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In The Right to Higher Education, Christopher Martin develops a powerful, autonomy-based argument that there is a moral right to access to higher education. I raise three concerns about whether this argument succeeds. The first is a concern about the conception of autonomy at the heart of Martin’s argument; the second is a concern about possible overgeneralizations of the argument; and the third is a concern about whether Martin’s view is consonant with judgments about fairness.

ObjectiveNoninvasive ventilation (NIV) improves survival and quality of life in motor neuron disease (MND), but many patients fail to receive effective ventilation. This study aimed to map the respiratory clinical care for MND patients at a service and individual healthcare professional (HCP) level to understand where attention may be needed to ensure all patients receive optimal care.MethodsTwo online surveys of HCPs working with MND patients in the UK were conducted. Survey 1 targeted HCPs providing specialist MND care. Survey 2 targeted HCPs working in respiratory/ventilation services and community teams. Data were analysed using descriptive and inferential statistics.ResultsResponses from 55 HCPs providing specialist MND care who worked at 21 MND care centres and networks and 13 Scotland Health Boards were analysed from Survey 1. Responses from 85 HCPs from respiratory/ventilation services and 73 HCPs from community teams, representing 97 services, were analysed from Survey 2. Significant differences in practice were identified at each stage of the respiratory care pathway as well as evidence of the need for improvement. This included when patients were referred to respiratory services, the time taken waiting to commence NIV, the availability of sufficient NIV equipment and provision of services, particularly out of hours.ConclusionWe have highlighted significant disparity in MND respiratory care practices. Increased awareness of the factors that influence NIV success and the performance of individuals and services is important for optimal practice.

1. Genetic diversity is one of the three main levels of biodiversity recognised in the Convention on Biological Diversity (CBD). Fundamental for species adaptation to environmental change, genetic diversity is nonetheless under-reported within global and national indicators. When it is reported, the focus is often narrow and confined to domesticated or other commercial species. 2. Several approaches have recently been developed to address this shortfall in reporting on genetic diversity of wild species. While multiplicity of approaches is helpful in any development process, it can also lead to confusion among policy makers and heighten a perception that conservation genetics is too abstract to be of use to organisations and governments. 3. As the developers of five of the different approaches, we have come together to explain how various approaches relate to each other and propose a scorecard, as a unifying reporting mechanism for genetic diversity. 4. Policy implications. We believe the proposed combined approach captures the strengths of its components and is practical for all nations and subnational governments. It is scalable and can be used to evaluate species conservation projects as well as genetic conservation projects., Journal of Applied Ecology, 59 (9), ISSN:0021-8901, ISSN:1365-2664

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats and, potentially, to local extinctions. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities and surrounding landscapes. Using a dataset with site-level occurrence and trait data of 5302 species from six terrestrial fauna taxonomic groups across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy consistently showing the strongest response. The effect of urbanisation on community trait composition is strongest at the largest spatial scale considered, and more closely linked to landscape composition (% urban) than arrangement (aggregation), although latitude and climatic variables remain a stronger influence. This study did not find evidence in support of a global urban taxa syndrome, but instead we suggest that there are four general urban trait syndromes, with resources associated with reproduction and diet likely to be driving patterns in traits associated with mobility and body size. Functional diversity measures showed a wide range of responses, leading to a shift in trait space that is most likely driven by the distribution and abundance of critical resources, and the urban trait syndrome displayed by individual species within a community. Further research is required to understand the interactions between the four general urban trait syndromes, resource distribution and abundance and changes in functional diversity of taxa at different spatial and temporal scales. Maximising opportunities to support species within taxa groups with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation at the taxa level, and helps ensure that urban environments have the ecological capacity to respond to challenges such as climate change, further habitat fragmentation and loss, and other disruptions. These actions are critical if we are to reframe the role of cities in global biodiversity loss.

Delivering a revolution in evidence use requires a cultural change across society. For a wide range of groups (practitioners, knowledge brokers, organisations, organisational leaders, policy makers, funders, researchers, journal publishers, the wider conservation community, educators, writers, and journalists), options are described to facilitate a change in practice, and a series of downloadable checklists are provided.

Transforming conservation depends on evidence being embedded within decision-making processes. This chapter presents general principles for embedding evidence into a wide range of approaches and processes. These include creating action plans (habitat or species), guidance documents, funding applications, policy, business environmental strategies, and management plans, as well as deciding what to fund, what to report or how to construct models. How well evidence is used in these processes can be evaluated through various processes and indices.

