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Background: Social care integration refers to the incorporation of activities into health systems that assist patients with health-related social needs (HRSNs) that negatively impact the health outcomes of their patients, such as food insecurity or homelessness. Social care integration initiatives are becoming more common. The COVID-19 pandemic strained health systems while simultaneously increasing levels of unmet social needs. Objective: To describe the effects of the COVID-19 pandemic on established social care delivery in a primary care setting. Design: We used qualitative semi-structured interviews of stakeholders to assess barriers and facilitators to social care delivery in the primary care setting during the COVID-19 health emergency. Data was analyzed using a hybrid inductive/deductive thematic analysis approach with both the Consolidated Framework for Implementation Research (CFIR) and the Screen-Navigate-Connect-Address-Evaluate model of social care integration. Setting: Two safety-net, hospital-based primary care clinics with established screening for food insecurity, homelessness, and legal needs. Participants: Six physicians, six nurses, six members of the social work team (clinical social workers and medical case workers), six community health workers, and six patients (total N = 30) completed interviews. Results: Four major themes were identified. (1) A strained workforce experienced challenges confronting increased levels of HRSNs. (2) Vulnerable populations experienced a disproportionate negative impact in coping with effects of the COVID-19 pandemic on HRSNs. (3) COVID-19 protections compounded social isolation but did not extinguish the sense of community. (4) Fluctuations in the social service landscape led to variable experiences. Conclusions: The COVID-19 pandemic disrupted established social care delivery in a primary care setting. Many of the lessons learned about challenges to social care delivery when health systems are strained are important considerations that can inform efforts to expand social care delivery. [ABSTRACT FROM AUTHOR]

The aquaculture industry is increasingly pursuing sustainable and effective alternatives to traditional fishmeal and fish oil-based feeds due to their economic and ecological drawbacks. Red yeast (Sporidiobolus pararoseus) has demonstrated potential as a functional feed additive due to its bioactive compounds, which can boost growth and immunity in fish. Here, this study investigated the effects of varying concentrations of red yeast (RY) in the diet of koi carp (Cyprinus carpio var. koi) cultured in biofloc systems. Three hundred fish (27.62 ± 0.08 g) was randomly distributed into 15 fiberglass tanks (150 L each) across five dietary treatments: 0 g/kg (control), 5 g/kg (RY-1), 10 g/kg (RY-2), 20 g/kg (RY-3), and 40 g/kg (RY-4). Each treatment was replicated 3 times, and the experiment lasted for 8 weeks. After 8 weeks of feeding trial, fish fed the 40 g/kg RY diet showed significantly higher weight gain (WG), specific growth rates (SGR), and final weight (FW). Additionally, the feed conversion ratio (FCR) was significantly lower in the 40 g/kg RY diet group (p < 0.05). There was a strong positive correlation between RY concentration levels and WG, FW, and SGR (r = 0.695, 0.699, and 0.694, respectively), while a negative correlation was observed for FCR (r =—0.505). No significant differences were observed in survival rate (SR) between the RY-supplemented groups and the control group (p > 0.05). However, skin mucus and serum lysozyme activities increased significantly in fish fed the 40 g/kg RY diet (p < 0.05), while peroxidase activity remained unchanged compared to the control group (p > 0.05). Additionally, mRNA transcript levels of both pro-inflammatory (il-1β, il-8, and tnf-α) (approx. 1.76- to 1.87-fold) and anti-inflammatory (il-10 and tgf-β) (approx. 1.35- to 2.86-fold) cytokines in the spleen and intestine were upregulated with higher dietary RY levels compared to the control group (0 g/kg). These findings suggest that dietary inclusion of RY at 40 g/kg could be beneficial as a functional feed additive for koi carp. [ABSTRACT FROM AUTHOR]

