reported by surgeons were decreased ability to perform physical examinations (38.6%), possible increased medicolegal exposure (19.3%), and lack of reimbursement parity compared to traditional visits (15.5%). Fewer than 9.0% of respondents experienced technological issues. On average, respondents agreed that telemedicine increases access to care for rural/long-distance patients, provides societal cost savings, and increases patient convenience. Responses were mixed about whether telemedicine leads to greater patient satisfaction. North Americans experienced the most challenges, but also thought telemedicine carried the most benefits, whereas Africans reported the fewest challenges and benefits. Age did not affect responses.Conclusion: Spine surgeons are supportive of the benefits of telemedicine, and only a small minority experienced technical issues. The decreased ability to perform the physical examination was the top challenge and remains a major obstacle to virtual care for spine surgeons around the world, although interestingly, 61.4% of providers did not acknowledge this to be a major challenge. Significant groundwork in optimizing remote physical examination maneuvers and achieving legal and reimbursement clarity is necessary for widespread implementation. [ABSTRACT FROM AUTHOR]

Purpose: To utilize data from a global spine surgeon survey to elucidate (1) overall confidence in the telemedicine evaluation and (2) determinants of provider confidence. Methods: Members of AO Spine International were sent a survey encompassing participant's experience with, perception of, and comparison of telemedicine to in-person visits. The survey was designed through a Delphi approach, with four rounds of question review by the multi-disciplinary authors. Data were stratified by provider age, experience, telemedicine platform, trust in telemedicine, and specialty. Results: Four hundred and eighty-five surgeons participated in the survey. The global effort included respondents from Africa (19.9%), Asia Pacific (19.7%), Europe (24.3%), North America (9.4%), and South America (26.6%). Providers felt that physical exam-based tasks (e.g., provocative testing, assessing neurologic deficits/myelopathy, etc.) were inferior to in-person exams, while communication-based aspects (e.g., history taking, imaging review, etc.) were equivalent. Participants who performed greater than 50 visits were more likely to believe telemedicine was at least equivalent to in-person visits in the ability to make an accurate diagnosis (OR 2.37, 95% C.I. 1.03–5.43). Compared to in-person encounters, video (versus phone only) visits were associated with increased confidence in the ability of telemedicine to formulate and communicate a treatment plan (OR 3.88, 95% C.I. 1.71–8.84). Conclusion: Spine surgeons are confident in the ability of telemedicine to communicate with patients, but are concerned about its capacity to accurately make physical exam-based diagnoses. Future research should concentrate on standardizing the remote examination and the development of appropriate use criteria in order to increase provider confidence in telemedicine technology. [ABSTRACT FROM AUTHOR]

Glaciers in High Mountain Asia generate meltwater that supports the water needs of 250 million people, but current knowledge of annual accumulation and ablation is limited to sparse field measurements biased in location and glacier size. Here, we present altitudinally-resolved specific mass balances (surface, internal, and basal combined) for 5527 glaciers in High Mountain Asia for 2000–2016, derived by correcting observed glacier thinning patterns for mass redistribution due to ice flow. We find that 41% of glaciers accumulated mass over less than 20% of their area, and only 60% ± 10% of regional annual ablation was compensated by accumulation. Even without 21st century warming, 21% ± 1% of ice volume will be lost by 2100 due to current climatic-geometric imbalance, representing a reduction in glacier ablation into rivers of 28% ± 1%. The ablation of glaciers in the Himalayas and Tien Shan was mostly unsustainable and ice volume in these regions will reduce by at least 30% by 2100. The most important and vulnerable glacier-fed river basins (Amu Darya, Indus, Syr Darya, Tarim Interior) were supplied with >50% sustainable glacier ablation but will see long-term reductions in ice mass and glacier meltwater supply regardless of the Karakoram Anomaly. Glaciers in High Mountain Asia are a key water resource. The authors use remote sensing data and a regional implementation of the continuity equation to quantify glacier ablation and accumulation rates for 2000–2016, and establish current climatic-geometric imbalances that imply strong reductions in ice volume by 2100. [ABSTRACT FROM AUTHOR]

