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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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Most recent documents

Tawanda P. Makopa

and 6 more

Ntšhe, a Setswana name for sweet reeds, a sweet sorghum variety ( Sorghum bicolor (L)) is a commercial crop consumed as a delicacy in enormous quantities in Botswana and in southern Africa at large. Pre and post-harvest losses due to infestation by larval stages of stem borer moths, Chilo partellus often lead to severe financial losses as consumers condemn the worm-infested sweet reeds as unpalatable, “ Mo gase ntšhe tota tota” (this is not a sweet reed). Valorisation of condemned sweet reeds is one attractive route to reduce economic losses. Here, we took advantage of our understanding of yeast-insect interactions to isolate yeasts associated with larval stages of the stem borer moths and investigated their potential for production of an alcoholic sweet reed beverage. We isolated 33 yeast strains representing from the galleries and frass as well as from the guts of the larval moths. Assessment of their ability to ferment the simplest sugar, glucose, resulted in identification of 14 strains belonging to Hanseniaspora and Candida genera. These strains were further assessed for their capacity to ferment by calculating the rate of accumulation of carbon dioxide and ethanol when grown in the principal sugars found in sweet sorghum juice as sole carbon sources as well in sweet sorghum juice. In addition, as an industrially relevant trait, we tested the potential of the strains to tolerate brewing/fermentation-associated stresses. Furthermore, we assessed the aromatic complexity of the produced beverage. Our results suggest that non-conventional yeasts associated with the larval moths have potential for valorization of condemned sweet sorghum stalks to produce a sweet sorghum beverage.

Regina Demlova

and 16 more

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine result from emergency medical services showed that some creatinine results apparently deviated from expected creatinine values implying occurrence of drug-related interferences. Methods: Real-time head-to-head clinical evaluation of an enzyme method (Roche CREP2) in comparison to Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023 we analyzed 8498 patient specimens where 5524 were heavily medicated STAT patient specimens, 500 were pediatric specimens and 2474 specimens were from a distant general population in a different region using the same methods. Results: About 5 percent of hospital specimens having patient history showed apparent drops of creatinine concentrations by the enzyme method against the compensated Jaffé method. Suspect medication was found in 43 out of 46 reviewed patients where medication data were allowed for review. A general patient cohort showed no drops of concentrations measured by the enzyme method. Pediatric hospital cohort showed 6 drops out of 500 total measurements. Conclusions: Pharmacotherapy-induced inaccuracies with enzyme creatinine methods imply the need for proper method validations in the relevant patient population such as emergency hospital setting and may facilitate introduction of cystatin C to emergency medicine clinical practice as suitable creatinine alternate biomarker.
Objectives: To determine obstetrical complications in the first ongoing pregnancy following surgical management of women with Asherman syndrome (AS) Design: A cohort study conducyed between January 2010 and December 2020 with a minimal follow-up of 1 year. Setting: Study was conducted in the Asherman Expertise Center a referral center for women with AS. Population: women with a pregnancy and delivery after hysteroscopic adhesiolysis for AS Methods: Obstetrical outcomes were assessed using a follow up questionnaire and obstetrical complications data on the delivery were collected from the patients’ hospital records. Mean Outcome Measures: Obsterical outcome in women with AS such as premature delivery, small for gestational age placenta complications postpartum problem. Results: We included 425 patients with a first pregnancy of at least 20 weeks after AS treatment. 407 living children were born, and there were 16 perinatal death (including 1 set of twins, 3.3%) and 2 terminations of pregnancy (0.5%). Of these women 21.8 % had a premature delivery, 17% had a baby who was small for gestational age. Of all women, 17.8% had a placenta complication and 50.6 % had a postpartum problem. These numbers were worse among women who had a postpartum procedure as a cause of AS, as 83% of them had postpartum complications, 33% a premature delivery and 27% placenta complications. Overall, 53% of women with a first trimester procedure and 85% of women with a postpartum procedure preceding AS had a severe adverse obstetric outcome. Conclusions : After successful adhesiolysis of women with AS, pregnancy should be considered medium to high risk for complications during pregnancy and postpartum, especially among women who had a postpartum procedure in their medical history.