Deep borehole heat exchangers (DBHEs) with depths exceeding 500 m have been researched comprehensively in the literature, focusing on both applications and subsurface modelling. This review focuses on conventional (vertical) DBHEs and provides a critical literature survey to analyse (i) methodologies for modelling; (ii) results from heat extraction modelling; (iii) results from modelling deep borehole thermal energy storage; (iv) results from heating and cooling models; and (v) real case studies. Numerical models generally compare well to analytical models whilst maintaining more flexibility, but often with increased computational resources. Whilst in-situ geological parameters cannot be readily modified without resorting to well stimulation techniques (e.g. hydraulic or chemical stimulation), engineering system parameters (such as mass flow rate of the heat transfer fluid) can be optimised to increase thermal yield and overall system performance, and minimise pressure drops. In this active research area, gaps remain, such as limited detailed studies into the effects of geological heterogeneity on heat extraction. Other less studied areas include: DBHE arrays, boundary conditions and modes of operation. A small number of studies have been conducted to investigate the potential for deep borehole thermal energy storage (BTES) and an overview of storage efficiency metrics is provided herein to bring consistency to the reporting of thermal energy storage performance of such systems. The modifications required to accommodate cooling loads are also presented. Finally, the active field of DBHE research is generating a growing number of case studies, particularly in areas with low-cost drilling supply chains or abandoned hydrocarbon or geothermal wells suitable for repurposing. Existing and planned projects are thus presented for conventional (vertical) DBHEs. Despite growing interest in this area of research, further work is needed to explore DBHE systems for cooling and thermal energy storage. [ABSTRACT FROM AUTHOR]

Supramolecular polymer networks contain non-covalent cross-links that enable access to broadly tunable mechanical properties and stimuli-responsive behaviors; the incorporation of multiple unique non-covalent cross-links within such materials further expands their mechanical responses and functionality. To date, however, the design of such materials has been accomplished through discrete combinations of distinct interaction types in series, limiting materials design logic. Here we introduce the concept of leveraging "nested" supramolecular crosslinks, wherein two distinct types of non-covalent interactions exist in parallel, to control bulk material functions. To demonstrate this concept, we use polymer-linked Pd2L4 metal–organic cage (polyMOC) gels that form hollow metal–organic cage junctions through metal–ligand coordination and can exhibit well-defined host-guest binding within their cavity. In these "nested" supramolecular network junctions, the thermodynamics of host-guest interactions within the junctions affect the metal–ligand interactions that form those junctions, ultimately translating to substantial guest-dependent changes in bulk material properties that could not be achieved in traditional supramolecular networks with multiple interactions in series. Supramolecular polymer networks have unique and useful properties due to the reversible nature of their cross-links. Here, the authors show that when two distinct supramolecular interaction classes exist within a single cross-link, new functions can result. [ABSTRACT FROM AUTHOR]

Objectives: To compare predictive significance of sarcopenia and clinical frailty scale (CFS) in terms of postoperative mortality in patients undergoing emergency laparotomy Methods: In compliance with STROCSS statement standards, a retrospective cohort study with prospective data collection approach was conducted. The study period was between January 2017 and January 2022. All adult patients with non-traumatic acute abdominal pathology who underwent emergency laparotomy in our centre were included. The primary outcome was 30-day mortality and secondary outcomes were in-hospital mortality and 90-day mortality. The predictive value of sarcopenia and CFS were compared using the receiver operating characteristic (ROC) curve analysis and multivariable binary logistic regression analysis. Results: A total of 1043 eligible patients were included. The risk of 30-day mortality, in-hospital mortality, and 90-day mortality were 8%, 10%, and 11%, respectively. ROC curve analysis suggested that sarcopenia is a significantly stronger predictor of 30-day mortality (AUC: 0.87 vs. 0.70, P<0.0001), in-hospital mortality (AUC: 0.79 vs. 0.67, P=0.0011), and 90-day mortality (AUC: 0.79 vs. 0.67, P=0.0009) compared with CFS. Moreover, multivariable binary logistic regression analysis identified sarcopenia as an independent predictor of mortality [coefficient: 4.333, OR: 76.16 (95% CI 37.06–156.52), P<0.0001] but not the CFS [coefficient: 0.096, OR: 1.10 (95% CI 0.88–1.38), P=0.4047]. Conclusions: Sarcopenia is a stronger predictor of postoperative mortality compared with CFS in patients undergoing emergency laparotomy. It cancels out the predictive value of clinical frailty scale in multivariable analyses; hence among the two variables, sarcopenia deserves to be included in preoperative predictive tools. [ABSTRACT FROM AUTHOR]