Purpose: Spine surgeons around the world have been universally impacted by COVID-19. The current study addressed whether prior experience with disease epidemics among the spine surgeon community had an impact on preparedness and response toward COVID-19. Methods: A 73-item survey was distributed to spine surgeons worldwide via AO Spine. Questions focused on: demographics, COVID-19 preparedness, response, and impact. Respondents with and without prior epidemic experience (e.g., SARS, H1NI, MERS) were assessed on preparedness and response via univariate and multivariate modeling. Results of the survey were compared against the Global Health Security Index. Results: Totally, 902 surgeons from 7 global regions completed the survey. 24.2% of respondents had prior experience with global health crises. Only 49.6% reported adequate access to personal protective equipment. There were no differences in preparedness reported by respondents with prior epidemic exposure. Government and hospital responses were fairly consistent around the world. Prior epidemic experience did not impact the presence of preparedness guidelines. There were subtle differences in sources of stress, coping strategies, performance of elective surgeries, and impact on income driven by prior epidemic exposure. 94.7% expressed a need for formal, international guidelines to help mitigate the impact of the current and future pandemics. Conclusions: This is the first study to note that prior experience with infectious disease crises did not appear to help spine surgeons prepare for the current COVID-19 pandemic. Based on survey results, the GHSI was not an effective measure of COVID-19 preparedness. Formal international guidelines for crisis preparedness are needed to mitigate future pandemics. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a mood disorder with genetic and neurobiological underpinnings, characterized primarily by recurrent episodes of mania and depression, with notable disruptions in rhythmic behaviors such as sleep, energy, appetite and attention. The chronobiological links to BD are further supported by the effectiveness of various treatment modalities such as bright light, circadian phase advance, and mood-stabilizing drugs such as lithium that have effects on the circadian clock. Over the past 30 years, the neurobiology of the circadian clock has been exquisitely described and there now exists a detailed knowledge of key signaling pathways, neurotransmitters and signaling mechanisms that regulate various dimensions of circadian clock function. With this new wealth of information, it is becoming increasingly plausible that new drugs for BD could be made by targeting molecular elements of the circadian clock. However, circadian rhythms are multidimensional and complex, involving unique, time-dependent factors that are not typically considered in drug development. We review the organization of the circadian clock in the central nervous system and briefly summarize data implicating the circadian clock in BD. We then consider some of the unique aspects of the circadian clock as a drug target in BD, discuss key methodological considerations and evaluate some of the candidate clock pathways and systems that could serve as potential targets for novel mood stabilizers. We expect this work will serve as a roadmap to facilitate the development of compounds acting on the circadian clock for the treatment of BD. [ABSTRACT FROM AUTHOR]

Understanding the interplay between climate, fuel and fire is necessary for developing strategies that minimize the negative impacts of fire on people and ecosystems. Here, we aim to investigate whether past fires limit fire activity by reducing fuel availability ('fire leverage') in Catalonia (NE Spain; 32,107 km2), a Mediterranean region encompassing diverse landscapes of agricultural plains and pine–oak mosaics. We built a hierarchical model to assess variations in annual burnt area in relation to weather, past fires and time for a 40-year period (1976–2015). The model also quantified how mean annual wind speed and the arrangement of forests modulated leverage. We found that the cumulated burnt area in the last 6–7 years reduced the re-occurrence of fires. Annual burnt area increased with both dry weather conditions and the number of hot days (≥ 30°C) and showed a moderate decline over the 40-year time series. Model outputs provided some evidence that landscapes with higher mean annual wind speed had lower fire leverage and landscapes with more continuous forest cover had higher fire leverage; however, the statistical uncertainty surrounding the effects of these two relationships was high. In summary, our results show that climate–fire relationships in Mediterranean landscapes are dynamic: fires create short-lived conditions where fuels limit future fire activity in fire regimes usually limited by weather. Our work highlights the multiple factors regulating leverage and helps to understand the interplay between climate, vegetation and recurrent fires in shaping fire regimes. [ABSTRACT FROM AUTHOR]