Processes of island colonisation have long been of interest to biologists. Colonisation events themselves are rarely observed, but the processes involved may be inferred using genetic approaches. We investigated possible means of island colonisation by common toads (Bufo bufo) in western Scotland (the Isle of Skye and five neighbouring small islands), using evidence derived from nuclear microsatellites and mitochondrial (mt) DNA. Levels of microsatellite allelic richness for populations on Skye were high and comparable to adjacent mainland populations, but lower for populations on small islands. Pairwise measures of genetic distances between populations and a clustering algorithm were both suggestive of frequent gene flow between Skye and the mainland. For small islands the levels of genetic differentiation were higher, implying stronger isolation and no evidence for inbreeding. The distribution of mtDNA haplotypes broadly mirrored the genetic structure revealed by microsatellites. Reconciled with existing palaeoclimatological evidence, since the last glaciation, our findings rule out the possibility that the B. bufo populations stem from glacial refugia, or that recent anthropogenic transfer of toads is responsible for their current distribution. The most parsimonious explanation of our data is that the studied inshore islands have been repeatedly colonised via rafting from the mainland or neighbouring islands. This may give us insights into the processes likely to take place when ice sheets retreat poleward as a result of climate change. It also has implications for the colonisation of both native and invasive non-native species, and hence the biosecurity of island refugia.

In chapter 3 of Wild Animal Ethics Johannsen argues for a collective obligation based on beneficence to intervene in nature in order to reduce the suffering of wild animals. In the same chapter he claims that the non-identity problem is merely a “theoretical puzzle” (p.32) which doesn’t affect our reasons for intervention. In this paper I argue that the non-identity problem affects both the strength and the nature of our reasons to intervene. By intervening in nature on a large scale we change which animals come into existence. In doing so, we enable harmful animals to inflict harms on other animals, and we put other animals in harm’s way. The harms that these animals will inflict and endure are foreseeable. Furthermore, since non-human animals aren’t moral agents, harmful animals cannot be morally responsible for their harmful actions. I argue therefore that by causing animals to exist, knowing that they will inflict and suffer harms, we become morally responsible for those harms. By engaging in identity-affecting actions then we take on secondary moral duties towards the animals we have thereby caused to exist, and these secondary moral duties may be extremely demanding, even more so than the initial costs of intervention. Finally, these duties are duties of justice rather than duties of beneficence, and as such are more stringent than purely beneficence-based moral reasons. Furthermore, this conclusion flows naturally from several plausible principles which Johannsen explicitly endorses.

It is a precept of commonsense morality that parents have permissions to be partial toward their own children in various ways: they are permitted to act in a variety of ways that favor the interests of (only) their own children. But how are such permissions to be reconciled with more general principles of justice? In this article, I discuss this question as it arises for one kind of liberal egalitarian theory of justice. Given their robust commitment to an ideal of equality, such theories face prima facie difficulties in accommodating the commonsense permissions of parental partiality. After sketching the contours of the apparent conflict between equality and parental partiality (§2), I survey some of the ways in which some writers have attempted to reconcile equality and parental partiality, and I criticize these reconciliation proposals, which in different ways subordinate a concern for equality to a concern for parental partiality (§3). I then suggest a different direction for reconciliation, which (conversely) subordinates a concern for partiality to a concern for equality (§4). This alternative reconciliation strategy, I argue, deserves to be taken seriously by liberal egalitarians; whether it is the most plausible way to reconcile equality and parental partiality depends on one’s view about the moral weight of people’s interest in parenting.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease. NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