Yana Halmans

and 7 more

Objective: To investigate Colony-Forming Unit (CFU) reduction on contaminated flexible endoscopes without a working channel after UV-C light disinfection compared to the current disinfection method with the Endoscope Washer Disinfector. Design, setting: After pharyngolaryngoscopy, a manual pre-cleaning with tap water was performed. A culture was then collected by rolling the distal 8-10 cm of the flexible endoscope over an Agar plate. The flexible endoscope was disinfected using the D60 (60-second disinfection process with UV-C light) or the Endoscope Washer Disinfector (golden standard reprocessing process with water and chemicals). Another culture was then taken. After incubation, a CFU count was performed. Results: Two hundred flexible endoscopes without a working channel were divided equally between the two disinfection groups. After clinical use and manual pre-cleaning, 84 of the 100 (84.0%) (UV-C light group) and 79 of the 100 (79.0%) (EWD) flexible endoscopes were contaminated with at least 1 CFU. Flexible endoscopes that showed no contamination after use were excluded from further analysis. After disinfection with UV-C light, 72 (85.7%) flexible endoscopes showed no contamination (i.e. 0 CFUs) versus 66 (83.5%) flexible endoscopes after reprocessing with the Endoscope Washer Disinfector. Conclusion: There is no difference in CFUs reduction on contaminated flexible endoscopes without a working channel between UV-C light disinfection and the current gold standard, the Endoscope Washer Disinfector.
Background The treatment strategy for latent tuberculosis (TB) infection (LTBI) aims to promote a reduction in the number of cases that develop into TB and, consequently, a reduction in the transmission of pathogenic bacteria. Objectives The objective was to know the safety, effectiveness and adherence of the use of INH in two pharmaceutical presentations (300mg or 100mg tablet) reported in scientific studies. Methods A review protocol was registered a priori with PROSPERO (number CRD42020176694). The electronic databases Cochrane; PubMed; Embase; LILACS, Scopus, and Web of Science were searched for studies on use of INH for LTBI. The results and methods were presented in line with the PRISMA guidelines, and the methodological quality of the included reviews was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results Most of the studies used isoniazid (H) as a treatment for LTBI, with a duration of 9 months. There was significant variation in the of use of isoniazid, ranging from 0.3% to 98.6% of the participants. A similar variation was found in the 52 studies that similarly presented the rate of adherence to treatment with H, which ranged from 18% to 100% among study participants completing INH treatment for LTBI. In studies, the adverse events reported most frequent events reported were included hepatotoxicity, gastric intolerance, and neuropathy, the rates of occurrence of these with isoniazid, rang from < 1% to 48%. In the studies that evaluated effectiveness of isoniazid for latent tuberculosis infection, a variation from 0 to 19.7% of people who did not have active TB after the follow-up period was observed, with the highest rate among HIV-positive individuals. Conclusion Our findings indicate that isoniazid is being widely used in the world as a prophylactic treatment for tuberculosis, rates of adherence to isoniazid were above 50%. It is important to emphasize the importance of keeping the follow-up of the person who uses isoniazid due to the risk of developing unwanted events resulting from the drug. Even with treatment challenges, we identified low rates of people who used isoniazid and developed active tuberculosis during the period they were followed. We believe that isoniazid continues to contribute to tuberculosis control in the world and better care actions are needed.

