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Michael Weekes

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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: mpw1001@cam.ac.ukThe UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Most recent documents

Dymphna Wiegmans

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The contemporary interaction of climate and land use change drives vegetation composition and species distribution shifts, making their respective roles difficult to disentangle. In this study, we investigated long-term ruderal plant species distributions along the ‘Rallarvägen’ trail in Abisko, subarctic Sweden – a trail established for railroad construction in 1903 and paralleled by the E10 Highway (since 1982). Using vegetation and climate data from 1903, 1913, 1983, and 2021, we found that warm-adapted ruderal plant species were already common along the Rallarvägen at its initial creation at the start of the 20th century. Interestingly, however, many of these native and non-native ruderals with relatively high temperature affinity that were present in 1903 and 1913, disappeared since then and did not return, despite the substantial rise in temperature in the region over the last decades. The historical disturbances also had long-lasting effects on the current spatial distribution of the ruderal vegetation. Most ruderals still reside close to the railroad tracks and are progressively filtered out with increasing distance from anthropogenically disturbed introductory points, such as train stations, where they peak in richness – a process we coined Horizontal Directional Ecological Filtering, in parallel to the established concept of Directional Ecological Filtering along elevational gradients. We conclude that it is important to know the disturbance history of a system to get a good understanding of the long-term dynamics in the vegetation community, and thus its possible future in a changing climate.

Alain Gobert

and 14 more

Background and Purpose: Colorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as iso-levuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells from patients with CRC. We thus investigated the role of these reactive aldehydes on colon cancer development. Experimental Approach: We investigated the effect of oral treatment with 2-hydroxybenzylamine (2-HOBA), a natural compound derived from buckwheat seeds that acts as a potent scavenger of electrophiles, on colon carcinogenesis using the azoxymethane-dextran sulfate sodium model of colitis-associated carcinogenesis and mice with epithelial-specific deletion of the adenomatous polyposis coli gene, as a model of sporadic cancer. We also tested 2-HOBA in a murine xenograft of human HCT116 CRC cells implanted into the flank of nude mice. Key Results: 2-HOBA is bioavailable in the colon of mice after supplementation in the drinking water and does affect the colonic microbiome. However, it reduced the level of isoLG adducts to lysine as well as tumorigenesis in both models of CRC. In parallel, we found that NRF2 activation and signaling was decreased in the colon of 2-HOBA-treated mice. Last, the growth of human tumors is significantly attenuated by 2-HOBA supplementation. Conclusion and Implications: 2-HOBA, which has been shown to be safe in humans, reduces colon tumorigenesis and growth of tumor cells in three distinct models of CRC. Thus, 2-HOBA represents a promising natural compound for the prevention and treatment of CRC.

Chris I. Wong

and 5 more

Background: Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity – as many are infants and/or undergo nephrectomy – have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing-regimen. Procedure: Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability including kidney injury and grade 3-5 non-hematologic toxicities. Results: Fourteen patients with a median age of 1.7 years (range 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n=9) [primary renal (n=2)]; diffuse anaplastic Wilms tumor (n=3); clear cell sarcoma of the kidney (n=1); and anaplastic chordoma (n=1). All children with primary renal tumors (43%) underwent complete (n=5) or partial nephrectomy (n=1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n=5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. Conclusions: In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.

