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Michael Weekes

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

Guangming Wang

and 4 more

Tam Hunt

and 1 more

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

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

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

Mark Ferris

and 14 more

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

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In conventional thermal combustion fuel and air in inflammable proportions are contacted with an ignition source to ignite the mixture which will then continue to burn. Flammable mixtures of most fuels are normally burned at relatively high temperatures, which inherently results in the formation of substantial emissions of nitrogen oxides. In purely catalytic combustion systems, there is little or no nitrogen oxides formed in a system which burns the fuel at relatively low temperatures. The present study is focused primarily upon the combustion characteristics of small alkanes on noble metal surfaces in pre-mixed homogeneous-heterogeneous hybrid systems. The homogeneous-heterogeneous combustion characteristics small alkanes on noble metal surfaces are investigated to gain a greater understanding of the mechanisms of flame stabilization and to gain new insights into how to design pre-mixed combustors with improved stability and robustness. The essential factors for design considerations are determined with improved combustion characteristics. The primary mechanisms responsible for the loss of flame stability are discussed. The present study aims to explore how to effectively operate catalytically stabilized combustion. Particular emphasis is placed upon the catalytic combustion characteristics of small alkanes in the pre-mixed hybrid systems. The results indicate that the combustion effluent is characterized by high thermal energy and typically by low nitrogen oxides content. Precise tuning of the combustion process is needed to establish a balance between stable combustion and low emissions. Simply changing the combustor geometry to maintain near-stoichiometric ratios will not avoid nitrogen oxides formation. The catalytic reactor oxidizes substantially all of the ingested fuel and produces thermal energy. Adiabatic combustion systems, from a practical standpoint, have relatively low heat losses, thus substantially all of the heat released from the combustion zone of such systems appears in the effluent gases as thermal energy for producing power. Catalytic oxidation has the disadvantage that the physical reaction surface which must be supplied for complete oxidation of the fuel increases exponentially with decreasing inlet temperatures, which greatly increases the cost of the combustor and complicates the overall design. The operating temperature is determined by the theoretical adiabatic flame temperature of the fuel-air admixture passed to the combustor and thus is dependent on the initial temperature of the air as well as the amount of fuel contained therein. The temperature of the catalyst zone is controlled by adjusting the composition and initial temperature of the fuel-air admixture as well as the uniformity of the mixture.Keywords: Combustion; Metals; Designs; Fuels; Alkanes; Oxidation

Thomas Johnson

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X-ray computed tomography was applied in imaging 3D printed gyroids used for bioseparation in order to visualize and characterize structures from the entire geometry down to individual nanopores. Methacrylate prints were fabricated with feature sizes of 500 µm, 300 µm and 200 µm, with the material phase exhibiting a porous substructure in all cases. Two X-ray scanners achieved pixel sizes from 5 µm to 16 nm to produce digital representations of samples across multiple length scales as the basis for geometric analysis and flow simulation. At the gyroid scale, imaged samples were visually compared to the original computed aided designs to analyze printing fidelity across all feature sizes. An individual 500 µm feature, part of the overall gyroid structure, was compared and overlaid between the design and imaged volumes where individual printed layers could be identified. Internal subvolumes of all feature sizes were segmented into material and void phases for permeable flow analysis. Small pieces of 3D printed material were optimized for nanotomographic imaging at a pixel size of 63 nm, with all three gyroid samples exhibiting similar geometric characteristics when measured. An average porosity of 45% was obtained that was within the expected design range and a tortuosity factor of 2.52 was measured. Applying a voidage network map enabled the size, location and connectivity of individual pores to be identified, obtaining an average internal pore size of 793 nm. Using the Avizo XLAB plugin at a bulk diffusivity of 7.00 x10 -11 m 2s -1 resulted in a simulated material diffusivity of 2.17 x10 -11 m 2s -1 ± 0.16 x10 -11 m 2s -1.

Xi Jin

and 5 more

Bernt Nilsson

and 7 more

The methodology for production of biologics is going through a paradigm shift from batch-wise operation to continuous production. Lot of efforts are focused on integration, intensification and continuous operation for decreased foot-print, material, equipment and increased productivity and product quality. These integrated continuous processes with on-line analytics becomes complex processes, which requires automation, monitoring and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allow fast development, advanced studies and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible and extendable real-time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real-time execution. Integrated continuous processing often imply parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model-based and plant-wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring and model-based batch-to-batch control.