This paper responds to an argument from Botin which claims that Russellian physicalism is committed to the view that either (i) our phenomenal concepts do not reveal anything essential about phenomenal properties (following Goff, Botin calls this the 'opaque' account of phenomenal concepts), or that (ii) phenomenal concepts are capable of revealing at least some of the essence of phenomenal properties—making phenomenal concepts 'translucent' if some-but-not-all-revealing or 'transparent' if all-revealing—but this entails that phenomenal properties are fundamental, which violates physicalism. I argue that Botin is wrong that Russellian physicalists are committed to the view that physical and phenomenal concepts must have similarly qualitative/phenomenal modes of presentation or contents, since Russellian physicalists assume that we do not possess concepts which specifically refer to non-phenomenal categorical properties. If we were to acquire concepts for non-phenomenal categorical properties, they would need to have categorical contents and modes of presentation, but need not have qualitative/phenomenal contents and modes of presentation. Given this, Russellian physicalists can embrace a translucent account of phenomenal concepts, and hold that our phenomenal concepts more-or-less accurately tell us about certain sorts of non-fundamental properties which are both physical and categorical. [ABSTRACT FROM AUTHOR]

The structure, stability, and intermolecular rearrangements between ortho-, meta-, and para-C2B10H12, and B12H2−12 were investigated using the hybrid density functional B3LYP/6-31G(d) for vibrational frequencies, as well as B3LYP/6-311+G(2d,p) for single-point electronic energies. The general trends in free energies of rearrangement between ortho-C2B10H12 to meta-C2B10H12 and meta-C2B10H12 to para-C2B10H12 presented here are consistent with experimental reaction temperatures. In addition, the majority of the rearrangements can be viewed in terms of concerted diamond–square–diamond steps and triangular-face-rotations. [ABSTRACT FROM AUTHOR]

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10−8, we confirmed association of the FADS signal and found evidence of two additional signals (in DAGLA and BEST1) within 200 kb of the originally reported FADS signal. Outside of the FADS region, we identified novel signals for arachidonic acid (AA) in Hispanic Americans located in/near genes including TMX2, SLC29A2, ANKRD13D and POLD4, and spanning a > 9 Mb region on chromosome 11 (57.5 Mb ~ 67.1 Mb). Among these novel signals, we found associations unique to Hispanic Americans, including rs28364240, a POLD4 missense variant for AA that is common in CHARGE Hispanic Americans but absent in other race/ancestry groups. Our study sheds light on the genetics of PUFAs and the value of investigating complex trait genetics across diverse ancestry populations. A genome-wide association study highlights the shared or unique genetic etiology of polyunsaturated fatty acids across diverse ancestry groups. [ABSTRACT FROM AUTHOR]

Russellian physicalism is a promising answer to the mind–body problem which attempts to satisfy the motivating epistemic and metaphysical concerns of non-physicalists with regards to consciousness, while also maintaining a physicalist commitment to the non-existence of fundamental mentality. Chan (Philosophical Studies, 178:2043–62, 2021) has recently described a challenge to Russellian physicalism he deems the 'difference-maker problem', which is a Russellian-physicalism-specific version of the more well-known 'combination problem' for Russellian monism generally. The problem is to determine how a relatively small set of fundamental categorical property types can ground the large variety of phenomenal properties that exist. To answer this problem, a Russellian physicalist can say that there is strong emergence from fundamental categorical properties to phenomenal properties, or she can say that there is only weak emergence from fundamental categorical properties to phenomenal properties. Chan argues that neither of these routes are viable for Russellian physicalism. This paper constitutes a response to Chan, arguing that Russellian physicalists can embrace either weak or strong emergence to explain phenomenal variety. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies. Here the authors propose an RNA interference-based switch for dynamic control of AAV transgene expression. In this approach, transgene expression may be silenced by RNAi and subsequently recovered using REVERSIR oligonucleotides. [ABSTRACT FROM AUTHOR]

Policymakers' demands for improved academic achievement by all children and the standardization of instructional practices continue to alter the landscape of early childhood education. Many within the early childhood education community are examining how these changes impact stakeholders' conceptions of school readiness. Yet, little has been done to examine how these same stakeholders make sense of the changed practices of kindergarten itself—the program for which children are getting ready. This article addresses this issue by examining findings from an instrumental case study that examined how a sample of urban prekindergarten program stakeholders in the Midwest made sense of the changed kindergarten. Investigating this issue created the opportunity to consider whether preschool stakeholders are conceptually prepared for children transitioning into kindergarten, which may impact how children's transition into elementary school unfolds, as well as whether they believe the changed kindergarten is an appropriate learning environment for children. Such findings also offer the chance to consider how early childhood stakeholders might work to alter the current framing of the changed kindergarten. [ABSTRACT FROM AUTHOR]