Mauricio Herrera

and 5 more

INTRODUCTIONTrisomy 9 is a rare genetic alteration that represents 2.7% of all trisomies. (1,2,7) It was reported for the first time in 1973 by Feingold and Atkins, through the study of lymphocytes in the blood of a male newborn, with multiple congenital anomalies (4,5). Complete gain of chromosome 9 has a fatal prognosis and usually results in first trimester miscarriage. (2) However, in exceptional cases, pregnancies that reach term die in the early neonatal period (4).From the cytogenetic point of view, cases of trisomy 9 present completely, which is not mosaicism, or in a state of mosaicism. The spectrum of this syndrome, in addition to trisomy 9, includes partial trisomies of the short arm 9p, of the long arm 9q, mosaicisms, mosaicisms confined to the placenta and pseudo mosaicisms. (4,5). In the case of trisomy 9, most correspond to de novo mutations. Mosaicisms are related to balanced rearrangement mutations (5). However, phenotypic heterogeneity, as well as the incidence and severity of associated malformations, are directly related to the variable size of the duplicated segment and the frequent concomitant monosomy (2,3,4,6).Most of the cases of trisomy 9 reported in the literature occurred in women under 35 years of age, which makes evident the usefulness of screening for congenital anomalies, even in low-risk populations (1,2). Fetal screening in the first and second trimesters allows early detection of fetal structural abnormalities associated with genetic alterations. In this way, it offers the opportunity to advise the patient, with the aim of carrying out early interventions regarding the prenatal prognosis and postnatal management, even if it is available and for this specific case, the interruption of the pregnancy. (1)(6).This chromosomal abnormality is characterized by a constellation of multiple phenotypic abnormalities that mainly involve craniofacial, central nervous system, cardiovascular, musculoskeletal, and genitourinary abnormalities (1,4,5,7). The main structural anatomical alterations include, for ultrasound screening at 11-13.6 weeks, an increase in the thickness of nuchal translucency (1), then microcephaly and brachycephaly become evident, fontanelles and wide cranial sutures, bulbous nose, lip and cleft palate, short nasolabial fold , hypertelorism, micro-retrognathia, short and wide neck and low implantation of the ears. In the central nervous system, it is common to find associated Dandy Walker Malformation characterized by hydrocephalus, alterations in the development of the cerebellar vermis and ventriculomegaly (4,2). At the cardiovascular level, it is common to find ventricular septal defects, cardiomegaly, valvular dysplasia or even the right aortic arch. Regarding the musculoskeletal system, camptodactyly, clubfoot , hypoplasia or agenesis of the fingers and nails of the hands and feet (4), and dislocation of the hip or knees can be found. In genitourinary organs, horseshoe kidney, renal hypoplasia or dysplasia as well as renal cysts, short penis or bicornuate uterus become evident . Other case reports include abnormal lung lobulation, malrotation, hypoplasia or agenesis of the gallbladder and biliary tract, and hypoplasia of the adrenal gland. In addition, this pathology incorporates within its recognition pattern growth restriction, low birth weight and delayed neurological development. (2,7) Other authors mention that, when faced with elevated serum levels of alpha-fetoprotein in the context of trisomy 9, the finding of spina bifida should be ruled out (1). Serum markers such as the free fraction of BhCG and PAPP-A are found to be decreased in concentration in trisomies 9 and 18. In addition, different abnormal phenotypic findings overlap in both chromosomopathies; however, the genetic study can discern the final diagnosis (1,4).

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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.

Niels Fraehr

and 3 more

High computational cost is often the most limiting factor when running high-resolution hydrodynamic models to simulate spatial-temporal flood inundation behaviour. To address this issue, a recent study introduced the hybrid Low-fidelity, Spatial analysis, and Gaussian Process learning (LSG) model. The LSG model simulates the dynamic behaviour of flood inundation extent by upskilling simulations from a low-resolution hydrodynamic model through Empirical Orthogonal Function (EOF) analysis and Sparse Gaussian Process (Sparse GP) learning. However, information on flood extent alone is often not sufficient to provide accurate flood risk assessments. In addition, the LSG model has only been tested on hydrodynamic models with structured grids, while modern hydrodynamic models tend to use unstructured grids. This study therefore further develops the LSG model to simulate water depth as well as flood extent and demonstrates its efficacy as a surrogate for a high-resolution hydrodynamic model with an unstructured grid. The further developed LSG model is evaluated on the flat and complex Chowilla floodplain of the Murray River in Australia and accurately predicts both depth and extent of the flood inundation, while being 12 times more computationally efficient than a high-resolution hydrodynamic model. In addition, it has been found that weighting before the EOF analysis can compensate for the varying grid cell sizes in an unstructured grid and the inundation extent should be predicted from an extent-based LSG model rather than deriving it from water depth predictions.

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