Background: Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite aggressive multimodal therapy. ATC has a high prevalence of BRAFV600E mutations and is associated with an immunosuppressive microenvironment; we previously demonstrated that the combination of BRAF inhibitor and checkpoint inhibitor immunotherapy synergistically reduce tumour volume in an immunocompetent mouse model of orthotopic ATC.Methods: We again utilised our mouse model of ATC to assess the combination of BRAFV600E inhibitor PLX4720 and anti-PD-L1 or anti-PD-1 antibody on survival, and performed immune cell profiling of lymphoid and myeloid-lineage cells during maximal treatment response and tumour regrowth.Results: Combination therapy dramatically improved mouse survival. Maximal tumour reduction was associated with increases in the number and cytotoxicity of CD8+ T cells and NK cells, as well as increases in mostly M1-polarised tumour-associated macrophages (TAM) and decreases in myeloid-derived suppressor-like cells. Regrowth of tumour occurred after 2-3 weeks of ongoing combination therapy, and was most significantly associated with decreased TAMs and a dramatic increase in M2-polarisation.Conclusions: Combination of PLX4720 and anti-PD-L1/PD-1 antibody dramatically reduced tumour volume, prolonged survival and improved the anti-tumour immune profile in murine ATC. Tumour growth inevitably recurred and demonstrated re-emergence of an immunosuppressive tumour microenvironment. [ABSTRACT FROM AUTHOR]

Purpose: Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I&T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes. In this study, we examine whether PSMA-I&T has comparative efficacy, such that it could replace PSMA-HBED as a diagnostic agent in prostate carcinoma. Methods: 19 patients with PCa referred for Ga-PSMA imaging were imaged with PSMA-HBED and PSMA-I&T PET-CT imaging within a 2-week period. The two pharmaceuticals were synthesised using click chemistry. Imaging was performed using the same standardised methodology on a Siemens Biograph mCT. All sites of PSMA binding thought to represent PCa (probable or definite) were included in a lesion analysis that examined lesion concordance and lesional binding efficiency (SUV) between the two radiopharmaceuticals. For each patient, SUV of the LV cavity blood pool, bone, muscle and liver were determined as image background measures. Results: Across all patients, PSMA uptake was observed in 47 lesions (10 bone lesions, 19 nodal lesions, 18 high-grade intraprostatic binding). Lesions were concordant between the agents in all except for two small (<4 mm) nodal lesions which were not visualised with PSMA-I&T. SUV assessment showed significantly greater overall lesion binding with HBED (paired t test, p = 0.0001). LV blood pool and bone marrow SUV were significantly higher for I&T than HBED (paired t test, blood pool p < 1 × 10-5, bone marrow p < 0.005). Conclusion: Intra-patient comparative imaging demonstrates higher lesional PSMA-HBED binding than PSMA-I&T and that the HBED agent is likely to have better lesion contrast. While there was concordance in 96% of lesions, 2 small nodal lesions were appreciated with PSMA-HBED imaging while considered normal with PSMA-I&T. These findings suggest that HBED-PSMA has a slightly higher diagnostic accuracy in comparison to PSMA-I&T. [ABSTRACT FROM AUTHOR]

The eradication of newly detected alien plant species is often prescribed, but rarely successful. Eradication programs fail for many reasons, however, for eradication to remain a cost-efficient management option it is clear that good decisions must be made at the outset. Here we re-frame the project prioritization protocol (PPP), a tool widely used in conservation biology, for use with the metrics typically used by a biosecurity agency. We then use existing methods to estimate the cost-efficiency of eradicating 50 hypothetical species incursions and compare the reduction in weed risk achieved by allocating resources using the PPP framework with the allocation based on risk ranking. By allocating resources to plant eradication programs using the PPP our analysis indicated that it is possible to improve the return on public expenditure by 25% compared to investing based solely on weed risk assessment scores. We also demonstrate how the cost-efficiency of the overall portfolio is influenced by the choice of planning horizon; including the decline in overall portfolio performance that arises when attempting to eradicate individual species too quickly. Finally, we discuss the logistical benefits to a management agency that arise from the use of a generic overarching framework such as the PPP. We believe that the PPP has considerable potential for use in biosecurity and can help focus attention on those species where management can make the biggest difference. [ABSTRACT FROM AUTHOR]