Discrimination of pain intensity using machine learning (ML) and electroencephalography (EEG) has significant potential for clinical applications, especially in scenarios where self-report is unsuitable. However, existing research is limited due to a lack of external validation (assessing performance using novel data). We aimed for the first external validation study for pain intensity classification with EEG. Pneumatic pressure stimuli were delivered to the fingernail bed at high and low pain intensities during two independent EEG experiments with healthy participants. Study one (n = 25) was utilised for training and cross-validation. Study two (n = 15) was used for external validation one (identical stimulation parameters to study one) and external validation two (new stimulation parameters). Time–frequency features of peri-stimulus EEG were computed on a single-trial basis for all electrodes. ML training and analysis were performed on a subset of features, identified through feature selection, which were distributed across scalp electrodes and included frontal, central, and parietal regions. Results demonstrated that ML models outperformed chance. The Random Forest (RF) achieved the greatest accuracies of 73.18, 68.32 and 60.42% for cross-validation, external validation one and two, respectively. Importantly, this research is the first to externally validate ML and EEG for the classification of intensity during experimental pain, demonstrating promising performance which generalises to novel samples and paradigms. These findings offer the most rigorous estimates of ML's clinical potential for pain classification. [ABSTRACT FROM AUTHOR]

Microbial symbionts enable many phytophagous insects to specialize on plant-based diets through a range of metabolic services. Pollen comprises one-plant tissue consumed by such herbivores. While rich in lipids and proteins, its nutrient content is often imbalanced and difficult-to-access due to a digestibly recalcitrant cell wall. Pollen quality can be further degraded by harmful allelochemicals. To identify microbes that may aid in palynivory, we performed cDNA-based 16S rRNA metabarcoding on three related pollen beetles (Nitidulidae: Meligethinae) exhibiting different dietary breadths: Brassicogethes aeneus, B. matronalis, and Meligethes atratus. Nine bacterial symbionts (i.e., 97% OTUs) exhibited high metabolic activity during active feeding. Subsequent PCR surveys revealed varying prevalence of those from three Rickettsialles genera—Lariskella, Rickettsia, and Wolbachia—within beetle populations. Our findings lay the groundwork for future studies on the influence of phylogeny and diet on palynivorous insect microbiomes, and roles of symbionts in the use of challenging diets. [ABSTRACT FROM AUTHOR]

Though there is yet no consensus on the right way to understand ‘physicalism’, most philosophers agree that, regardless of whatever else is required, physicalism cannot be true if there exists fundamental mentality. I will follow Jessica Wilson (Philosophical Studies 131:61–99, 2006) in calling this the 'No Fundamental Mentality' (NFM) constraint on physicalism. Unfortunately for those who wish to constrain physicalism in this way, NFM admits of a counterexample: an artificially intelligent quantum computer which employs quantum properties as part of its cognitive operations. If one of these quantum properties serves a proper functional role in the artificial intelligence, then that property counts as a mental under the physicalism-friendly theory of mentality called “realizer functionalism”, which says that a lower-order property is mental if it satisfies an appropriate higher-order functional description. Further, if this quantum property is both fundamental and mental, then NFM must rule that it is not physical. Yet the existence of such an artificially intelligent quantum computer, which possesses mental properties solely in virtue of the functional roles those properties play, is surely consistent with the truth of physicalism. This ought to motivate NFM proponents to reformulate their view. [ABSTRACT FROM AUTHOR]

