Search

Context Mapping of vegetation is important in understanding its dynamics in relation to climate change and disturbance. We investigated using species distribution models to predict plant species assemblages in a subantarctic environment where traditional image interpretation methods of vegetation mapping are limited by image availability and ability to discriminate vegetation types. Aims We test the efficacy for mapping of modelling the range and core range of common species. We also determine the relative importance of predictor variables for each of nine species. Methods We used random forest models to predict the total range and core range (>25% projected foliage cover) of nine potentially dominant plant species and determined the contributions of predictor variables to the models for each species. Key results Widespread species with extensively overlapping ranges were spatially more partitioned with modelling based on core range than with presence or absence modelling. The core range input produced a vegetation map that better approximated observed vegetation patterns than that from presence or absence data. The most important predictor variable varied between species, with elevation, distance from coast, latitude and an across island gradient (similar to longitude) being most influential. Conclusions Species distribution models using three categories (absent

Introduction: The evolving treatment landscape for non-small-cell lung cancer (NSCLC) and complexities of regulations and reimbursement present challenges to community oncologists. Clinical pathways are tools to optimize care, but information on their value in the real world is limited. This retrospective study assessed treatment patterns and clinical outcomes in patients with stage I–III NSCLC pre- and post-pathways implementation at Tennessee Oncology, a large, community-based oncology practice in the USA. Methods & Materials: Chart data were abstracted for adults diagnosed with stage I–III NSCLC who received systemic treatment. Patients were divided into pre-pathways (treatment initiation 2014–2015) and post-pathways (treatment initiation 2016–2018) cohorts. Patient characteristics, treatment patterns and outcomes were summarized descriptively. Kaplan–Meier curves were used to assess time-dependent outcomes, and log-rank test was used to compare the cohorts. Results: 291 patients were included (stage I–II: 38 pre-pathways, 55 post-pathways; stage III: 105 pre-pathways, 93 post-pathways). Duration on first-line (1L) therapy was similar for stage I–II patients pre- and post-pathways (median 1.9 months vs 2.1 months; p = 0.75), but increased for stage III patients post-pathways (2.1 months vs 1.4 months pre-pathways; p Conclusion: Given that improvements in rates of treatment response post-pathways occurred only for patients diagnosed with stage III NSCLC, among whom immunotherapy uptake increased post-pathways, such improvements may be attributable to evolving practices in cancer care, including advances in treatment and care delivery, rather than clinical pathways implementation. Further research is warranted to assess the impact of clinical pathways in the current treatment era, given that immunotherapy has now become the standard of care in NSCLC.

Phosphatase and tensin homolog (PTEN) is a major negative regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway. Loss-of-function mutations inPTENhave been found in a subset of patients with macrocephaly and autism spectrum disorder (ASD). PTEN loss in neurons leads to somal hypertrophy, aberrant migration, dendritic overgrowth, increased spine density, and hyperactivity of neuronal circuits. These neuronal overgrowth phenotypes are present onPtenknock-out (KO) and reconstitution with autism-associated point mutations. The mechanism underlying dendritic overgrowth inPtendeficient neurons is unclear. In this study, we examined howPtenloss impacts microtubule (MT) dynamics in both sexes using retroviral infection and transfection strategies to manipulate PTEN expression and tag the plus-end MT binding protein, end-binding protein 3 (EB3). We foundPtenKO neurons sprout more new processes over time compared with wild-type (WT) neurons. We also found an increase in MT polymerization rate inPtenKO dendritic growth cones. Reducing MT polymerization rate to the WT level was sufficient to reduce dendritic overgrowth inPtenKO neuronsin vitroandin vivo. Finally, we found that rescue of dendritic overgrowth via inhibition of MT polymerization was sufficient to improve the performance ofPtenKO mice in a spatial memory task. Taken together, our data suggests that one factor underlying PTEN loss dependent dendritic overgrowth is increased MT polymerization. This opens the possibility for an intersectional approach targeting MT polymerization and mTOR with low doses of inhibitors to achieve therapeutic gains with minimal side effects in pathologies associated with loss of neuronal PTEN function.SIGNIFICANCE STATEMENTLoss ofPtenfunction because of genetic deletion or expression of mutations associated with autism spectrum disorder (ASD), results in overgrowth of neurons including increased total dendritic length and branching. We have discovered that this overgrowth is accompanied by increased rate of microtubule (MT) polymerization. The increased polymerization rate is insensitive to acute inhibition of mechanistic target of rapamycin (mTOR)C1 or protein synthesis. Direct pharmacological inhibition of MT polymerization can slow the polymerization rate inPtenknock-out (KO) neurons to rates seen in wild-type (WT) neurons. Correction of the MT polymerization rate rescues increased total dendritic arborization and spatial memory. Our studies suggest that phosphatase and tensin homolog (PTEN) inhibits dendritic growth through parallel regulation of protein synthesis and cytoskeletal polymerization.