Caregivers of youth with behavioral health conditions often experience significant and chronic caregiving strain. Caregiving strain is thought to consist of three dimensions: objective strain (observable negative events), subjective internalized strain (negative feelings directed inwardly), and subjective externalized strain (negative feelings directed outwardly). Based on a modified stress process model, the aims of this study were to: (1) examine whether the association between youth emotional-behavioral problem severity (measured with the Child Behavior Checklist/6-18) and subjective internalized and subjective externalized caregiving strain is mediated by objective strain for caregivers, and; (2) identify other predictors of subjective internalized and subjective externalized strain, particularly related to youth emotional-behavioral strengths as measured by the Behavioral and Emotional Rating Scale-Parent Rating Scale. We also explored the extent to which the association between youth emotional-behavioral problem severity and subjective internalized and subjective externalized strain may be moderated by perceived youth emotional-behavioral strengths. One-hundred and eighty-five ( N = 185) caregivers of youth served by a community-based system of care participated in structured survey interviews at program enrollment. Regression analyses indicated that objective strain was found to fully mediate the association between youth emotional-behavioral problem severity and subjective externalized strain. Greater youth strengths related to family involvement were also associated with lower subjective externalized strain. Higher caregiver age, lower education, biological parent relationship to youth, greater youth emotional-behavioral problem severity, higher objective strain, and lower youth strengths related to school functioning were associated with higher subjective internalized strain. A significant interaction was found between youth problem severity, youth affective strengths, and subjective internalized strain such that caregivers who reported higher levels of youth affective strengths experienced stronger effects from youth emotional-behavioral problem severity on subjective internalized strain. These findings shed light upon the complex set of circumstances that may lead caregivers of youth with behavioral health conditions to experience subjective internalized and subjective externalized strain. [ABSTRACT FROM AUTHOR]

As the field of clinical ethics consultation sets standards and moves forward with the Quality Attestation process, questions should be raised about what ethical issues really do arise in practice. There is limited data on the type and number of ethics consultations conducted across different settings. At Loyola University Medical Center, we conducted a retrospective review of our ethics consultations from 2008 through 2013. One hundred fifty-six cases met the eligibility criteria. We analyzed demographic data on these patients and conducted a content analysis of the ethics consultation write-ups coding both the frequency of ethical issues and most significant, or key, ethical issue per case. Patients for whom ethics consultation was requested were typically male (55.8 %), white (57.1 %), between 50 and 69 years old (38.5 %), of non-Hispanic origin (85.9 %), and of Roman Catholic faith (43.6 %). Nearly half (47.4 %) were in the intensive care unit and 44.2 % died in the hospital. The most frequent broad ethical categories were decision-making (93.6 %), goals of care/treatment (80.8 %), and end-of-life (73.1 %). More specifically, capacity (57.1 %), patient's wishes/autonomy (54.5 %), and surrogate decision maker (51.3 %) were the most frequent particular ethical issues. The most common key ethical issues were withdrawing/withholding treatment (12.8 %), patient wishes/autonomy (12.2 %), and capacity (11.5 %). Our findings provide additional data to inform the training of clinical ethics consultants regarding the ethical issues that arise in practice. A wider research agenda should be formed to collect and compare data across institutions to improve education and training in our field. [ABSTRACT FROM AUTHOR]

The American Society for Bioethics and Humanities has created a quality attestation (QA) process for clinical ethics consultants; the pilot phase of reviewing portfolios has begun. One aspect of the QA process which is particularly challenging is assessing the interpersonal skills of individual clinical ethics consultants. We propose that using case simulation to evaluate clinical ethics consultants is an approach that can meet this need provided clear standards for assessment are identified. To this end, we developed the Assessing Clinical Ethics Skills (ACES) tool, which identifies and specifies specific behaviors that a clinical ethics consultant should demonstrate in an ethics case simulation. The aim is for the clinical ethics consultant or student to use a videotaped case simulation, along with the ACES tool scored by a trained rater, to demonstrate their competence as part of their QA portfolio. The development and piloting of the tool is described. [ABSTRACT FROM AUTHOR]

The early detection of newly naturalised alien species is vital to ensuring the greatest chance of their successful eradication. Understanding where species naturalise most frequently is the first stage in allocating surveillance effort. Using Australia's Virtual Herbarium, we compiled the collection records for all plant species in Australia. We controlled for potential spatial biases in collection effort to identify areas that have an elevated rate of first records of alien species' occurrence in Australia. Collection effort was highly variable across Australia, but the most intense collection effort occurred either close to herbaria (located in cities) or in remote natural environments. Significant clusters of first records of occurrence were identified around each state's capital city, coinciding with higher collection effort. Using Poisson point process modelling, we were able to determine the relative influence of environmental and anthropogenic factors on the spatial variation in the risk of species naturalisation. Effort-corrected naturalisation risk appeared to be strongly related to land use, road and human population densities, as well as environmental factors such as average temperature and rainfall. Our paper illustrates how the risk of naturalisation at a location can be estimated quantitatively. Improved understanding of factors that contribute to naturalisation risk enhances allocation of surveillance effort, thereby detecting novel species sooner, and increasing the likelihood of their eventual eradication. [ABSTRACT FROM AUTHOR]

The article presents a study investigating the prevalence of depressive symptoms after stroke among different age groups. The findings revealed that both young and old stroke victims experienced high levels of depressive symptoms, that high financial, family, and health-related stress were present on patients at risk for clinical depression at 3 months, and that there is no proof that younger survivors who reported higher subjective stress would experience a higher level of depressive symptoms.

Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca2+ imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment. [ABSTRACT FROM AUTHOR]

We document the successful establishment of a European newt ( Lissotriton vulgaris) in south-eastern Australia, the first recorded case of a caudate species establishing beyond its native geographic range in the southern hemisphere. Field surveys in south-eastern Australia detected L. vulgaris at six sites, including four sites where the species had been detected 15 months earlier. Larvae were detected at three sites. Individuals had identical NADH dehydrogenase subunit 2 and cytb mtDNA gene sequences, and comparisons with genetic data from the species' native range suggest that these individuals belong to the nominal subspecies L. v. vulgaris. Climatic conditions across much of southern Australia are similar to those experienced within the species' native range, suggesting scope for substantial range expansion. Lissotriton vulgaris had been available in the Australian pet trade for decades before it was declared a 'controlled pest animal' in 1997, and thus the invasion documented here likely originated via the release or escape of captive animals. Lissotriton vulgaris is the sole member of an entire taxonomic order to have established in Australia, and given the potential toxicity of this species, further work is needed to delimit its current range and identify potential biodiversity impacts. [ABSTRACT FROM AUTHOR]

Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian 'clock genes' commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. [ABSTRACT FROM AUTHOR]

This paper examines three of Australia’s earliest port-related structure studies. Excavations conducted in 1984 and 1994 in vastly different circumstances, with markedly different oceanographic conditions, progressing through quite different substrates, were joined with 1993–1994 overview of all the port structures along the coast of Western Australia. Providing a better appreciation of submerged port-related structure studies as a bona fide part of maritime archaeology, these three studies and have ramifications for future work both in Australia and overseas. [ABSTRACT FROM AUTHOR]

The temporal and spatial evolution of concentration profiles of bovine serum albumin (BSA) in various cellulosic fiber beds is measured using magnetic resonance imaging. Effective diffusivities are calculated using a numerical one dimensional Fickian model to match experimental concentration profiles. Experimental values of the diffusivities are compared with predictions from a simple diffusion-adsorption model which accounts for porosity, tortuosity, and surface adsorption. BSA was found to have negligible adsorption in the concentration range studied, resulting in a simplified diffusion model based on fiber characteristics and geometry. Effective diffusivities agreed well with the predicted values and were within an order of magnitude of the estimated bulk diffusivity of BSA. [ABSTRACT FROM AUTHOR]

Translocation of threatened species is a tool used increasingly to conserve biodiversity, but the suite of co-dependent species that use the threatened taxa as hosts can be overlooked. We investigate the preliminary impact of translocating three threatened plant species on insect species and the integrity of insect assemblages that depend on these plants as their hosts. We compare the insect assemblages between natural populations of the threatened species, related non-threatened plant species growing wild near the threatened plants, and threatened plants translocated to another site approximately 40 km away. We used host breadth models and a coextinction risk protocol to determine which insect species are potentially host-specific on the threatened plants, and then assessed these insects' potential presence at the translocation site. We found that insect assemblages on naturally-occurring threatened plants had more individuals, higher species density and higher species richness than assemblages on translocated plants. For one plant species, Leucopogon gnaphalioides, species composition differed significantly between wild and translocated populations ( P < 0.001). Furthermore, four insect species that were host-specific to Banksia brownii and B. montana were not detected on the translocated plants. Instead, translocated plants supported insect assemblages more similar to those of related plant species from the surrounding area. We conclude that threatened plant translocations that involve seed collection and propagation may have limited benefit for individual dependent species or the supported insect assemblage. Additional conservation actions will be required to maintain the diversity of insect assemblages and host-dependent relationships. [ABSTRACT FROM AUTHOR]