Russellian physicalism is a view on the nature of consciousness which promises to satisfy the demands of both traditional physicalists and non-physicalists. It does so by identifying subjective experience with physically acceptable categorical properties underlying structural and dispositional properties described by science. Though promising, the view faces at least two serious challenges: (i) it has been argued that science deals in both categorical and non-categorical properties, which would undercut the motivation behind Russellian physicalism, and (ii) it has been argued that only nonphysicalist Russellian views—like panpsychism—are useful when it comes to explaining consciousness. I address these criticisms, arguing that there is no viable reason for maintaining that science deals in categorical properties of the sort which a Russellian physicalist is interested in, and that features of fully-physical categorical properties can be described which provide useful explanations for various essential features of subjective experience. These projects are connected: it turns out that when the explanatory relevance of Russellian physicalism is explained in detail, constraints are put the sort of categorical properties that Russellian physicalists can say are left out of science. Specifically, Russellian physicalists are forced to subscribe to the view that science leaves out any categorical properties whatsoever, as opposed to the view that some scientifically scrutable properties are categorical, but not the ones which Russellian physicalists are interested in. I hope that by addressing these criticisms of Russellian physicalism, and drawing logical connections between the responses, further appeal is added to a promising, but so far relatively unexplored, view. [ABSTRACT FROM AUTHOR]

We introduce an experimental version of GeoGebra that successfully conjectures and proves a large scale of geometric inequalities by providing an easy-to-use graphical interface. GeoGebra Discovery includes an embedded version of the Tarski/QEPCAD B system which can solve a real quantifier elimination problem, so the input geometric construction can be translated into a semi-algebraic system, and after some algebraic manipulations, the obtained formula can be translated back to a precisely stated geometric inequality. We provide some non-trivial examples to illustrate the performance of GeoGebra Discovery when dealing with inequalities, as well as some technical difficulties. [ABSTRACT FROM AUTHOR]

Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional organs. Here we show that conjugation of 2′-O-hexadecyl (C16) to siRNAs enables safe, potent and durable silencing in the central nervous system (CNS), eye and lung in rodents and non-human primates with broad cell type specificity. We show that intrathecally or intracerebroventricularly delivered C16-siRNAs were active across CNS regions and cell types, with sustained RNA interference (RNAi) activity for at least 3 months. Similarly, intravitreal administration to the eye or intranasal administration to the lung resulted in a potent and durable knockdown. The preclinical efficacy of an siRNA targeting the amyloid precursor protein was evaluated through intracerebroventricular dosing in a mouse model of Alzheimer's disease, resulting in amelioration of physiological and behavioral deficits. Altogether, C16 conjugation of siRNAs has the potential for safe therapeutic silencing of target genes outside the liver with infrequent dosing. Lipophilic siRNA conjugates exert therapeutic activity in the mouse CNS. [ABSTRACT FROM AUTHOR]

Around 36,000 km3 of freshwater flows through rivers and estuarine ecosystems and enter the world's coastal fishing regions every year. The flow of freshwater and sediments creates regional changes in coastal circulation, stimulates marine productivity and helps define the hydrologic properties of estuarine and oceanic waters. These processes can affect different life stages of marine species either directly, through variations in salinity and temperature, or indirectly, due to changes in the availability of food and habitat. This paper reviews the relationship between freshwater flowing through estuarine and coastal ecosystems, and the variable productivity associated with global marine capture fisheries. The results of a global synthesis revealed that 72% of species representing 77% of the total catch (43 million tonnes) were linked to river flows for at least some part of their life cycle. Insights into how the relationship between flow and fishery production varies globally indicates wild capture fisheries and freshwater resources would benefit from an integrated planning and management approach. [ABSTRACT FROM AUTHOR]

An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications. Approaches have been devised to increase the discovery rate of intrabodies but often these yield results that aren't functional in cells. Here the authors engineer and optimise an autonomous and disulphide-free human VH domain for intracellular expression, and they identify several VH domain binders against eIF4E. [ABSTRACT FROM AUTHOR]

A soft and flexible wearable sweat epidermal microfluidic device capable of simultaneously stimulating, collecting, and electrochemically analyzing sweat is demonstrated. The device represents the first system integrating an iontophoretic pilocarpine delivery system around the inlet channels of epidermal polydimethylsiloxane (PDMS) microfluidic device for sweat collection and analysis. The freshly generated sweat is naturally pumped into the fluidic inlet without the need of exercising. Soft skin-mounted systems, incorporating non-invasive, on-demand sweat sampling/analysis interfaces for tracking target biomarkers, are in urgent need. Existing skin conformal microfluidic-based sensors for continuous monitoring of target sweat biomarkers rely on assays during intense physical exercising. This work demonstrates the first example of combining sweat stimulation, through transdermal pilocarpine delivery, with sample collection through a microfluidic channel for real-time electrochemical monitoring of sweat glucose, in a fully integrated soft and flexible multiplexed device which eliminates the need of exercising. The on-body operational performance and layout of the device were optimized considering the fluid dynamics and evaluated for detecting sweat glucose in several volunteers. Furthermore, the microfluidic monitoring device was integrated with a real-time wireless data transmission system using a flexible electronic board PCB conformal with the body. The new microfluidic platform paves the way to real-time non-invasive monitoring of biomarkers in stimulated sweat samples for diverse healthcare and wellness applications. [ABSTRACT FROM AUTHOR]