“Chineseness” is often depicted in public discourses within the People’s Republic of China (PRC) as an identity that blurs together varied notions of shared cultural heritage, as well as common descent, within discourses of a unified national identity. This combines what might be called “ethnicity” (as cultural heritage), “race” (as common descent, physical or intrinsic characteristics), and “nation” (as territory and political state) in complex ways. And yet, a standard position within Chinese discourses (and often replicated in non-Chinese scholarship) is that historically informing the present, Chinese notions of “ethnic difference” are based on differences in “culture,” thus precluding “racism.” This characterization in part derives from the narrative that Chinese history was an ongoing process of “sinicization”—namely “backwards,” “barbarian” ethnic groups eagerly assimilated into the “more advanced” Han “civilization,” thus becoming “Chinese.” However, there are numerous scholarly challenges to this narrative as historically inaccurate or overly simplistic, as well as challenges to the positioning of this narrative as not “racist.” The idea that an emphasis on civilization versus barbarism is “cultural” and not “racial” delimits racism to a narrow definition focusing on “biophysical” difference. However, wider scholarship on race and racism highlights that the latter rests on diverse articulations of hierarchical difference; this includes and mobilizes cultural difference as an active part of racist discourses predicated on the acceptance of ideas of the “inferiority” versus “superiority” of peoples, as well as notions of “purity” within discourses of homogeneous imagined communities. Increasingly, “being Chinese” is being conceptualized in PRC official rhetoric as a culturally, and racially, homogeneous identity. That is, not only is Han culture being positioned as emblematic of “Chinese culture” generally but also it is being asserted that all ethnic groups are descended from the Han and are thus genetically bound by “Chinese bloodlines.” Such discourses have repercussions for ethnic minority groups within China—most clearly at the moment for Uyghurs and other Muslim minorities who are positioned as “infected” by “foreign influences,” namely their religion. This is particularly clear in the contemporary sinicization campaign in Xinjiang (XUAR: Xinjiang Uyghur Autonomous Region), a region in northwest China that has gained increasing international attention due to the government’s use of “re-education” camps in a program it argues is designed to eliminate terrorism. The accompanying sinicization campaign involves a combination of propaganda emphasizing “Chinese socialist characteristics” and “core values” that should be adopted, an emphasis in the media on Uyghurs engaging in Han cultural practices as a demonstration of their loyalty to the state, as well as the removal of many visible signs of Chinese Islamic history and Uyghur culture. The turn toward politically policing culture is hardly new in China; however, the increasing emphasis on racial notions of identity—foregrounding physical appearance, genetics, lineage, and metaphors of “bloodlines”—is an attempt to turn a national identity into a “natural” one, something that raises urgent questions with regard to how China deals with the diversity of its population and the stakes in being, or becoming, “Chinese.”

G. A. Cohen has argued that there is a surprising truth in conservatism—namely, that there is a reason for some valuable things to be preserved, even if they could be replaced with other, more valuable things. This conservative thesis is motivated, Cohen suggests, by our judgments about a range of hypothetical cases. After reconstructing Cohen's conservative thesis, I argue that the relevant judgments about these cases do not favor the conservative thesis over standard, nonconservative axiological views. But I then argue that there is a Mirrored Histories case that is such that, if one shares Cohen's conservative attitude, judgments about this case favor Cohen's conservative thesis over a wide range of non-conservative axiological views. Reflection on this case also suggests a different explanation of apparently conservative judgments that merits consideration in its own right.

BACKGROUND CONTEXT Outcomes of treatment in care of patients with spinal disorders are directly related to patient selection and treatment indications. However, for many disorders, there is absence of consensus for precise indications. With the increasing emphasis on quality and value in spine care, it is essential that treatment recommendations and decisions are optimized. PURPOSE The purpose of the North American Spine Society Appropriate Use Criteria was to determine the appropriate (ie reasonable) multidisciplinary treatment recommendations for patients with degenerative spondylolisthesis across a spectrum of more common clinical scenarios. STUDY DESIGN A Modified Delphi process was used. METHODS The methodology was based on the Appropriate Use Criteria development process established by the Research AND Development Corporation. The topic of degenerative spondylolisthesis was selected by the committee, key modifiers determined, and consensus reached on standard definitions. A literature search and evidence analysis were completed by one work group simultaneously as scenarios were written, reviewed, and finalized by another work group. A separate multidisciplinary rating group was assembled. Based on the literature, provider experience, and group discussion, each scenario was scored on a nine-point scale on two separate occasions, once without discussion and then a second time following discussion based on the initial responses. The median rating for each scenario was then used to determine if indications were rarely appropriate (1 – 3), uncertain (4-6), or appropriate (7-9). Consensus was not mandatory. RESULTS There were 131 discrete scenarios. These addressed questions on bone grafting, imaging, mechanical instability, radiculopathy with or without neurological deficits, obesity, and yellow flags consisting of psychosocial and medical comorbidities. For most of these, appropriateness was established for physical therapy, injections, and various forms of surgical intervention. The diagnosis of spondylolisthesis should be determined by an upright x-ray. Scenarios pertaining to bone grafting suggested that patients should quit smoking prior to surgery, and that use of BMP should be reserved for patients who had risk factors for non-union. Across all clinical scenarios, physical therapy (PT) had an adjusted mean of 7.66, epidural steroid injections 5.76, and surgery 4.52. Physical therapy was appropriate in most scenarios, and most appropriate in patients with back pain and no neurological deficits. Epidural steroid injections were most appropriate in patients with radiculopathy. Surgery was generally more appropriate for patients with neurological deficits, higher disability scores, and dynamic spondylolisthesis. Mechanical back pain and presence of yellow flags tended to be less appropriate, and obesity in general had relatively little influence on decision making. Decompression alone was more strongly considered in the presence of static versus dynamic spondylolisthesis. On average, posterior fusion with or without interbody fusion was similarly appropriate, and generally more appropriate than stand-alone interbody fusion which was in turn more appropriate than interspinous spacers. CONCLUSIONS Multidisciplinary appropriate treatment criteria were generated based on the Research AND Development methodology. While there were consistent and significant differences between surgeons and non-surgeons, these differences were generally very small. This document provides comprehensive evidence-based recommendations for evaluation and treatment of degenerative spondylolisthesis. The document in its entirety will be found on the North American Spine Society website ( https://www.spine.org/Research-Clinical-Care/Quality-Improvement/Appropriate-Use-Criteria) .