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .

Nucleoporin 98 is a nuclear pore complex component that is mislocalized in Alzheimer’s disease and the alteration in nucleoporin 98 has been attributed to tau. In order to determine if nucleoporin 98 mislocalization is a general feature of tauopathies, we assessed the localization of nucleoporin 98 in neurons in primary tauopathies, including frontotemporal lobar degeneration-tau, corticobasal degeneration and progressive supranuclear palsy. Immunofluorescence staining was performed on frontal cortex and occipital cortex tissue from cases of primary tauopathies and controls without neurodegenerative disease using antibodies to identify nucleoporin 98, phospho-tau (Ser202, Thr205) monoclonal antibody and neuronal marker microtubule-associated protein 2. The stained tissue was imaged by fluorescence microscopy and the number of neurons with mislocalized nucleoporin 98 and phospho-tau (Ser202, Thr205) monoclonal antibody staining was quantified. In frontal cortex tissue, all primary tauopathies examined demonstrated significantly increased numbers of neurons with abnormal localization of nucleoporin 98 along the nuclear envelope compared with control tissue. Additionally, frontotemporal lobar degeneration-tau and corticobasal degeneration in the frontal cortex demonstrated significantly increased numbers of neurons with a cytoplasmic mislocalization of nucleoporin 98 compared with control tissue. The number of neurons with mislocalized nucleoporin 98 was significantly correlated with the number of neurons with phospho-tau (Ser202, Thr205) monoclonal antibody-positive tau staining. In the occipital cortex, which is relatively spared from pathological tau accumulations in these primary tauopathies, the localization of nucleoporin 98 was not significantly altered. This study demonstrates that nucleoporin 98 mislocalization is a feature of primary tauopathies and is associated with pathological tau accumulation. In the context of prior research demonstrating nucleoporin 98 mislocalization in Alzheimer’s disease and an interaction between tau and nucleoporin 98, these results further support the hypothesis that pathological tau may contribute to nucleoporin 98 mislocalization. Given the critical role of the nuclear pore complex in nucleocytoplasmic transport, the identification of nucleoporin 98 mislocalization in primary tauopathies highlights a potential pathophysiological disruption in these disorders.

The text of Donne’s verse letter to Sir Henry Wotton on his appointment as ambassador to Venice, beginning ‘After those reverent papers’, published in the Variorum edition of the verse letters (2018) is based on Trinity College, Dublin Ms. 877 (Variorum siglum DT1). While the Variorum text resembles most of the printed versions of the poem, I argue that it differs considerably from what Donne likely presented to Wotton as he left England for his embassy in 1604. I base my argument principally upon bibliographic evidence found in the Burley Ms. (Variorum siglum LR1), which was compiled mainly during Wotton’s first embassy (1604–1610). Below the copy of HWVenice (Variorum short form) in this manuscript, the scribe recorded a prose postscript that in all likelihood was taken from the now lost original holograph among Wotton’s personal papers in Venice. No other copy of HWVenice includes this postscript, a fact leaving little doubt that the LR1 text of the poem and its postscript stand closer to Donne’s own hand than any other surviving witness. After analysing the stemma published in the Variorum, I propose a more likely stemma and a more authoritative text for HWVenice.