Unlike satellite images, which are typically acquired and processed in near-real-time, global land cover products have historically been produced on an annual basis, often with substantial lag times between image processing and dataset release. We developed a new automated approach for globally consistent, high resolution, near real-time (NRT) land use land cover (LULC) classification leveraging deep learning on 10 m Sentinel-2 imagery. We utilize a highly scalable cloud-based system to apply this approach and provide an open, continuous feed of LULC predictions in parallel with Sentinel-2 acquisitions. This first-of-its-kind NRT product, which we collectively refer to as Dynamic World, accommodates a variety of user needs ranging from extremely up-to-date LULC data to custom global composites representing user-specified date ranges. Furthermore, the continuous nature of the product's outputs enables refinement, extension, and even redefinition of the LULC classification. In combination, these unique attributes enable unprecedented flexibility for a diverse community of users across a variety of disciplines. Measurement(s) land use • land cover Technology Type(s) deep learning [ABSTRACT FROM AUTHOR]

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories. [ABSTRACT FROM AUTHOR]

As population growth and urbanization are steadily rising, the need for dependable flood estimation techniques is crucial. This study evaluates extreme flood events in select sub-basins of the Lower St. Johns River in Florida, USA. The study considers the effect of urbanization on the natural hydrologic processes and flood magnitudes in the watershed. Additionally, the effects of varying seasonality into the hydrologic modeling procedure are also investigated. This research focuses on determining the 10-, 25-, 50-, and 100-year return frequency flood flows in Julington Creek, Ortega River, and Pablo Creek of the Lower St. Johns River Basin in Florida, USA. The major findings of this research indicate that by implementing a range of flood estimation methods one can better describe the inherent uncertainty with traditional estimates. Also, the research showed that varying seasonality in the hydrologic modeling procedure does not result in vast differences in the resulting flood estimates. However, various land-use scenarios may produce simulated flood flows of greater magnitude—especially when a more urbanized land-use scenario is modeled. [ABSTRACT FROM AUTHOR]

Regardless of whatever else physicalism requires, nearly all philosophers agree that physicalism cannot be true in a world which contains fundamental mentality. I challenge this widely held attitude, and describe a world which is plausibly all-physical, yet which may contain fundamental mentality. This is a world in which priority monism is true—which is the view that the whole of the cosmos is fundamental, with dependence relations directed from the whole to the parts—and which contains only a single mental system, like a brain or computer. Because some properties of the whole are fundamental under priority monism, it follows that that the mental properties of a cosmos-encompassing brain or computer system may be fundamental in a priority monist world. Yet such a world need not contain anything physically unacceptable: the mental properties of the cosmos-encompassing brain or computer can be characterized in a physicalism-friendly functionalist or identity-theoretic way. Thus, as I see it, physicalism need not be false in such a world. This constitutes a challenge to those who hold the view that physicalism is inconsistent with the existence of fundamental mentality. [ABSTRACT FROM AUTHOR]

Parallel patterns are a high-level programming paradigm that enables non-experts in parallelism to develop structured parallel programs that are maintainable, adaptive, and portable whilst achieving good performance on a variety of parallel systems. However, there still exists a large base of legacy-parallel code developed using ad-hoc methods and incorporating low-level parallel/concurrency libraries such as pthreads without any parallel patterns in the fundamental design. This code would benefit from being restructured and rewritten into pattern-based code. However, the process of rewriting the code is laborious and error-prone, due to typical concurrency and pthreading code being closely intertwined throughout the business logic of the program. In this paper, we present a new software restoration methodology, to transform legacy-parallel programs implemented using pthreads into structured farm and pipeline patterned equivalents. We demonstrate our restoration technique on a number of benchmarks, allowing the introduction of patterned farm and pipeline parallelism in the resulting code; we record improvements in cyclomatic complexity and speedups on a number of representative benchmarks. [ABSTRACT FROM AUTHOR]