Long Li

and 5 more

A new surgical approach for nephroblastoma with a tumor thrombus in the lower vena cava reaching the right atriumDear editor:Malignant renal tumors account for 6% of all pediatric tumors, with Wilms’ tumor (WT) being the most prevalent1. Tumor emboli (TE) invade the inferior vena cava (IVC) and reach the right atrium in 5–10% of patients2. IVC thrombectomyis is a complex procedure with a surgical complication rate of 16.2–20.3%3 . Preoperative chemotherapy can reduce tumor and thrombi volumes and improve patient survival. Preoperative chemotherapy and delayed surgery are usually recommended to reduce the size/extent of the TE and minimize surgical complications4; nevertheless, TE adhesion to the vascular wall (VW) is common and can result in fracturing of thrombi and difficulty in removing emboli. The right atrium and IVC are opened and TE are removed during cardiopulmonary bypass (CPB) and deep hypothermic circulation arrest (DHCA) 5, 6. Invasion of the VW by tumor thrombi may necessitate partial resection and repair. However, this can increase intraoperative blood loss and transfusion rate and carries a risk of disseminating intravascular coagulation and tumor spread7. Small movable thrombi can be removed through a buttonhole in the vessel, while larger thrombi may require more extensive cavotomies, and adherent thrombi require partial resection/reconstruction. However, the use of bioartificial blood vessels or vascular patch materials carries a risk of thrombosis and infection, and autologous vascular transplantation can cause damage8 . As children grow, they require patch materials with growth potential. Falciform ligament (FL) is useful for repairing the IVC during liver surgery. FL is easy to obtain and adjust in size/shape. Compared to polyester/polytetrafluoroethylene, vascular repair with FL is associated with a lower risk of thrombosis and graft infection, and no risk of rejection or need for therapeutic anticoagulation9, 10.There are currently no reports on tumor thrombus (TT) removal from the IVC and right atrium without CPB and CHCA. Here, we report a novel pediatric surgical technique wherein the right atrium was incised before thrombectomy was performed without CPB and DHCA, and FL was used to repair the IVC.A 5-year-old girl was diagnosed with WT with an IVC TT. Tumor size was reduced after four cycles of the CCCG-WT-2016 chemotherapy regimen (from 11.3×8.5×12.2 cm to 3.8×5.0×6.2 cm). The patient then underwent right radical nephrectomy and thrombectomy without CPB and DHAC. An intraoperative ultrasound showed that the TT had invaded the IVC and entered the pericardium over the second hepatic hilum, moving 1.5 cm into the right atrium. (Fig. 1). The left renal vein and IVC were cut longitudinally, and the thrombi in the left renal vein, IVC, and right atrium were removed. The TT adhered to the blood vessel wall and into the surrounding branches showing drill-like growth, which was fully removed. The longest vascular occlusion time was 33 min. Continuous sutures with 4-0 silk were used to repair the blood vessels. Complete resection of the right renal tumor, perirenal fat sac, and ureter was achieved. Stenosis of the IVC blocked blood flow, and the liver was enlarged. Therefore, blood flow could not be returned to the abdominal cavity, and the patient’s blood pressure decreased to 40/30 mmHg. The diaphragm was reopened and the suture was removed from the right anterior stenosis of the IVC. The right vessel wall of the IVC was found to have been eroded by the tumor and was not amenable to suturing. A 3-cm long and 1-cm wide section of the FL of the liver was resected and used to suture the forearm of the IVC continuously with 5-0 silk to repair the VW. Upon release of the clamp the IVC filled, the blood supply was restored, and the swelling/congestion of the liver was relieved. The patient made a full recovery and was discharged 10 days later without complications. Over the next 3 years of follow-up, the patient developed normally into a healthy school-age child.Blocking the right atrium below the level of the coronary artery, below the sinoatrial node, can thus be used to open the right atrium and remove TTs without CPB or DHCA, which offers a viable new surgical protocol. Fibrosis of blood vessels and TTs caused by multiple courses of chemotherapy in the IVC, and adhesion of these TTs, can lead to thickening and brittleness of the blood vessel walls and stenosis of the lumen. This can necessitate TT removal and suturing of the VW after a longitudinal split, which can in turn lead to further stenosis of the lumen, resulting in reflux disturbance of the hepatic venous system and systemic circulatory system below the second porta hepatis. The body adapts slowly and establishes systemic collateral circulation in the process of tumor growth; therefore, the enlargement and reconstruction of the vascular segment of the IVC at the diaphragm level can solve the problem of blood return obstruction. In contrast to more rigid materials, the FL is a strong double-sided peritoneum with excellent tension resistance and smooth surfaces suitable for facing blood vessels. It is easy to obtain, its removal has no deleterious effects, and it is, therefore, an ideal material for repairing the IVC. This case demonstrates that this surgical technique is safe and effective.

Mahvish Rahim

and 7 more

Background: Human papilloma virus (HPV) vaccination prevents the development of HPV-associated malignancies. Adolescent and young adult (AYA) survivors of childhood cancers and patients with sickle cell disease (SCD) are two vulnerable patient populations who would significantly benefit from HPV vaccination. Objective: In this mixed method study we determine the HPV vaccination rate amongst the AYA SCD and childhood cancer survivor populations. We then sought to describe patient and caregiver beliefs regarding HPV vaccination. Design/Method: We performed a retrospective chart review looking at vaccination status for patients seen in our clinics in 2019. Qualitative data was then collected via audio recorded interviews. Interviews were analyzed with a thematic content approach to understand attitudes regarding the HPV vaccination. Results: We found a notable difference between the rate of HPV vaccinations and other age-appropriate vaccinations in our childhood cancers survivors and patients with SCD. Qualitative interviews found that caregivers and AYA’s relied heavily on physician, recommendations for HPV vaccination, with a preference for subspecialist recommendation. A strong recommendation from a trusted subspecialty provider would create reassurance about vaccination and reduce misconceptions and concerns for side effects in the context of a chronic illness. Conclusion: Counseling from subspecialists could have a strong impact on understanding of the HPV vaccine in the context of chronic illness. This would likely help overcome many of the barriers to vaccination that are encountered by patients with SCD or oncology survivors.

