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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: 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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Weiwei Chen

and 10 more

Jiachun Sun

and 9 more

Background: Recently,epidermal growth factor receptor (EGFR) -targeting drugs have benefited thousands of patients with EGFR mutation-positive (EGFR MUT+) non-small-cell lung cancer (NSCLC). Nevertheless, nearly all patients with NSCLC who were sensitive to first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), finally developed resistance. Therefore, numerous clinicians have focused on improving the clinical effect of first-generation EGFR-TKIs (1st-gen EGFR-TKIs). Methods: To analyze the therapeutic outcomes of individuals with progressive NSCLC, a retroactive assessment was performed on 86 patients who were medicated with only icotinib or combined with pemetrexed and platinum-based chemotherapy at The First Affiliated Hospital of Henan University of Science and Technology (HAUST). Results: Eighty-six patients with NSCLC-bearing EGFR-sensitive mutations were retroactively analyzed. The results showed statistical significance in PFS (P = 0.049) and disease control rate DCR (P = 0.031) between icotinib + chemotherapy and icotinib alone, especially in the brain metastases (P = 0.021) and L-858R mutation subgroups (P = 0.05). According to the findings of the multivariate analysis, treatment (P = 0.033) and EGFR mutation status (P = 0.019) were significant predictive variables. The OS comparison between icotinib + chemotherapy and icotinib alone were not significantly different. The study included a total of 1242 patients, of which 648 obtained combined treatment and 594 obtained first-generation EGFR-TKI monotherapy. Analyzing the relevant data from multiple studies, the results showed significant improvements in ORR (RR: 0.63, 95% CI: 0.49–0.82, P = 0.0006), PFS (RR: 0.61, 95% CI: 0.47–0.79, P = 0.0002), and OS (RR: 0.67, 95% CI: 0.51–0.88, P = 0.004) for those on combination therapy. However, there was also an increase in treatment-emergent AEs among these patients. Conclusion: In summary, administering first-generation EGFR-TKI concurrently with chemotherapy provides an edge in the therapeutic management of locally or severely advanced NSCLC that is EGFR-positive. Therefore, EGFR mutation-positive NSCLC (EGFR MUT+ NSCLC) patients in this condition may find it advantageous to consider using 1st-gen EGFR-TKIs in conjunction with chemotherapy (1st-gen EGFR-TKIs + Chemo).

Pugazhendi Inban

and 6 more

IntroductionMultiple sclerosis is an infrequent inflammatory disease of the central nervous system (CNS) that is distinguished by its assorted clinical and radiological presentations [1, 2]. Tumefactive demyelination, or tumefactive multiple sclerosis, stands apart as a distinctive entity within this spectrum. Demyelinating lesions in the central nervous system (CNS) are a sign of these diseases. These lesions can be big, measuring 2 cm or more in diameter, or small, measuring between 0.5 cm and 2 cm, but have the potential to cause mass effects. This unique feature may result in these lesions being initially misidentified as tumor-like space-occupying lesions; however, they typically exhibit a characteristic appearance on radiographic imaging and are clinically benign [3–5]. Tumefactive demyelination, which is distinct from multiple sclerosis, occurs at an estimated rate of about 1-2 per 1000 cases of MS, although some studies propose a higher incidence ranging from 1.4% to 8% [6–7]. However, tumefactive demyelinating lesions can occur concurrently with autoimmune diseases (e.g., Sjogren disease, lupus erythematosus, neuromyelitis optica), infectious diseases (e.g., HIV), malignancy (e.g., renal cell carcinoma), drug-related conditions (e.g., tacrolimus, fingolimod), and postinfectious conditions (e.g., acute disseminated encephalomyelitis, acute hemorrhage leukoencephalitis). Tumefactive demyelination can show up on its own at the start of a disease or as other diseases progress, but the pathophysiology of how it happens is not well understood. On magnetic resonance imaging (MRI) scans, these lesions can appear either as a single large lesion or several lesions exhibiting varying degrees of contrast enhancement. We present here a case study involving a thirty-year-old female who presented with a fever lasting three days followed by Wernicke’s aphasia without right-sided weakness and whose MRI findings were consistent with tumefactive brain demyelination.

Gordon Younkin

and 7 more

Like other members of the Brassicaceae, plants in the wallflower genus (Erysimum) produce glucosinolates, which are potent defenses against a wide range of herbivores. As a more recently evolved second line of defense, Erysimum produces cardiac glycosides, which are allosteric inhibitors of Na+,K+-ATPases in animals. Cardiac glycoside biosynthesis has evolved in diverse lineages including foxglove (Digitalis, Plantaginaceae) and milkweeds (Apocynaceae), but the full biosynthetic pathway has not been described in any species. We identify and generate CRISPR/Cas9 knockouts of two cytochrome P450 monooxygenases involved in cardiac glycoside biosynthesis in wormseed wallflower (Erysimum cheiranthoides L.): EcCYP87A126, which cleaves the side chain from sterol precursors to initiate cardiac glycoside biosynthesis, and EcCYP716A418, which has a role in cardiac glycoside hydroxylation. In the EcCYP87A126 knockout lines, cardiac glycoside production is eliminated, effectively reversing Erysimum’s escape from herbivory. For the generalist herbivores green peach aphid (Myzus persicae Suzler) and cabbage looper (Trichoplusia ni Hübner), cardiac glycosides appear to be largely redundant with glucosinolates, having some effect in choice assays but little to no effect on insect performance. By contrast, the crucifer-feeding specialist cabbage butterfly (Pieris rapae L.), which will not oviposit or feed on wildtype E. cheiranthoides, is able to complete its life cycle on cardenolide-free E. cheiranthoides mutant lines. Thus, our study demonstrates in vivo that cardiac glycoside production allows Erysimum to escape from a specialist herbivore.