The Triarchic Psychopathy Measure (TriPM) is a self-report scale based on the Triarchic Model that has been little used in research in the criminal justice system. We sought to examine associations between pre-release TriPM components, probation officer relationships, and parolee quality of life, both measured after 2 months in the community, and reconviction 12 months after release. Using data from 234 New Zealand male high-risk prisoners, we tested four multivariate models each across three timepoints. Pre-release, we found Boldness was not predictive, but Meanness predicted poorer relationship quality after 2 months, both from probation officer and parolee perspectives, with the former in turn predicting reconviction within 12 months. Disinhibition predicted 12-month recidivism regardless of relationship quality or external life circumstances. This relationship to recidivism was partially explained in the final model which linked Disinhibition and poorer subjective wellbeing, with the latter in turn predicting recidivism.

Summary A conventional stereo light microscope was used to image polished wood surfaces at cellular resolution over size scales of the growth ring or larger. Bandpass filtering and local area contrast enhancement were used to aid automatic image thresholding and binarisation. An estimate for the location and proportion of cell collapse was introduced based on the distance between uncollapsed cell lumens. Additionally, spatial associations between vessels were determined using a Euclidean distance transform. The analysis of pith to bark cores provided sufficient detail to show significant intra and inter-annual trends in Pinus radiata tracheid dimensions (wall thickness, wall area, and radial widths). These trends were consistent with expectations and in agreement with the literature. Measured cell dimensions may be influenced by cell collapse and deformation as a result of drying. The analysis of air, kiln and oven-dried Eucalyptus nitens showed that cell collapse was highly variable but generally more prominent in the outer third of growth rings. There were significant changes in vessel shape across the growth rings and vessel area was significantly reduced by drying. The technique provides an intermediate step between detailed microscopy and macroscopic imaging that allows spatial analysis at the wood cell level.

PURPOSE To provide standards and practice recommendations specific to telehealth in oncology. METHODS A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies. STANDARDS AND GUIDANCE Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards .

Kienbock's disease is the result of avascular necrosis of the lunate. Whilst no causal aetiology has been identified, several factors have been found to show an association with the condition. These include anatomical aspects such as lunate morphology; wrist biomechanics and vascular supply patterns, which in combination with external influences such as repetitive trauma, maybe a potential cause of the condition. Diagnosis and assessment of severity has historically been made using plain radiographs to stage the condition, however other assessment modalities such as magnetic resonance imaging and direct visualization with wrist arthroscopy have been advocated. Lichtman has sought to amalgamate these diagnostic techniques into a new comprehensive staging tool with the aim of better standardizing and guiding treatment. Whilst no single treatment has been proven to improve the natural outcome of the disease, current recognized treatments, in general, aim to protect the compromised lunate in the early stage of the condition, whilst in the later stages the focus shifts to procedures that either bypass, fuse or excise the affected peri-lunate articulations.

PURPOSE: To provide Standards on the basis of evidence and expert consensus for a pilot of the Oncology Medical Home (OMH) certification program. The OMH model is a system of care delivery that features coordinated, efficient, accessible, and evidence-based care and includes a process for measurement of outcomes to facilitate continuous quality improvement. The OMH pilot is intended to inform further refinement of Standards for OMH model implementation. METHODS: An Expert Panel was formed, and a systematic review of the literature on the topics of OMH, clinical pathways, and survivorship care plans was performed using PubMed and Google Scholar. Using this evidence base and an informal consensus process, the Expert Panel developed a set of OMH Standards. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: Three comparative peer-reviewed studies of OMH met the inclusion criteria. In addition, the results from 16 studies of clinical pathways and one systematic review of survivorship care plans informed the evidence review. Limitations of the evidence base included the small number of studies of OMH and lack of longer-term outcomes data. More data were available to inform the specific Standards for pathways and survivorship care; however, outcomes were mixed for the latter intervention. The Expert Panel concluded that in the future, practices should be encouraged to publish the results of OMH interventions in peer-reviewed journals to improve the evidence base. STANDARDS: Standards are provided for OMH in the areas of patient engagement, availability and access to care, evidence-based medicine, equitable and comprehensive team-based care, quality improvement, goals of care, palliative and end-of-life care discussions, and chemotherapy safety. Additional information, including a Standards implementation manual, is available at www.asco.org/standards .