A wireless sensor network was created to measure water-flow rate in a fire hose. An integrated electronic piezoelectric accelerometer was chosen as the sensor to measure the flow rate based on the vibrations generated by water flowing through a fire hose close to the hose nozzle. These sensors are small, lightweight, and they can attach to the outside of the hose, not obstructing the water's flow path. A relationship between the dominant-frequency metric and the flow rate was applied and used to determine real-time water flow in a fire hose critical for improving fireground situational awareness. A nearly monotonic relationship of flow rate to the dominant frequency was established and then used in a custom graphical user interface for quick, real-time, visual referencing by fire personnel of flow rate in a fire hose. While more work is needed, such as improved physical robustness of the sensor-node assembly and increased robustness of the signal metric, this preliminary study shows the potential of a "smart" fire hose for improved situational awareness during a fire attack. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine the association between 'trouble sleeping', alcohol intake, hot flashes, and quality of life (QOL) in early-stage breast cancer survivors attending the Sydney Cancer Survivorship Clinic (SCSC). Methods: Survivors who had completed primary adjuvant treatment completed questionnaires assessing the following: symptoms, QOL (mean global score on FACT-G), and alcohol intake (drinks per day for past week), on the first visit to SCSC. Trouble sleeping and hot flashes were scored from 0 (no trouble at all) to 10 (worst I can imagine), with scores ≥ 4 classified as at least moderate and ≥ 7 severe. Results: 238 breast cancer survivors attended SCSC from September 2013 to May 2019, with data available for 227 (median age 53 years; 70% on endocrine therapy). Trouble sleeping was at least moderate in 54% and severe in 19%. 47% reported consuming alcohol (mean 4.9 drinks/week). Scores for trouble sleeping were no different between survivors reporting alcohol consumption and not (mean 4.13 vs. 3.6; p = 0.17). Survivors reporting at least moderate trouble sleeping (vs. less than moderate) were no more likely to drink alcohol (OR 1.74, 95% CI 0.96–3.14, p = 0.067) but had poorer mean QOL scores (69.1 vs. 78.3; p = 0.0006). Survivors reporting at least moderate hot flashes (vs. less than moderate) were more likely to report at least moderate trouble sleeping (OR 3.78, 95% CI 2.02–6.71, p < 0.0001) and had worse mean QOL scores (68 vs. 78; p = 0.001). Conclusion: Trouble sleeping is common amongst breast cancer survivors and associated with hot flashes and poorer QOL, but not with self-reported alcohol consumption. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD pathology. Our interest in the life cycle of HTT led us to consider the development of high-affinity small-molecule binders of HTT oligomerized/amyloid-containing species that could serve as either cellular and in vivo imaging tools or potential therapeutic agents. We recently reported the development of PET tracers CHDI-180 and CHDI-626 as suitable for imaging mHTT aggregates, and here we present an in-depth pharmacological investigation of their binding characteristics. We have implemented an array of in vitro and ex vivo radiometric binding assays using recombinant HTT, brain homogenate-derived HTT aggregates, and brain sections from mouse HD models and humans post-mortem to investigate binding affinities and selectivity against other pathological proteins from indications such as Alzheimer's disease and spinocerebellar ataxia 1. Radioligand binding assays and autoradiography studies using brain homogenates and tissue sections from HD mouse models showed that CHDI-180 and CHDI-626 specifically bind mHTT aggregates that accumulate with age and disease progression. Finally, we characterized CHDI-180 and CHDI-626 regarding their off-target selectivity and binding affinity to beta amyloid plaques in brain sections and homogenates from Alzheimer's disease patients. [ABSTRACT FROM AUTHOR]

