The Carina Nebula and Gum 31 molecular complex: II. The distribution of the atomic gas revealed in unprecedented detail

We report high spatial resolution observations of the HI 21cm line in the Carina Nebula and the Gum 31 region obtained with the Australia Telescope Compact Array. The observations covered $\sim$ 12 deg$^2$ centred on $l= 287.5\deg,b = -1\deg$, achieving an angular resolution of $\sim$ 35 arcseconds. The HI map revealed complex filamentary structures across a wide range of velocities. Several "bubbles" are clearly identified in the Carina Nebula Complex, produced by the impact of the massive star clusters located in this region. An HI absorption profile obtained towards the strong extragalactic radio source PMN J1032--5917 showed the distribution of the cold component of the atomic gas along the Galactic disk, with the Sagittarius-Carina and Perseus spiral arms clearly distinguishable. Preliminary calculations of the optical depth and spin temperatures of the cold atomic gas show that the HI line is opaque ($\tau \gtrsim$ 2) at several velocities in the Sagittarius-Carina spiral arm. The spin temperature is $\sim100$ K in the regions with the highest optical depth, although this value might be lower for the saturated components. The atomic mass budget of Gum 31 is $\sim35 \%$ of the total gas mass. HI self absorption features have molecular counterparts and good spatial correlation with the regions of cold dust as traced by the infrared maps. We suggest that in Gum 31 regions of cold temperature and high density are where the atomic to molecular gas phase transition is likely to be occurring.Comment: 20 pages, 1 table, 16 Figures, Accepted for Publication in the Monthly Notices of the Royal Astronomical Society Journa

Implementation of a Differentiated Instruction Initiative: Perspectives of Leaders

Differentiated Instruction (DI) is a framework that supports planning for diversity within K-12 classrooms. Research has grown steadily over the past 15 years that explores DI implementation, as well as beliefs and practices. Literature to date has focused heavily on the experiences of educators, with limited attention given to the role of leadership in implementing DI in schools. The current study explores the perspectives of 19 school and board-level administrators regarding the ways in which a differentiated instruction framework was implemented within their school board as well as facilitators and barriers to the implementation and uptake of the framework. Interviews revealed five themes: a) DI continuum, b) differentiated professional learning supports, c) making space for shared professional learning, d) align/integrate/embed, and e) multi-level leadership. Our findings reflect a strong belief system of most of the participants with respect to the foundations of DI as well as an understanding of effective approaches to professional learning and school change.&nbsp

1998 Fine Art Graduation Exhibition Catalogue

Fine Art ProgramFanshawe College McIntosh GalleryUniversity of Western Ontario April 16th to May 3rd., 1998 Guest Speaker: Michael P. Gibson Director: Michael Gibson Galleryhttps://first.fanshawec.ca/famd_design_fineart_gradcatalogues/1009/thumbnail.jp

European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin

Mental health in the pandemic: a repeated cross-sectional mixed-method study protocol to investigate the mental health impacts of the coronavirus pandemic in the UK.

Funder: MQ: Transforming Mental Health; Grant(s): MQBF/3INTRODUCTION: The WHO declared a global pandemic on 11 March 2020. Since then, the world has been firmly in the grip of the COVID-19. To date, more than 211 730 035 million confirmed cases and more than 4 430 697 million people have died. While controlling the virus and implementing vaccines are the main priorities, the population mental health impacts of the pandemic are expected to be longer term and are less obvious than the physical health ones. Lockdown restrictions, physical distancing, social isolation, as well as the loss of a loved one, working in a frontline capacity and loss of economic security may have negative effects on and increase the mental health challenges in populations around the world. There is a major demand for long-term research examining the mental health experiences and needs of people in order to design adequate policies and interventions for sustained action to respond to individual and population mental health needs both during and after the pandemic. METHODS AND ANALYSIS: This repeated cross-sectional mixed-method study conducts regular self-administered representative surveys, and targeted focus groups and semi-structured interviews with adults in the UK, as well as validation of gathered evidence through citizens' juries for contextualisation (for the UK as a whole and for its four devolved nations) to ensure that emerging mental health problems are identified early on and are properly understood, and that appropriate policies and interventions are developed and implemented across the UK and within devolved contexts. STATA and NVIVO will be used to carry out quantitative and qualitative analysis, respectively. ETHICS AND DISSEMINATION: Ethics approval for this study has been granted by the Cambridge Psychology Research Ethics Committee of the University of Cambridge, UK (PRE 2020.050) and by the Health and Life Sciences Research Ethics Committee of De Montfort University, UK (REF 422991). While unlikely, participants completing the self-administered surveys or participating in the virtual focus groups, semi-structured interviews and citizens' juries might experience distress triggered by questions or conversations. However, appropriate mitigating measures have been adopted and signposting to services and helplines will be available at all times. Furthermore, a dedicated member of staff will also be at hand to debrief following participation in the research and personalised thank-you notes will be sent to everyone taking part in the qualitative research.Study findings will be disseminated in scientific journals, at research conferences, local research symposia and seminars. Evidence-based open access briefings, articles and reports will be available on our study website for everyone to access. Rapid policy briefings targeting issues emerging from the data will also be disseminated to inform policy and practice. These briefings will position the findings within UK public policy and devolved nations policy and socioeconomic contexts in order to develop specific, timely policy recommendations. Additional dissemination will be done through traditional and social media. Our data will be contextualised in view of existing policies, and changes over time as-and-when policies change

Has Authorship in the Decolonizing Global Health Movement Been Colonized?

Background: Decolonization in global health is a recent movement aimed at relinquishing remnants of supremacist mindsets, inequitable structures, and power differentials in global health. Objective: To determine the author demographics of publications on decolonizing global health and global health partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs). Methods: We conducted a cross-sectional analysis of publications related to decolonizing global health and global health partnerships from the inception of the selected journal databases (i.e., Medline, CAB Global Health, EMBASE, CINAHL, and Web of Science) to November 14, 2022. Author country affiliations were assigned as listed in each publication. Author gender was assigned using author first name and the software genderize.io. Descriptive statistics were used for author country income bracket, gender, and distribution. Findings: Among 197 publications on decolonizing global health and global health partnerships, there were 691 total authors (median 2 authors per publication, interquartile range 1, 4). Publications with author bylines comprised exclusively of authors affiliated with HICs were most common (70.0%, n = 138) followed by those with authors affiliated both with HICs and LMICs (22.3%, n = 44). Only 7.6% (n = 15) of publications had author bylines comprised exclusively of authors affiliated with LMICs. Over half (54.0%, n = 373) of the included authors had names that were female and female authors affiliated with HICs most commonly occupied first author positions (51.8%, n = 102). Conclusions: Authors in publications on decolonizing global health and global health partnerships have largely been comprised of individuals affiliated with HICs. There was a marked paucity of publications with authors affiliated with LMICs, whose voices provide context and crucial insight into the needs of the decolonizing global health movement

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.Boston UniversityPublished versio

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival