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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: [email protected] 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.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: [email protected]

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    [email protected],  [email protected]

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.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

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.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

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.

INTRODUCTIONThe diagnosis of UTUC has always presented challenges due to the limitations of available diagnostic tools. Cytology, CTU, and URS with biopsies can all yield inadequate results, leading to false negatives. To minimize the risk of biased diagnosis, a combination of these examinations is essential. The European Association of Urology (EAU) recommends the use of diagnostic ureteroscopy and biopsy when imaging and cytology alone are insufficient for accurate diagnosis and risk stratification of the tumor (1). Similarly, according to the guidelines provided by the American Urological Association (AUA), patients with suspected UTUC should undergo evaluation using diagnostic ureteroscopy. During this procedure, any identified lesion should be biopsied, and cytologic washing from the inspected upper tract system should be performed (2).Regrettably, despite the recommendations and guidelines in place, UTUC is frequently underestimated during pre-operative diagnosis. This underestimation can have serious consequences, leading to delayed or inadequate treatment and contributing to significant mortality rates.

A document by Maria Memon. Click on the document to view its contents.

Title: Remarkable improvement of symptoms and signs of severe dry eye treated by ocular immersion hydrotherapy Yong Tao*, M.D., Haoran Cui, M.D., Shuang Zhang, M.D., Tao Zhang, M.D.Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. ChinaCorresponding author: Prof. Yong Tao, Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University; No. 8, South Road of Worker’s Stadium, Chaoyang District, Beijing 100020, China. Phone: +86-10-85231405. Fax: +86-10-85231405. E-mail: [email protected] Words: Dry eye disease; Ocular immersion hydrotherapy; Ocular graft-versus-host disease; Corneal epithelial cell damage; Ocular surface inflammation

Commentary:

Habitat suitability assessment is crucial for the conservation of endangered species in the context of dramatic global climate change. To investigate changes in the distribution pattern of forest musk in China, the present study used the optimized MaxEnt model of the ENMeval language package to simulate changes in potential suitable areas and potential suitable areas for four shared socio-economic pathways of the endangered species, forest musk (Moschus berezovskii), in both the current and the future periods, and the migration trends of the four shared socioeconomic paths in the current and future periods are analyzed. The results showed that: the MaxEnt model reached the optimal solution when RM=3.4 and FC was LQH; the dominant environmental factors for the distribution of Linnaeus musculus in China were annual precipitation, slope, and cold-season average air temperature; the current suitable habitat accounted for 23.02% of the total area of the study area, which was mainly distributed around the Hengduan Mountain Range, the area around the Longmenshan to Daliangshan Mountains, and the Qinling Mountain System; Under the future climate change, the expansion area of the suitable area is larger than the loss area, and the center of mass of the suitable area has a tendency to migrate to the northeast, in which the fluctuation area of the suitable area is smaller under the SSP370 climate scenario. Critical habitat accounts for 20.04% of the current potential suitable area, which is mainly distributed in the mountain range at the junction of Yunnan-Tibet, the junction of the Zhongshan vein and Sichuan Basin, and the Qinling mountain system. This study suggests focusing on the Yarlung Tsangpo Grand Canyon and Tsatsum Tsibagou in Tibet and the fragmented habitat of forest musk in Cangshan Erhai, Yunnan, to improve the information construction and increase the protection efforts.

In fermentation of filamentous fungi, selecting suitable impellers and controlling fungal morphology are crucial for product yield. Previously, we revealed the AGΔ-GAGΔ strain of Aspergillus oryzae, lacking both α-1,3-glucan (AG) and galactosaminogalactan (GAG), showed improved hyphal dispersion, reduced culture viscosity, and increased recombinant protein production. Here, we used computational fluid dynamics (CFD) to explore the importance of impeller selection. High-performance impellers (HS100/HR100) were compared with the conventional flat-blade turbine and flat-blade paddle combination (6FT/4FP). CFD analysis using viscosity data of the wild-type strain showed gas cavities formed behind the 6FT/4FP blades, with flow velocities and shear stresses concentrated around the impellers; in contrast, HS100/HR100 displayed a broader and more evenly spread range of flow velocities and shear stress values. CFD analysis comparing the mixing properties of AGΔ-GAGΔ and wild-type strain cultures agitated by HS100/HR100 demonstrated that slipping occurred at the impeller periphery–wall boundary in the wild-type culture, while AGΔ-GAGΔ exhibited a wide shear stress distribution and reduced gas cavity formation. The simulation results agreed well with measured volumetric oxygen mass transfer coefficient ( KLa) and mixing time. These findings suggest that an appropriate stirring system, combined with the AGΔ-GAGΔ strain, can drastically improve the mixing characteristics in filamentous fungal fermentation.