Rationale: The transcription factor cAMP response element binding (CREB) protein plays a pivotal role in drug-dependent neuronal plasticity. CREB phosphorylation at Ser133 is enhanced by drugs of abuse, including nicotine. Dynorphin (Dyn) contributes to the addictive process and its precursor gene prodynorphin (PD) is regulated by CREB. PD mRNA and Dyn synthesis were enhanced in the striatum following acute nicotine, suggesting genomic regulation. Objective: These studies investigated PD transcription in mice acutely treated with nicotine, determined the role of CREB, and characterized the receptors involved. Results: Acute nicotine increased adenylyl cyclase activity, cAMP, and pCREB Ser133 levels in striatum and enhanced CREB binding to CRE elements (DynCREs) of the PD promoter, preferentially DynCRE3. DynCRE3 binding was dose dependent with 1 mg of nicotine giving a maximal response. Additionally, DynCRE binding was time dependent, rising by 15 min, reaching a maximum at 1 h, and returning to control by 3 h, a temporal pattern similar to that of cAMP and pCREB. Supershift experiments showed that CREB and pCREB Ser133 were the major contributors to DynCRE3 binding complex. The nAChR antagonist mecamylamine and the dopamine D1-like receptor antagonist SCH 23390 prevented the nicotine-induced increase of pCREB and nuclear protein binding to DynCRE3. Conclusions: Our findings suggest that nicotine regulates PD expression in striatum at the transcriptional level and CREB is involved. Dopamine D1 receptor stimulation by nAChR-released dopamine appears to be an underlying mechanism. Altered Dyn synthesis might be relevant for the behavioral actions of nicotine and especially its aversive properties. [ABSTRACT FROM AUTHOR]

Occupancy-based monitoring programs rely on survey data to infer presence or absence of the target species. However, species may occupy a site and go undetected, leading to erroneous inference of absence ('false absence'). If detectability is influenced by the time of year or weather conditions, survey protocols can be adjusted to minimize the chance of false absences. In this study, detection probabilities for three amphibian species from south-eastern Australia were modelled using a Bayesian approach. For aural surveys, we compared basic models, which only included effects of survey date, duration and time of day on detection, to models including additional effects of weather. Model selection using deviance information criterion (DIC) suggested that the basic model was the most parsimonious for Crinia signifera, while models including relative humidity and water temperature were most supported for Limnodynastes dumerilii and L. tasmaniensis respectively. When predictive performance was assessed by cross validation, DIC results were largely matched for C. signifera and L. dumerilii, while models of detection for L. tasmaniensis were indistinguishable, AUC scores suggesting inadequate performance. We show how results such as these can be used to design surveys, developing protocols for individual surveys and estimating the number of surveys required under those protocols to achieve a threshold cumulative probability of detection. Conservation managers can use these models to maximize the efficiency of surveys. This will improve the accuracy of occupancy data, and reduce the risk of misdirected conservation actions resulting from false absences. [ABSTRACT FROM AUTHOR]

Cellulosic biomass is recalcitrant to enzymatic hydrolysis which greatly reduces the efficiency of biofuels production. Specifically, the lignin component of biomass is thought to provide non-productive binding sites for glycosyl hydrolases, effectively disabling the enzymes from completing further digestion. A thorough understanding of the adsorption rates of protein molecules on celluloses-especially lignocelluloses-is crucial to improving the cyclic steps of adsorption, diffusion, and reaction. We use magnetic resonance imaging (MRI) to detect concentrations of bovine serum albumin (BSA) in equilibrium with various cellulose substrates, including delignified and acid-treated lignocellulosic substrates. BSA is believed to be an effective adsorption blocker during enzymatic hydrolysis of lignocellulosics, and has been correlated with an increase in reaction yield. We found BSA to have little adsorption onto the chosen cellulose substrates in the low concentration range studied. Ultraviolet (UV) absorption measurements of reaction supernatants at 280 nm were used to confirm the MRI results for each of the substrate types. The advantages of the MRI technique are compared with that of the traditional UV measurement. [ABSTRACT FROM AUTHOR]