Seongsik Park

and 2 more

Ru-xing Wang

and 10 more

Background: Accumulated clinical studies utilize intracardiac echocardiography (ICE) to guide percutaneous left atrial appendage closure (LAAO), but its procedural success and safety compared to traditional transesophageal echocardiography (TEE) remain elusive. We performed a meta-analysis to compare efficacy and safety between ICE and TEE for LAAO. Methods: Studies were screened with four online databases (including the Cochrane Library, Embase, PubMed, and Web of Science) from their inception to 1 December 2022. We utilized random or fixed-effect model to synthesize the clinical outcomes. Subgroup analysis was performed to screen the potential confounding factors. Results: A total of twenty eligible studies with 3,610 atrial fibrillation patients (1,564 patients for ICE and 2,046 patients for TEE) were enrolled. Compared with TEE group, there was no significant difference in procedural success rate (RR=1.01; 95% CI: 1.00,1.02; P=0.171; I²=0.00%), total procedural time [weighted mean difference (WMD) = -5.58; 95%CI: -15.97, 4.81; P=0.292; I²=96.40%], contrast volume (WMD=-2.61; 95%CI: -12.25, 7.02; P=0.595; I²=84.80%), and fluoroscopic time (WMD=-0.34; 95%CI: −2.09, 1.41; P=0.705; I²=82.80%) in the ICE group. Subgroup analysis revealed ICE showed less contrast use than TEE in the lower proportion paroxysmal atrial fibrillation group and lower proportion hypertension. Conclusion: Our study suggests that ICE may have comparable efficacy and safety compared to TEE for LAAO.

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Selim Polat

and 3 more

Objective: The aim of this research was to elucidate the effect of deep brain stimulation on apathy, and cognitive functions in the pre and post-operative period. Materials & Methods: This study was conducted in Adana City Training & Research Hospital, Parkinson and Movement Disorders Center between January to December 2022. Individuals were evaluated by a multidisciplinary commission consisting of neurology, neurosurgery and psychiatrists. Thirty six, aged between 18–70 years who underwent Deep Brain Stimulation at the neurosurgery clinic were included in the study. Hamiltonanxiety and depression, apathy assessment, standard mini-mental test and Montreal Cognitive Assessment scales are applied to the patients. Results: The mean Apathy Score at the pre-op was 47.77±15.83 in patients who had undergone DBS operation while it was 30.83±13.59 in the post–op. This decrease was statistically significant (p<0.003) and indicated clinical improvement. The average Hamilton Anxiety scale scores at the pre–op was 11.50±5.14, and s 10.22±5.57 at the post-op with no clinical significance (p=0.28). The UPDRS-ON value was determined as 22.55±7.53 in the pre–op and 14.50±6.99 in the post–op significantly (p<0.001). UPDRS-OFF was found to be significant with pre–op 37.44±9.85, compared to post–op 23.44±7.86 (p<0.001). Conclusion: Regarding the results of this study, it was found that sub – thalamic stimulation led to stabilization of both motor and non-motor complications. Additionally DBS ameliorated apathy and Parkinson’s Disease symptoms of patients significantly. Future studies with larger sample size that focus on both pharmacological and non-pharmacological treatments might provide better clinical aspects.
This study presents the micro- and macrophysical cloud properties as a function of their surface coupling state with the sea ice during the wintertime of the MOSAiC field experiment. Cloud properties such as cloud base height, liquid- and ice water content have been previously found to have statistically distinguished features under the presence of sea ice leads (characterized by sea ice concentration, SIC) along downwind direction from the central observatory RV  Polarstern. Those findings are mainly in an increase of liquid water content, and favored occurrence of low level clouds as contrasted to situations when the clouds are thermodynamically decoupled.The present contribution is an update considering two recent developments in the liquid detection in clouds and in the detection of sea ice leads. First, radar and lidar-based cloud droplet detection approaches like Cloudnet (Illingworth et al. 2007, Tukiainen et al. 2020) using Arctic wintertime observations and applied to measurements by the Atmospheric Radiation Measurement mobile facility (ARM) instrumental suite on-board the RV Polarstern during  MOSAiC.Secondly, we explore a new sea ice lead fraction product based on sea ice divergence. Sea ice divergence is estimated from sequential images of space-borne synthetic aperture radar with a spatial resolution of 700 m. The lead divergence product, being independent of cloud coverage, offers the unique advantage to detect opening leads at high spatial resolution.Statistics for the wintertime cloud properties based on the coupling state with the sea ice concentration and sea ice lead fraction will be presented as an approach to study Arctic clouds and their interaction with sea ice.