Purpose: This scoping review contributes to understanding the utilization of end-of-life anticancer drugs in gastrointestinal cancer patients, a topic posing significant public health challenges due to its prevalence, impact on morbidity and mortality, and associated healthcare costs. Insight into unique treatment patterns at the end of life is vital for enhancing the appropriateness of cancer care for these patients. Methods: Extensive searches were conducted in Medline and Embase to locate articles on the use of anticancer drugs in the end-of-life phase of gastrointestinal cancer patients. Results: We identified 30 publications and described treatment frequencies alongside methodological characteristics. On average, 7.0% and 13.2% of patients received anticancer drugs in the last two and four weeks of life, respectively, with 3.3% commencing new anticancer regimens in the final four weeks. Conclusion: This review offers a comprehensive overview of primary studies reporting end-of-life treatments in gastrointestinal cancer patients. However, methodological inconsistencies present significant challenges, highlighting a notable proportion of patients potentially experiencing overtreatment. Therefore, there is a pressing need for more standardized research methods to ensure robust evaluations and enhance the quality of care for these patients.

This study presents a novel framework This study proposes a new framework for evaluating the performance of distribution networks using a comprehensive approach. This method combines Principal Component Analysis (PCA) for extracting key performance indicators, Improved Analytic Hierarchy Process (IAHP) for determining objective weights of these indicators, and CRITIC method for determining subjective weights. Then, aggregate weights are used to calculate the comprehensive performance score of each part of the distribution network. On the premise of reducing computing resources, K-means clustering analysis is applied to classify the status of distribution network projects, providing data reference for project maintenance and repair. Finally, a case study and corresponding analysis of the evaluation results were presented, providing detailed insights into the practical application of the proposed framework. The limitations of current research and future research approaches were also discussed. The results indicate that the designed strategy performs well in terms of accuracy and computational convenience, and has potential application prospects

Objective To investigate inequalities in antenatal care initiation and to assess whether early pregnancy recognition may reduce these inequalities. Design Population-based birth cohort study. Setting Rotterdam, the Netherlands. Population A cohort of N=4196 pregnant women from Generation R. Methods The association of individual and socioeconomic factors and gestational age at pregnancy recognition with timing of antenatal care initiation were assessed using linear regression analyses. G-methods were used to estimate the reduction of the inequalities in antenatal care initiation, if everyone would have recognized the pregnancy within 6 weeks after the first day of menstrual period. Main Outcome Measures Antenatal care initiation was derived from electronic patient files of 10 midwifery practices in Rotterdam. Results Those who recognized their pregnancy within 6 weeks (81.7%) had their first antenatal care visit 1.26 weeks (95%CI:-1.59; -0.93) earlier than those who recognized their pregnancy after 6 weeks. All factors were significantly associated with timing of antenatal care initiation. Modeling a situation in which people would recognize their pregnancy within 6 weeks resulted in a significant reduction in the inequalities in antenatal care initiation for age, migration background, pregnancy intention, education, employment, household income, housing, and neighborhood deprivation. Conclusions Early recognition of pregnancy would reduce the impact of socio-economic inequalities in timely initiation of prenatal care.

A case report of drug-Induced hemorrhagic bullae

Although efforts to estimate Ne, Nc, and their ratio in wild populations are expanding, few empirical studies investigate interannual changes in these parameters. Hence, we do not know how representative many estimates may be. Answering this question requires studies of long-term population dynamics. We non-lethally sampled N=5400 brook trout (Salvelinus fontinalis) from seven populations during 6 consecutive years (2014-2019) and genotyped them at 33 microsatellites to examine variation in Ne, Nc and their ratio. Nc was estimated by Mark-Recapture (Nc(MR)) (2014-2018) as well as by Close-Kin-Mark-Recapture (Nc(CKMR)) (2015-2017). Within populations, annual variation in Ne (max/min Ne) ranged from 1.6-fold to 58-fold. Over all 7 populations, median annual variation in Ne was 5-fold. These results reflect important interannual changes in reproductive success variance. Within population Nc(MR) varied by a median of 2.7. Thus, Ne varied nearly twice as much as did Nc(MR) . Our results suggest that, at least in small populations, any single annual estimate of Ne is unlikely to be representative of long-term dynamics. At least 3-4 annual estimates may be required for an estimate of contemporary Ne to be representative. For five of the seven populations, Nc(MR) was indistinguishable from Nc(CKMR). The two populations with discordant estimates exhibited the largest annual Ne variation (58-fold and 35.4-fold). These results suggest sampling effort in these two streams may have been insufficient to capture the genetic diversity of the entire population. Our study demonstrates how knowledge of temporal variation in Ne can be used to identify potential biases in Nc(CKMR).

Colorectal cancer is one of the most prevalent malignancies worldwide， with a tendency of increasing incidence in developed countries, which poses a significant threats to the patients’ physical and mental health. The development of colorectal cancer involves numerous genetic alterations, which indicate that transcription factors may play an important role in this process. Changes in the level of zinc finger proteins, the most prevalent transcription factor, may play an important trigger for the development of colorectal cancer. Different zinc finger proteins play different roles in terms of promoting or inhibiting cancer development. This paper briefly reviews the classification, functional characteristics, and expression changes of zinc finger proteins in colorectal cancer, it focuses on how they regulate gene transcription, influence on common signaling pathways and their potential for translational studies and clinical applications. The objective is to stimulate new ideas for their study in colorectal cancer while also providing foundational information to guide drug development and treatment strategies for colorectal cancer patients in clinical settings.