Silver diamine fluoride (SDF) is a dental biomaterial used to arrest dental caries. To better understand SDF’s mechanism of action, we examined the localization of silver within the tissues of SDF-treated teeth. Carious primary teeth fixed within 2 min of SDF application (SDF-minutes, n = 3), at 3 wk after SDF application in vivo (SDF-weeks, n = 4), and at 2 y after multiple SDF applications in vivo (SDF-multiple, n = 1) were investigated in this study. Carious primary teeth without SDF application (no-SDF, n = 3) served as controls. Mineral density and structural analyses were performed via micro–X-ray computed tomography and scanning electron microscopy. Elemental analyses were performed through X-ray fluorescence microprobe and energy-dispersive X-ray spectroscopic techniques. SDF-treated teeth revealed higher X-ray–attenuated surface and subsurface regions within carious lesions, and similar regions were not present in no-SDF teeth. Regions of higher mineral density correlated with regions of silver abundance in SDF-treated teeth. The SDF penetration depth was approximated to 0.5 ± 0.02 mm and 0.6 ± 0.05 mm (mean ± SD) for SDF-minutes and SDF-weeks specimens, respectively. A higher percentage of dentin tubular occlusion by silver or calcium phosphate particles was observed in primary teeth treated with SDF-weeks as compared with SDF-minutes. Elemental analysis also revealed zinc abundance in carious lesions and around the pulp chamber. SDF-weeks teeth had significantly increased tertiary dentin than SDF-minutes and no-SDF teeth. These results suggest that SDF treatment on primary teeth affected by caries promotes pathologic biomineralization by altering their physicochemical properties, occluding dentin tubules, and increasing tertiary dentin volume. These seemingly serendipitous effects collectively contribute to the cariostatic activity of SDF.

Years before value‐based care agreements and alternative payment methodologies became a reality, community oncology practices had a major blind spot when it came to hospital and emergency departmen...

Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.

The elimination of lymphatic filariasis (LF) is achieved through repeated mass drug administration (MDA) of anti-filarial medications, which interrupts transmission and prevents new infections. Accurate transmission assessments are critical to deciding when to stop MDA. Current methods for evaluating transmission may be insufficiently sensitive, resulting in post-MDA resurgence. We, therefore, evaluated potential diagnostic testing scenarios for post-MDA surveillance. Data were used from two surveys (a household cluster and a cohort) conducted in an area of Mandalay Region, Myanmar, with ongoing transmission following several rounds of MDA. First, age- and sex-adjusted seroprevalence were estimated for the area using the household survey. Next, three Bayesian networks were built from the combined datasets to compare antigens by immunochromatic testing (ICT) and/or Og4C3 enzyme-linked immunosorbent assay (ELISA) and antibody (Ab) detection methods (Wb123 or Bm14 Ab ELISA). The networks were checked for validity and then used to compare diagnostic testing scenarios. The adjusted prevalence from the household survey for antigen, Wb123 Ab and Bm14 Ab were 4.4% (95% CI 2.6–7.3%), 8.7% (5.96–12.5%) and 20.8% (16.0–26.6%), respectively. For the three networks, the True Skill Statistic and Area Under the Receiver Operating Characteristic Curve for antigen, Wb123 and Bm14 Ab were 0.79, 0.68 and 0.55; and 0.97, 0.92 and 0.80, respectively. In the Bayesian network analysis, a positive case was defined as testing positive to one or more infection markers. A missed result was therefore the probability of a positive case having a negative test result to an alternate marker. The probability of a positive case prior to any testing scenario was 17.4%, 16.8% and 26.6% for antigen, Wb123 Ab and Bm14 Ab, respectively. In the antigen-only testing scenario, the probability of a missed positive LF result was 5.2% for Wb123 and 15.6% for Bm14 Ab. The combination of antigen plus Bm14 Ab testing reduced the probability of missing a positive LF case as measured by Wb123 Ab to 0.88%. The combination of antigen plus Wb123 Ab was less successful and yielded an 11.5% probability of a missed positive result by Bm14 Ab testing. Across scenarios, there was a greater discordance between Bm14 and both antigen and Wb123 Ab in the 1–10 age group compared to older ages. These findings suggest that the addition of Bm14 Ab improves the sensitivity of LF testing for current or past infection. The combination of antigen plus Bm14 Ab should therefore be considered for inclusion in post-MDA surveillance to improve the sensitivity of transmission surveys and prevent the premature cessation of MDA.