Baidehi Mitra

and 1 more

Cancer is the primary cause of death worldwide, accounting for almost 10 million deaths. The most prevalent are lung, breast, colorectal, and skin cancer. Cancer does not obey the cell cycle which can lead to the formation of tumors. The biogenic amine histamine is synthesized by histidine. Increased amounts of histamine have been linked to the regulation of several tumors. The histamine receptors (H1, H2, H3, and H4) are distributed throughout the skin, where H1 and H2 are the primary targets for drug therapy. Repurposing of the current antihistamine drugs can be cost-effective, safe medications and allied with lesser adverse effects. Researchers examined Six H1-antihistamines (Cetirizine, clemastine, desloratadine, loratadine, ebastine, and fexofenadine) in a nationwide wide cohort study of all Swedish patients with ten types of immunogenic (melanoma, bladder cancer, kidney, prostate, lung, pancreatic, colorectal, breast cancer, and Hodgkin lymphoma) and six non-immunogenic (thyroid cancer, liver, ovarian, brain cancer and lymphoma) tumors. The study shows that Desloratadine and loratadine upsurge the survival rate for many tumors by inhibiting the growth of tumors and promoting apoptotic cell death. The other H1 receptor antagonist Cloperastine knockdown FGF13 expression which is responsible for anticancer agent cisplatin-resistance and selectively kills HeLa cisR cells. Some findings believe H1 receptor antagonists should be investigated in randomized clinical trials for immunogenic tumors. These drugs can be a curative therapy for several tumors including that prognosis with limited treatment options.

Riccardo Ton

and 4 more

Heat waves are predicted to be detrimental for organismal physiology with costs for survival that could be reflected in markers of biological state such as telomeres. Changes in early life telomere dynamics driven by thermal stress are of particular interest during the early post-natal stages of altricial birds because nestlings quickly shift from being ectothermic to poikilothermic to endothermic after hatching. Telomeres of ectothermic and endothermic organisms respond differently to environmental temperature, but investigations within species that transition from ectothermy to endothermy are lacking. Also, ambient temperature influences parental brooding behavior, which will alter the temperature experienced by offspring and thereby, potentially, their telomeres. We exposed zebra finch nestlings to experimental heat waves, and compared their telomere dynamics to that of a control group at 5, 12 and 80 days of age that correspond to three different thermoregulatory stages (ectothermic, poikilothermic and endothermic respectively); we also recorded parental brooding, offspring sex, mass, growth rates, brood size and hatch order. Nestling mass showed an inverse relationship with telomere length, and nestlings exposed to heat waves showed lower telomere attrition during their first 12 days of life (poikilothermic stage) compared to controls. Additionally, parents of heated broods reduced the time they spent brooding offspring (at five days old) compared to controls. Lower brooding effort was associated with shorter telomeres in 12 day old nestlings. Our results indicate that the effect of heat waves on telomere dynamics likely varies depending on age and thermoregulatory stage of the offspring in combination with parental brooding behavior during growth.

Toni Jernfors

and 9 more

Dibyendu Biswas

and 1 more

Vultures are a specialized species group, utilizing wide habitat and forage niches and their long-term survival depends on the protection of their critical habitats. Taking a landscape approach, we modelled the distribution of nest sites (n = 30) and roost sites (n = 31) of cliff-nesting vultures (four species) in the Greater Panna Landscape (GPL), central India. We performed Random Forest (RF), Generalized Linear Model (GLM) and Boosted Regression Tree (BRT) algorithms. The AUC values for the predictive distribution of nests were 0.97, 0.90, 0.97 for RF, GLM and BRT, respectively, while for roost distribution it was found to be 0.76, 0.63, 0.74 for RF, GLM and BRT, respectively. We ensembled the predictions of all three methods for better accuracy and combined the model outputs. We then performed zonation analysis on the final map and used Human footprint as a proxy for conservation cost to define spatial prioritization for conservation inputs. The results reveal that the GPL has a total of 9,402 sq. km. area within the top 20 ranks in terms of conservation prioritization for nesting and roosting. Given the cost value, the top 20 ranked units will account for approximately 60% of the critical habitats and these may be the focus of long-term conservation inputs to sustain the vulture populations in the landscape. The spatially explicit outputs based on the robust methodology involving intensive fieldwork and ensembled modelling offer a basis for local scale and landscape scale actions, which can be replicated in other parts of the vulture distribution ranges.

Chunfu Zheng

and 9 more

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Selim Polat

and 3 more

Objective: The aim of this research was to elucidate the effect of deep brain stimulation on apathy, and cognitive functions in the pre and post-operative period. Materials & Methods: This study was conducted in Adana City Training & Research Hospital, Parkinson and Movement Disorders Center between January to December 2022. Individuals were evaluated by a multidisciplinary commission consisting of neurology, neurosurgery and psychiatrists. Thirty six, aged between 18–70 years who underwent Deep Brain Stimulation at the neurosurgery clinic were included in the study. Hamiltonanxiety and depression, apathy assessment, standard mini-mental test and Montreal Cognitive Assessment scales are applied to the patients. Results: The mean Apathy Score at the pre-op was 47.77±15.83 in patients who had undergone DBS operation while it was 30.83±13.59 in the post–op. This decrease was statistically significant (p<0.003) and indicated clinical improvement. The average Hamilton Anxiety scale scores at the pre–op was 11.50±5.14, and s 10.22±5.57 at the post-op with no clinical significance (p=0.28). The UPDRS-ON value was determined as 22.55±7.53 in the pre–op and 14.50±6.99 in the post–op significantly (p<0.001). UPDRS-OFF was found to be significant with pre–op 37.44±9.85, compared to post–op 23.44±7.86 (p<0.001). Conclusion: Regarding the results of this study, it was found that sub – thalamic stimulation led to stabilization of both motor and non-motor complications. Additionally DBS ameliorated apathy and Parkinson’s Disease symptoms of patients significantly. Future studies with larger sample size that focus on both pharmacological and non-pharmacological treatments might provide better clinical aspects.

Yuyun Yang

and 1 more

It is widely recognized that fluid injection can trigger fault slip. However, the processes by which the fluid-rock interactions facilitate or inhibit slip are poorly understood and some are neglected or oversimplified in most models of injection-induced slip. In this study, we perform a 2D antiplane shear investigation of aseismic slip that occurs in response to fluid injection into a permeable fault governed by rate-and-state friction. We account for pore dilatancy and permeability changes that accompany slip, and quantify how these processes affect pore pressure diffusion, which couples to aseismic slip. The fault response to injection has two phases. In the first phase, slip is negligible and pore pressure closely follows the standard linear diffusion model. Pressurization of the fault eventually triggers aseismic slip in the immediate vicinity of the injection site. In the second phase, the aseismic slip front expands outward and dilatancy causes pore pressure to depart from the linear diffusion model. Aseismic slip front overtakes pore pressure contours, with both subsequently advancing at constant rate along fault. We quantify how prestress, initial state variable, injection rate, and frictional properties affect the migration rate of the aseismic slip front, finding values ranging from less than 50 to 1000 m/day for typical parameters. Additionally, we compare to the case when porosity and permeability evolution are neglected. In this case, the aseismic slip front migration rate and total slip are much higher. Our modeling demonstrates that porosity and permeability evolution, especially dilatancy, fundamentally alters how faults respond to fluid injection.

Menaka Revel

and 3 more

Understanding spatial and temporal variations in terrestrial waters is key to assessing the global hydrological cycle. The future Surface Water and Ocean Topography (SWOT) satellite mission will observe the elevation and slope of surface waters at <100 m resolution. Methods for incorporating SWOT measurements into river hydrodynamic models have been developed to generate spatially and temporally continuous discharge estimates. However, most of SWOT data assimilation studies have been performed on a local scale. We developed a novel framework for estimating river discharge on a global scale by incorporating SWOT observations into the CaMa-Flood hydrodynamic model. The local ensemble transform Kalman filter with adaptive local patches was used to assimilate SWOT observations. We tested the framework using multi-model runoff forcing and/or inaccurate model parameters represented by corrupted Manning’s coefficient. Assimilation of virtual SWOT observations considerably improved river discharge estimates for continental-scale rivers at high latitudes (>50°) and also downstream river reaches at low latitudes. High assimilation efficiency in downstream river reaches was due to both local state correction and the propagation of corrected hydrodynamic states from upstream river reaches. Accurate global river discharge estimates were obtained (Kling–Gupta efficiency [KGE] > 0.90) in river reaches with > 270 accumulated overpasses per SWOT cycle when no model error was assumed. Introducing model errors decreased this accuracy (KGE ≈ 0.85). Therefore, improved hydrodynamic models are essential for maximizing SWOT information. These synthetic experiments showed where discharge estimates can be improved using SWOT observations. Further advances are needed for data assimilation on global-scale.