Margaret L Duffy

and 1 more

The response of the Pacific Walker circulation (WC) to long-term warming remains uncertain. Here, we diagnose contributions to the WC response in comprehensive and idealized general circulation model (GCM) simulations. We find that the spread in WC response is substantial across both the Coupled Model Intercomparison Project (CMIP6) and the Atmospheric Model Intercomparison Project (AMIP) models, implicating differences in atmospheric models in the spread in projected WC strength. Using a moist static energy (MSE) budget, we evaluate the contributions to changes in the WC strength related to changes in gross moist stability (GMS), horizontal MSE advection, radiation, and surface fluxes. We find that the multimodel mean WC weakening is mostly related to changes in GMS and radiation. Furthermore, the spread in WC response is related to the spread in GMS and radiation responses. The GMS response is potentially sensitive to parameterized convective entrainment which can affect lapse rates and the depth of convection. We thus investigate the role of entrainment in setting the GMS response by varying the entrainment rate in an idealized GCM. The idealized GCM is run with a simplified Betts-Miller convection scheme, modified to represent entrainment. The weakening of the WC with warming in the idealized GCM is dampened when higher entrainment rates are used. However, the spread in GMS responses due to differing entrainment rates is much smaller than the spread in GMS responses across CMIP6 models. Therefore, further work is needed to understand the large spread in GMS responses across CMIP6 and AMIP models. 

Monique Weemstra

and 3 more

Root traits and functioning: from individual plants to ecosystemsFine roots, the most distal portions of the root system, are responsible for the uptake of water and nutrients by plants, represent the main type of plant tissue contributing to soil organic matter accrual, and are key drivers of mineral weathering and soil microbial dynamics (Bardgett et al. 2014). Despite the overwhelming importance of fine root traits for plant and plant community functioning and biogeochemical cycles, basic information about their ecology is lacking, particularly compared to the wealth of information developed for leaves and stems. Testing hypotheses on how root traits underlie these ecosystem processes has been particularly hampered due to (1) a paucity of systematically collected data and (2) the complexity of the relationships between root traits and root, plant and ecosystem functioning. Nonetheless, the development of the field of root ecology in the last two decades has been outstanding, in particular in the compilation of belowground trait datasets (Iversen et al. 2017), methodological root ecological handbooks (Freschet et al. 2021b), novel conceptual frameworks to describe root trait diversity (Bergmann et al. 2020), its connection with belowground plant and community function (Bardgett et al. 2014, Freschet et al. 2021a), species’ distributions (Laughlin et al. 2021), and scaling up traits from the individual root to the ecosystem level (McCormack et al. 2017). The papers that feature in this Special Issue on Root traits and functioning: from individual plants to ecosystems cover different climate regions, taxonomic and spatial scales, and a diversity of traits (Table 1) and form perfect examples of this upward moment of the belowground component in plant ecology.

Maria Hieta

and 15 more

Suoya Fan

and 7 more

Between 81º30’ E and 83ºE the Himalayan range’s “perfect” arcuate shape is interrupted by an embayment. We hypothesize that thrust geometry and duplexing along the megathrust at mid-lower crustal depths plays a leading role in growth of the embayment as well the southern margin of the Tibetan plateau. To test this hypothesis, we conducted thermokinematic modeling of published thermochronologic data from the topographic and structural embayment in the western Nepal Himalaya to investigate the three-dimensional geometry and kinematics of the megathrust at mid-lower crustal depths. Models that can best reproduce observed cooling ages suggest that the megathrust in the western Nepal Himalaya is best described as two ramps connected by a long flat that extends further north than in segments to the east and west. These models suggest that the high-slope zone along the embayment lies above the foreland limb of an antiformal crustal accretion zone on the megathrust with lateral and oblique ramps at mid-lower crustal depths. The lateral and oblique ramps may have initiated by ca. 10 Ma. This process may have controlled along-strike variation in Himalayan-plateau growth and therefore development of the topographic embayment. Finally, we analyze geological and morphologic features and propose an evolution model in which landscape and drainage systems across the central-western Himalaya evolve in response to crustal accretion at depth and the three-dimensional geometry of the megathrust. Our work highlights the importance of crustal accretion at different depths in orogenic-wedge growth and that the mid-lower crustal accretion determines the location of plateau edge.

Wasja Bloch

and 9 more

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