Youth accessing mental health care often experience a disruption in care as they attempt to transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS). Few studies have evaluated interventions seeking to improve the experience and outcomes of CAMHS–AMHS transitions, in part due to lack of consensus on what constitutes best practices in intervention success. As such, the aim of this study was to engage patients, caregivers, and clinicians to prioritize core components of successful CAMHS–AMHS transitions which can be used in the design or evaluation of transition interventions. As such, a Delphi study was conducted to determine core components of successful CAMHS–AMHS transitions. Guided by the principles of patient-oriented research, three balanced expert panels consisting of youth, caregivers, and clinicians ranked and provided feedback on the importance and feasibility of core components of CAMHS-AMHS transitions. Components endorsed as feasible or important with ≥ 70% agreement from any panel moved to the next round. As a result, a list of 26 core components of CAMHS–AMHS transitions has been refined which can be used in the design, implementation, or evaluation of interventions intended to improve transition experiences and outcomes for youth in mental health care. Youth and families were engaged in an expert advisory role throughout the research process, contributing their important perspectives to the design and implementation of this study, as well as interpretation of the findings.

Current trends in disaster response and management include various stakeholders, including non-government organisations (NGOs), volunteer groups and other humanitarian organisations, working alongside governmental agencies. Together, they are directly involved in reconstruction efforts, with support often extending from the early response to long-term reconstruction. The common goal of reconstruction efforts spanning the last few decades is the ambition to “Build Back Better”. More recently, there have been efforts to expand the scope of the reconstruction efforts to “Build Back Safer” and to raise awareness about the quality and safety of the final products, such as housing and infrastructure. Disaster management studies rarely address the construction process after disasters, or the working conditions of the builders, and often pay little attention to the health and safety of the extended workforce. This study identifies critical factors affecting workers, volunteers, local communities and other staff working on disaster reconstruction projects through a systematic literature review of academic publications. A total of 35 publications were thematically analysed, reduced from an initial selection of 394 publications selected between 2004 to 2022. The findings from this study highlight the vulnerabilities experienced by workers and the broader community involved in post-disaster reconstruction and acknowledge challenges integrating health and safety concerns into the practice and governance of global humanitarian systems.

This commentary makes the argument that constructive dialogue with China represents the only viable route for the emerging “coalition of the willing” to bring an end to the crimes against humanity ...