Qing-Lin Meng

and 10 more

Ecological divergence due to habitat difference plays a prominent role in the formation of new species but the genetic architecture during ecological speciation and the mechanism underlying phenotypic divergence remain less understood. Two wild rice species (O. rufipogon and O. nivara) are a progenitor-derivative species pair with ecological divergence and provide a unique system for studying ecological adaptation/speciation. Here, we constructed a high-resolved linkage map and conducted a quantitative trait locus (QTL) analysis of 19 phenotypic traits using an F2 population generated from a cross between the two wild rice species. We identified 113 QTLs associated with interspecific divergence of 16 quantitative traits, with effect sizes ranging from 1.61% to 34.1% in terms of the percentage of variation explained (PVE). The distribution of effect sizes of QTLs followed a negative exponential, suggesting that a few genes of large effect and many genes of small effect were responsible for the phenotypic divergence. We observed 18 clusters of QTLs (QTL hotspots) on 11 chromosomes, significantly more than that expected by chance, demonstrating the importance of coinheritance of loci/genes in ecological adaptation/speciation. Analysis of effect direction and v-test statistics revealed that interspecific differentiation of most traits was driven by divergent natural selection, supporting the argument that ecological adaptation/speciation would proceed rapidly under coordinated selection on multiple traits. Our findings provide new insights into the understanding of genetic architecture of ecological adaptation and speciation in plants and helps effective manipulation of specific genes or gene cluster in rice breeding.

Eben Gering

and 7 more

Recent work indicates that feralisation is not a simple reversal of domestication, and therefore raises questions about the predictability of evolution across replicated feral populations. In the present study we compare genes and traits of two independently established feral populations of chickens (G. gallus) that inhabit archipelagos within the Pacific and Atlantic regions to test for evolutionary parallelism and/or divergence. We find that these two feral populations share close genetic similarities despite the lack of any current gene flow between them. Next, we used genome scans to contrast the targets of feralisation (selective sweeps) between the two independently feral populations from Bermuda and Hawaii. Three sweep loci (each identified by multiple detection methods) were shared between feral populations, and this overlap is inconsistent with a null model in which selection targets are randomly distributed throughout the genome. In the case of the Bermudian population, many of the genes present within the selective sweeps were either not annotated or of unknown function. Of the nine genes that were identifiable, five were related to behaviour, with the remaining genes involved in bone metabolism, eye development, and the immune system. Our findings suggest that a subset of feralisation loci (i.e. genomic targets of recent selection in feral populations) are shared across independently-established populations, raising the possibility that feralisation involves some degree of parallelism or convergence. A clearer understanding of whether these reflect selection for similar functional traits (‘feralisation syndromes’) will require elucidating genotype-phenotype relationships in any populations being compared.