Water is essential to the hydrolysis and conversion of lignocellulosic materials as it is both the medium through which enzymes diffuse to and products diffuse away from the reaction sites and a reactant in the hydrolysis reaction of the glycosidic bonds within the polysaccharides. However, little is known about how water interactions with the biomass change with solids content and how this affects mass transfer resistances during high solids saccharification. Nuclear magnetic resonance spectroscopy measurements of the T relaxation times of water in cellulose suspensions were used to demonstrate that increases in solids content led to increases in the physical constraint of water in the suspensions. Moreover, the addition of either glucose (a monosaccharide which end-product inhibits β-glucosidase) or mannose (a stereoisomer of glucose that does not end-product inhibit β-glucosidase) further increased water constraint at all solids contents. The presence of either monosaccharide constrained water and inhibited saccharification rates to similar extents. This observation, coupled with the absence of cellobiose produced in the reactions, demonstrated that the presence of soluble sugars can negatively impact saccharification efficiency simply by increasing water constraint in cellulose suspensions before impacting enzyme activity. Furthermore, results are presented that demonstrate strong correlations between water constraint in cellulose suspensions with diffusivities of enzyme and monosaccharides within the system. These results are discussed in the context of increased viscosity of the aqueous fraction in the suspension resulting from increased water-cellulose and water-solute interactions that ultimately increases diffusion resistances and decreases saccharification rates. [ABSTRACT FROM AUTHOR]

Rationale: The synthesis and release of met-enkephalin and β-endorphin, endogenous ligands for δ-opioid peptide receptors (DOPrs), are altered following nicotine administration and may play a role in nicotine addiction. Objectives: To investigate the consequences of altered opioidergic activity on DOPr expression, coupling, and function in striatum during early nicotine withdrawal. Methods: Mice received nicotine-free base, 2 mg/kg, or saline, subcutaneously (s.c.), four times daily for 14 days and experiments performed at 24, 48, and 72 h after drug discontinuation. DOPr binding and mRNA were evaluated by [ H]naltrindole autoradiography and in situ hybridization. DOPr coupling and function were investigated by agonist pCl-DPDPE-stimulated [ S]GTPγS binding autoradiography and inhibition of adenylyl cyclase activity. Results: During nicotine withdrawal DOPr binding was unaltered in caudate/putamen (CPu) and nucleus accumbens (NAc) shell and core. Receptor mRNA was slightly increased in the shell at 72 h, but significant elevations were observed in prefrontal cortex and hippocampus. pCl-DPDPE-stimulated [ S]GTPγS binding was attenuated in NAc, but not CPu. In the shell, binding was decreased by 48 h and remained decreased over 72 h; while in the core, significant reduction was seen at 72 h. Basal adenylyl cyclase activity was suppressed in striatum at 24 h, but recovered by 48 h. DOPr stimulation with pCl-DPDPE failed to inhibit adenylyl cyclase activity at 24 h and produced attenuated responses at 48 and 72 h. Conclusions: These observations suggest that DOPr coupling and function are impaired in the NAc during nicotine withdrawal. DOPr desensitization might be involved in the affective component of nicotine withdrawal. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to assess the utility of F-fluorocholine (FCH), compared to standard imaging of bone scan (BS) and contrast-enhanced abdominopelvic computed tomography (CT), in patients with castration-resistant prostate carcinoma. Methods: FCH has shown promise as a metabolic imaging agent for prostate carcinoma. Twenty-six patients with castration-resistant prostate carcinoma had FCH, BS and CT imaging within a 2-month period. Individual FCH-positive lesions in bone were compared to the BS and soft tissue lesions were compared to CT. The lesions were then classified as concordant or discordant for the presence or absence of prostate cancer metastases. Discordant bone or soft tissue lesions were followed up with BS or CT, respectively, at 6-month intervals for up to 2 years or until a definitive diagnosis of the discordant lesion could be made. Results: In 13 (50%) of the patients, all lesions identified were concordant; this included 5 patients in whom no lesions could be identified with any imaging modality. In 21 patients, 183 lesions were observed with 149 being concordant and 34 (19%) being discordant (13 patients). Based on follow-up, FCH correctly identified the presence or absence of disease in 27 of 34 lesions, and in 14 cases FCH-positive lesions, not identified on initial imaging, were confirmed as disease on follow-up. The sensitivity, specificity, accuracy, positive predictive and negative predictive values for lesion detection by FCH are 96% (92-98%), 96% (81-99%), 96% (93-97%), 99% (96-100%) and 81% (64-88%), respectively, with 95% confidence intervals shown in parentheses. Conclusion: In this patient cohort, FCH shows good initial concordance (81%) with BS and CT in the detection of metastatic prostate carcinoma. Follow-up of the cases where FCH was initially discordant with subsequent BS or CT shows that FCH was accurate in determining the presence or absence of prostate metastasis in 79% of lesions. While FCH imaging as compared to BS and CT in this patient group has a good sensitivity and specificity for the detection of lesions representing prostate metastasis, further prospective studies are needed to determine its role. [ABSTRACT FROM AUTHOR]