Clinically faithful pre-clinical models are essential for screening therapies and studying resistance mechanisms. Historically models have failed to predict response in the clinical setting. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model, employing the syngeneic, mesenchymal-NFpp10a-cell line, in both young and aged mice. We have characterised the model's response to standard of care resection and temozolomide (TMZ) treatment. We have further studied response to anti-PD1 therapy (adjuvant and neoadjuvant). NFpp10a-Luc2 expressing cells were orthotopically implanted into C57BL/6 mice (aged { > 18months} and young {6-8weeks}) and weekly bioluminescence imaging (BLI) performed to monitor tumour growth. Several therapeutic interventions were assessed to study tumour growth and survival: (1)surgical resection, (2)TMZ, (3)anti-PD1 (4)neoadjuvant anti-PD1. RNAseq, murine microenvironment cell population (mMCP) counter and gene ontology analyses characterised treatment related changed in the TME. We demonstrated survival advantage in aged mice undergoing resection (Resection:33.5 days vs Non-Resection:18 days;p=0.0166). Subsequently, we observed that TMZ and anti-PD1 monotherapy had no impact on NFpp10a-Luc2 growth (TMZ-overall:p=0.9001, and anti-PD1-overall:p = 0.7933) or survival (TMZ-overall:p = 0.3035, anti-PD1-overall:p= 0.6328). Neoadjuvant anti-PD1 treated mice demonstrated no survival advantage compared to IgG control (33-days vs 35-days:p = 0.9429). or BLI signal (p = 0.1703). NFpp10a-Luc2 forms immune-cold TME relative to commonly employed models. mMCP counter analysis demonstrates neoadjuvant anti-PD1 induced influx of CD8+-T cells, B cells, and monocytes into the TME compared to IgG control, and was associated with significantly upregulated CXCR3 chemokine receptor binding pathway on gene ontology analysis (p = 0.0045). Overall, we have, for the first time established and characterised response of the NFpp10a-Luc2-C57BL/6 model to resection, TMZ and anti-PD1 therapies. NFpp10a-Luc2 tumours demonstrate similar therapeutic resistance and TME profile compared to human mesenchymal GBM. The model may therefore be employed in future pre-clinical studies to guide clinical trials in mesenchymal GBM.

While magnetic resonance imaging (MRI) is the predominant imaging modality for glioblastoma (GBM), pre-clinical MRI scanner availability is limited. As pre-clinical CT is more widely available and cost-effective, this study aimed to 1) establish preclinical-GBM CT and CT-radiomic workflows, 2) identify whether CE-CT could detect murine orthotopic GBM tumours on two CT instruments [TRIUMPHX-O-CT; IVISSPECTRUM-CT], 3) assess whether CT-radiomic features could distinguish tumour from normal tissue, and support earlier detection of tumours, 4) verify translation of pre-clinical CT-radiomic pipelines to, and assess pre-clinical CT-features in, clinical CE-CT scans.U87R-Luc2(n=25) and NFpp10a-Luc2(n=10) orthotopic GBM models were established and tumours monitored via bioluminescence imaging (BLI). Concurrently, mice underwent CE-CT (IV-iodine/300mg/mL/50kV-scan). Extracted radiomic features (PyRadiomics) underwent dimensionality reduction (Spearman correlation; >0.85). Remaining features were analysed (Recursive feature elimination (RFE)/RepeatedCV/randomforest) in normal and tumour tissue and across timepoints (TRIUMPHX-O-CT-Wk3vsWk6,Wk6vsWk9/12; IVISSPECTRUM-CT-Wk6vsWk9/12).CE-CT and radiomic pipelines were successfully established for orthotopic GBM models, using both CT-systems. On visual assessment of images, BLI was significantly more sensitive, with tumours detectable at Wk1 (BLI) vs Wk9 (CE-CT). However, RFE analysis identified CT-radiomic features (first_order&glcm) which differentiated tumour from normal tissue (TRIUMPHX-O-CT). A subsequent feature set (first_order,glcm,gldm&glzm) were identified (TRIUMPHX-O-CT/IVISSPECTRUM-CT), detecting tumours earlier (Wk3&Wk6) than possible by visual assessment of CTs. Preclinical radiomic methods were successfully applied to exploratory clinical CE-CT scans(n=10). Here, several preclinical CT-features (e.g. Zone_Entropy) showed increased intensity in tumour regions. Overall experimental BLI is the most sensitive method for pre-clinical intracranial tumour detection. However, analysis of clinically relevant CT-radiomic features may facilitate tumour identification and earlier tumour detection (Wk3/Wk6-TRIUMPHX-O-CT/Wk6-IVISSPECTRUM-CT) than possible by visual assessment of CT (Wk9). Clinically relevant CT-derived radiomic features may therefore support intracranial rodent tumour assessment. Importantly, preclinical radiomic methods successfully translate to clinical CT-radiomic analysis. Parallel trends in tumour-specific feature intensities across pre-clinical and clinical scans suggest species conservation of features.