Farhad Mahmoudi

and 3 more

Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing remitting multiple sclerosis; A case report Farhad Mahmoudi1*, Sayed Ali Emami1, Farid Masaeli1, Najmeh Rayatpisheh21 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran2School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, IranCorresponding author*Farhad MahmoudiSchool of Medicine,Isfahan University of Medical Sciences,Isfahan, IranEmail: farhad.mg116@gmail.comAbstract: This case report presents a 58-year-old woman with Multiple Sclerosis (MS) who developed petechiae and epistaxis, rare side effects following Alemtuzumab treatment. While these reactions are infrequent, heightened awareness among healthcare providers is essential as Alemtuzumab gains popularity in MS treatment. Recognizing and managing such hypersensitivity reactions promptly is crucial for improved patient care. 1.Introduction Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system. The course of the disease varies among individuals, leading to a wide range of symptoms and patterns of presentation. Additionally, there are other conditions, such as radiologically isolated syndrome, which can progress to MS(1). While there is no curative therapy for this condition, certain drugs can modify the course of the disease and improve the prognosis and quality of life for patients.Disease-modifying treatments (DMTs) are the preferred treatment option for patients with MS. Alemtuzumab is an intravenously administered DMT drug that has been available since 2014 for the treatment of patients with multiple sclerosis who have not responded adequately to two or more DMTs. It is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the CD52 antigen on B and T lymphocytes, depleting them from the bloodstream. This drug has been described as a safe and effective treatment with minimal side effects for patients with relapsing-remitting multiple sclerosis.(2)While there are few studies on the cutaneous adverse effects of Alemtuzumab, in this study, we report the first case of an MS patient treated with Alemtuzumab who developed drug-induced petechiae and epistaxis.2. Case presentationA 58-year-old Caucasian woman with relapsing-remitting multiple sclerosis, who had no previous medical conditions, presented to the emergency department due to muscle spasms and stiffness in her right foot. Neurological examination revealed weakness in her right lower limb with 3/5 muscle strength. She was diagnosed with MS at the age of 26 through an MRI and had previously been on weekly Interferon-beta (IFNb) treatment. During acute MS attacks, she received intravenous corticosteroids. Despite being on disease-modifying therapies (DMTs), she experienced more relapses in the last year, and her Expanded Disability Status Scale (EDSS) was 3. During the current hospitalization, the patient underwent brain and cervical spinal MRI, which revealed the appearance of new periventricular white active plaques in addition to previous black old lesions.Considering the progression of her disease condition, she was started on treatment with Alemtuzumab at a dose of 12mg/day IV. There were no drug reactions, and after completing the treatment, her muscle spasms and stiffness resolved, and the patient was discharged from the hospital.The day after, the patient came to the hospital to receive the second dose of the drug. While receiving the treatment, her condition remained stable, and she did not experience any notable symptoms. However, one day after finishing the first dose, the patient started to experience a gradual appearance of petechiae on her upper and lower limbs, chest, shoulders, and back. Moreover, a few minutes later, she developed epistaxis. Her blood pressure and heart rate were 127/73 and 87, respectively. The patient denied any previous history of eczema, skin issues, or respiratory allergies.Dermatology was consulted to investigate the possible causes of petechiae, and ENT was consulted to manage and evaluate the epistaxis. Despite applying pressure to the nostrils and placing ice on the forehead, the epistaxis did not cease. Consequently, the patient underwent posterior nasal packing, which successfully halted the bleeding.

Chibuzo Ilonze

and 8 more

Background: Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease. Methods: Therefore, we conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥ 2.5 m/s and its associations with renal and cerebrovascular outcomes in children with SCD 1-21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical and Research Intervention Program (SCCRIP) cohort at St. Jude Children’s Research hospital. We hypothesized that patients with sickle cell disease with elevated TRV would have higher odds of having either albuminuria or cerebrovascular disease. Results: We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiography. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (OR 1.88 (95% CI: 1.12- 3.15)) and persistent albuminuria (OR: 1.81 (95% CI: 1.07– 3.06)) after adjusting for age, sex, treatment, and site. Conclusion: This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.

Merve Selcuk

and 18 more

Background: Previously, Cystic Fibrosis (CF) patients faced a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. Methods: The aim of this project was to implement the CF R.I.S.E. program, a structured transition program, in a CF center with limited resources at Marmara University. The program was adapted and translated into Turkish with the permission of the Cystic Fibrosis Foundation. A multidisciplinary team collaborated in the translation and adaptation process and educational materials were developed for patients and families. Results: Successful implementation of the CF RISE program was achieved within six months. A pilot study with randomly selected patients revealed positive feedback indicating the effectiveness and understandability of the program. The program facilitated strong collaboration between pediatric pulmonologists, CF nurses, dietitians and patient representatives. However, challenges were encountered due to the lack of a designated social worker, which affected patients’ access to expert guidance on social security and disability rights. Conclusions: The CF S.O.B.E. program was successfully adapted and implemented at the Marmara University CF Center in Turkey. The program is expected to have a positive impact on patients’ knowledge and self-care skills over a period of 1.5 years. It is aimed to make the program a routine practice in the center and to expand the collaboration with adult clinics. Further studies are needed to assess its long-term impact and applicability in different health settings. The ultimate goal is to disseminate the program’s resources and promote structured transition practices nationwide.

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Gizem Koken

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Background: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests (SPTs) were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: Seventy-eight patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in %16.7 of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

Shen Shen

and 3 more

Optimizing the spatial configuration of diverse best management practices (BMPs) can provide valuable decision-making support for comprehensive watershed management. Most existing methods focus on selecting BMP types and locations but neglect their implementation time or order in management scenarios, which are often investment-restricted. This study proposes a new simulation-optimization framework for determining the implementation plan of BMPs by using the net present value to calculate the economic costs of BMP scenarios and the time-varying effectiveness of BMPs to evaluate the environmental effectiveness of BMP scenarios. The proposed framework was implemented based on a Spatially Explicit Integrated Modeling System and demonstrated in an agricultural watershed case study. This case study optimized the implementation time of four erosion control BMPs in a specific spatial configuration scenario under a 5-year stepwise investment process. The proposed method could effectively provide more feasible BMP scenarios with a lower overall investment burden with only a slight loss of environmental effectiveness. Time-varying BMP effectiveness data should be gathered and incorporated into watershed modeling and scenario optimization to better depict the environmental improvement effects of BMPs over time. The proposed framework was sufficiently flexible to be applied to other technical implementations and extensible to more actual application cases with sufficient BMP data. Overall, this study demonstrated the basic idea of extending the spatial optimization of BMPs to a spatiotemporal level by considering stepwise investment, emphasizing the value of integrating physical geographic processes and anthropogenic influences.

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