Ge Li

and 1 more

The Leech River fault (LRF) zone located on southern Vancouver Island is a major regional seismic source. We investigate potential interactions between earthquake ruptures on the LRF and the neighboring Southern Whidbey Island fault (SWIF), which can be interpreted as a step-over fault system. Using a linear slip-weakening frictional law, we perform 3D finite element simulations to study rupture jumping scenarios from the LRF (source fault) to the SWIF (receiver fault), focusing on the influences of the offset distance, fault initial stress level, and fault burial depth. We find a smaller offset distance, a higher initial stress level on either fault or a shallower fault burial depth will promote rupture jumping. Jumping scenarios can be interpreted as the response of the receiver fault to stress perturbations radiated from the source fault rupture. We demonstrate that the final rupture jumping scenario depends on various parameters, which can be collectively quantified by two keystone variables, the time-averaged Over Stressed Zone (where shear stress exceeds static frictional strength on the receiver fault) size $\overline{R_e}$ and the receiver fault initial stress level. Specifically, a smaller offset distance, a higher initial shear stress level, or a shallower burial depth will lead to a larger $\overline{R_e}$. The seismic moment on the receiver fault increases with increasing $\overline{R_e}$. When $\overline{R_e}$ reaches the threshold dependent on the receiver fault initial stress level, the rupture becomes break-away.
This study presents the micro- and macrophysical cloud properties as a function of their surface coupling state with the sea ice during the wintertime of the MOSAiC field experiment. Cloud properties such as cloud base height, liquid- and ice water content have been previously found to have statistically distinguished features under the presence of sea ice leads (characterized by sea ice concentration, SIC) along downwind direction from the central observatory RV  Polarstern. Those findings are mainly in an increase of liquid water content, and favored occurrence of low level clouds as contrasted to situations when the clouds are thermodynamically decoupled.The present contribution is an update considering two recent developments in the liquid detection in clouds and in the detection of sea ice leads. First, radar and lidar-based cloud droplet detection approaches like Cloudnet (Illingworth et al. 2007, Tukiainen et al. 2020) using Arctic wintertime observations and applied to measurements by the Atmospheric Radiation Measurement mobile facility (ARM) instrumental suite on-board the RV Polarstern during  MOSAiC.Secondly, we explore a new sea ice lead fraction product based on sea ice divergence. Sea ice divergence is estimated from sequential images of space-borne synthetic aperture radar with a spatial resolution of 700 m. The lead divergence product, being independent of cloud coverage, offers the unique advantage to detect opening leads at high spatial resolution.Statistics for the wintertime cloud properties based on the coupling state with the sea ice concentration and sea ice lead fraction will be presented as an approach to study Arctic clouds and their interaction with sea ice.

Margaret L Duffy

and 1 more

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

Monique Weemstra

and 3 more

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

Bryce E Harrop

and 12 more

The water cycle is an important component of the earth system and it plays a key role in many facets of society, including energy production, agriculture, and human health and safety. In this study, the Energy Exascale Earth System Model version 1 (E3SMv1) is run with low-resolution (roughly 110 km) and high-resolution (roughly 25 km) configurations — as established by the High Resolution Model Intercomparison Project protocol — to evaluate the atmospheric and terrestrial water budgets over the conterminous United States (CONUS) at the large watershed scale. The water cycle slows down in the HR experiment relative to the LR, with decreasing fluxes of precipitation, evapotranspiration, atmospheric moisture convergence, and runoff. The reductions in these terms exacerbate biases for some watersheds, while reducing them in others. For example, precipitation biases are exacerbated at HR over the Eastern and Central CONUS watersheds, while precipitation biases are reduced at HR over the Western CONUS watersheds. The most pronounced changes to the water cycle come from reductions in precipitation and evapotranspiration, the latter of which results from decreases in evaporative fraction. While the HR simulation is warmer than the LR, moisture convergence decreases despite the increased atmospheric water vapor, suggesting circulation biases are an important factor. Additional exploratory metrics show improvements to water cycle extremes (both in precipitation and streamflow), fractional contributions of different storm types to total precipitation, and mountain snowpack.

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