TGF-β is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-β blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-β type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer.This was an investigator-initiated, single-arm, phase 2 study done in two medical centres in Portland (OR, USA). Eligible patients had previously untreated, locally advanced, rectal adenocarcinoma, stage IIA-IIIC or IV as per the American Joint Committee on Cancer; Eastern Cooperative Oncology Group status 0-2; and were aged 18 years or older. Participants completed two 14-day courses of oral galunisertib 150 mg twice daily, before and during fluorouracil-based chemoradiotherapy (intravenous fluorouracil 225 mg/mBetween Oct 19, 2016, and Aug 31, 2020, 38 participants were enrolled. 25 (71%) of the 35 patients who completed chemoradiotherapy proceeded to total mesorectal excision surgery, five (20%) of whom had pathological complete responses. Ten (29%) patients had non-operative management, three (30%) of whom ultimately chose to have total mesorectal excision. Two (67%) of those three patients had pathological complete responses. Of the remaining seven patients in the non-operative management group, five (71%) had clinical complete responses at 1 year after their last modified FOLFOX6 infusion. In total, 12 (32% [one-sided 95% CI ≥19%]) of 38 patients had a complete response. Common grade 3 adverse events during treatment included diarrhoea in six (16%) of 38 patients, and haematological toxicity in seven (18%) patients. Two (5%) patients had grade 4 adverse events, one related to chemoradiotherapy-induced diarrhoea and dehydration, and the other an intraoperative ischaemic event. No treatment-related deaths occurred.The addition of galunisertib to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer improved the complete response rate to 32%, was well tolerated, and warrants further assessment in randomised trials.Eli Lilly via ExIST program, The Providence Foundation.

Objective The T-cell receptor β constant region 1 (TRBC1) antibody can identify T-cell clonality and distinguish pathological from normal T cells. This study aims to establish optimal cutpoints for establishing monotypia and validate the diagnostic abilities of the TRBC1 antibody when used as a reflex test in conjunction with an existing T-cell antibody panel. Materials and Methods We used 46 normal peripheral blood specimens and examined 8 patients with reactive lymphoproliferations to determine the normal biological range of TRBC1 on CD4+ and CD8+ T cells. We also evaluated 43 patient specimens that were submitted for investigation of a lymphoproliferative disorder for CD2/CD3/CD4/CD5/CD7/CD8/CD16/CD26/CD45/CD56/TCR αβ/TCR γδ, along with TRBC1 expression. The results were compared to TCR gene rearrangement patterns using polymerase chain reaction (PCR) analysis. Results Statistical analysis established differing cutoff points for establishing monotypia dependent on restricted TRBC1 or TRBC2 usage. Direct comparison with molecular analysis indicated that no specimen identified with the restricted expression of TRBC1 was reported as polyclonal by PCR with a concordance rate of 97% between a clonal PCR result and monotypic TRBC1 expression. Conclusion Incorporation of the TRBC1 antibody using statistically derived cutoff points in a reflex setting for the evaluation of a suspected T-cell neoplasm improves the identification of clonal T-cell populations by flow cytometry and correlates well with molecular methods.

Many egalitarians incorporate a concern for interpersonal welfare inequality as part of their favored axiology – that is, they take it to be a bad-making feature of outcomes. It is natural to think that, if inequality is in this sense a bad, it is an impersonal bad (one that makes an outcome worse, while not in itself being worse for any person). This natural thought has been challenged. Some writers claim that egalitarian judgments can be accommodated by adopting an expanded view of a person's good, according to which being worse off than others is one of the factors that, in itself, makes one's life go worse. The putatively impersonal bad of inequality is thereby “dispersed” among individuals. I argue that this dispersion strategy fails. In a slogan: if you care about inequality, do not disperse it.

Introduction Biclonal lymphoid disorders, when two distinct lymphoproliferative disorders (LPD) co-exist, are rare (incidence of 1.4%) and associated with a poor prognosis. NOTCH1 mutations occur in 10% of CLL at diagnosis, associated with a short disease-free interval and increased risk of Richter's transformation. We hypothesised that the incidence of NOTCH1 mutations in CLL with a second LPD may be increased, because the mutation occurs early in leukaemogenesis, permitting clonal divergence. Methods We identified 19 patients with biclonal LPD at diagnosis: 11 with CLL and a second LPD (group A) and 8 with a second distinct CLL (group B). NOTCH1 mutation analysis was performed and clinical outcome investigated. Results Ten of 19 (52%) were NOTCH1 mutated: 5 in group A (45%) and 5 in group B (62.5%) with a favourable clinical outcome observed among this cohort with 28.7 (range 1-99) months of follow-up. Conclusion In conclusion, we identified a significant (52%) incidence of NOTCH1 mutations in CLL in the context of biclonal LPD, associated with an indolent clinical course.

Background Adult neurosurgery in Ireland is carried out in two specialist centres, attached to only two medical schools. This leaves four Irish medical schools with no formal clinical attachment in neurosurgery. We organised a student neurosurgical conference to increase exposure to neurosurgical topics and to evaluate student's experience of undergraduate neurosurgical education. Methods The conference was organised by students from two Irish Universities with assistance from the National Neurosurgical Centre. It was open to students from all medical students in Ireland. Attendees were invited to complete a questionnaire before and after the conference. Questions were either yes or no answer or responses on a Likert scale. Results 95 students attended and all medical schools in Ireland were represented. 22% of attendees have received neurosurgical teaching during their medical education, while only 12% had a clinical rotation in neurosurgery. 40% of students are in a medical school attached to a hospital that performs neurosurgery. 54% of attendees disagreed or strongly disagreed that their medical education has comprehensively covered neurosurgical topics. 92% agreed or strongly agreed that they would like more teaching or clinical exposure in neurosurgery. 96% would attend future neurological study days. Conclusions Undergraduate neurosurgical education in Ireland varies between Irish medical schools. Many students reported their medical education has not adequately covered neurosurgical topics and that they would like more exposure to neurosurgical teaching and clinical attachments. Nearly all students reported they would attend future neurosurgical student conferences and this may be one method of increasing exposure to neurosurgery as a medical student.

PurposeThis paper analyses the incremental housing process developed at Villa Verde, a housing project designed by the Chilean architecture firm Elemental, whose director Alejandro Aravena received the Pritzker Prize in 2016. This project is conceived within a social housing framework and designed as an affordable “half-house” to be incrementally extended by the owners.Design/methodology/approachThis paper is based on research undertaken in August 2017 with data obtained through site surveys, trace analysis, interviews with 32 residents and photographic surveys. The researchers mapped the modifications made by all households at Villa Verde in the four years after occupation.FindingsThe strategy of designing a formal framework for informal additions has generally been successful with most houses undergoing substantial expansion to a high standard of construction. The paper raises concerns regarding the settlement's urban design, response to local climate and the quality of shared open space. We also find evidence of over-development as informal additions extend across front and rear yards that are in some cases fully enclosed.Originality/valueThis project is critiqued within the context of a long series of architectural attempts to harness the productive capacities of self-help housing. Villa Verde engages the freedom to build in a self-organised manner within a formal framework. But what will stop these additions from escalating into a “slum”?

In August 1992 the George H.W. Bush administration-led ‘Permanent Three’ (P3) coalition of the United States, Britain, and France announced the creation of a no-fly zone over southern Iraq, south o...

Assessments in medical education, with consequent decisions about performance and competence, have both a profound and far-reaching impact on students and their future careers. Physicians who make decisions about students must be confident that these decisions are based on objective, valid and reliable evidence and are thus fair. An increasing use of psychometrics has aimed to minimise measurement bias as a major threat to fairness in testing. Currently, there is substantial literature on psychometric methods and their applications, ranging from basic to advanced, outlining how assessment providers can improve their exams to make them fairer and minimise the errors attached to assessments. Understanding the mathematical models of some of these methods may be difficult for some assessment providers, and in particular clinicians. This guide requires no prior knowledge of mathematics and describes some of the key methods used to improve and develop assessments; essential for those involved in interpreting assessment results. This article aligns each method to the Standards for educational and psychological testing framework, recognised as the gold standard for testing guidance since the 1960s. This helps the reader develop a deeper understanding of how assessors provide evidence for reliability and validity with consideration to test construction, evaluation, fairness, application, and consequences, and provides a platform to better understand the literature in regards other more complex psychometric concepts that are not specifically covered in this article.