Chip-to-chip and world-to-chip fluidic interconnections are paramount to enable the passage of liquids between component chips and to/from microfluidic systems. Unfortunately, most interconnect designs add additional physical constraints to chips with each additional interconnect leading to over-constrained microfluidic systems. The competing constraints provided by multiple interconnects induce strain in the chips, creating indeterminate dead volumes and misalignment between chips that comprise the microfluidic system. A novel, gasketless superhydrophobic fluidic interconnect (GSFI) that uses capillary forces to form a liquid bridge suspended between concentric through-holes and acting as a fluid passage was investigated. The GSFI decouples the alignment between component chips from the interconnect function and the attachment of the meniscus of the liquid bridge to the edges of the holes produces negligible dead volume. This passive seal was created by patterning parallel superhydrophobic surfaces (water contact angle ≥ 150°) around concentric microfluidic ports separated by a gap. The relative position of the two polymer chips was determined by passive kinematic constraints, three spherical ball bearings seated in v-grooves. A leakage pressure model derived from the Young–Laplace equation was used to estimate the leakage pressure at failure for the liquid bridge. Injection-molded, Cyclic Olefin Copolymer (COC) chip assemblies with assembly gaps from 3 to 240 µm were used to experimentally validate the model. The maximum leakage pressure measured for the GSFI was 21.4 kPa (3.1 psig), which corresponded to a measured mean assembly gap of 3 µm, and decreased to 0.5 kPa (0.073 psig) at a mean assembly gap of 240 µm. The effect of radial misalignment on the efficacy of the gasketless seals was tested and no significant effect was observed. This may be a function of how the liquid bridges are formed during the priming of the chip, but additional research is required to test that hypothesis. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95th percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation. [ABSTRACT FROM AUTHOR]

Temperature is among the critical determinants of the physiology of fishes and other heterotherms throughout the life history. Temperatures outside of the optimal range distress embryonic and larval development with untoward consequences later in life. To understand the effect of high temperature on embryogenesis and organogenesis, the commercially important rohu carp (Labeo rohita) was chosen. Rohu embryos and larvae were reared at four different temperatures (30, 32, 34, and 36 °C), and indices of their hatching, development, and mortality were observed throughout early development. Embryos exposed to 30 and 32 °C showed normal development with highest rates of hatching success. Embryos at 34 °C displayed evidence of damaged zygotes, cellular deformities, damaged yolk sac coupled with shortest incubation time, and the lowest rates of hatching success. No hatching was observed at 36 °C, and these embryos displayed coagulated organs, dark yolk sac, irregular segmentation, and pustules. Larvae of rohu exposed to 34 and 36 °C showed developmental deformities (fusion in the eye, axial curvature, yolk sac ulceration, blood coagulation, tail shortening, and ulceration) and minimal survival. Our results suggest that optimal temperature of rohu embryo and larvae is 30–32 °C or lower; higher temperatures disrupt embryonic metabolism and physiology, resulting in aberrant and unsuccessful early development. [ABSTRACT FROM AUTHOR]

We give a construction of general holomorphic quarter BPS operators in N = 4 SYM at weak coupling with U(N) gauge group at finite N. The construction employs the Möbius inversion formula for set partitions, applied to multi-symmetric functions, alongside computations in the group algebras of symmetric groups. We present a computational algorithm which produces an orthogonal basis for the physical inner product on the space of holomorphic operators. The basis is labelled by a U(2) Young diagram, a U(N) Young diagram and an additional plethystic multiplicity label. We describe precision counting results of quarter BPS states which are expected to be reproducible from dual computations with giant gravitons in the bulk, including a symmetry relating sphere and AdS giants within the quarter BPS sector. In the case n ≤ N (n being the dimension of the composite operator) the construction is analytic, using multi-symmetric functions and U(2) Clebsch-Gordan coefficients. Counting and correlators of the BPS operators can be encoded in a two-dimensional topological field theory based on permutation algebras and equipped with appropriate defects. [ABSTRACT FROM AUTHOR]

Subterranean radioiodine contamination at the Hanford Site in Washington State is believed to be present as iodide, iodate, and organo-I species, with iodate being the predominant form. Because these species have different sediment-sorption characteristics, understanding their distribution is important for developing an accurate understanding of iodine migration in the subsurface. Herein, we report a novel, rapid technique for simultaneous iodine speciation (iodide/iodate) and isotopic ratio (129I/127I) measurements using ion chromatography (IC) joined with collision/reaction cell inductively coupled plasma mass spectrometry (ICP-MS), collectively referred to as IC-ICP-MS. This approach employs online dynamically regenerated eluent suppression post chromatographic separation of the samples and collision cell technology, with pure oxygen as a collision gas for the active suppression of 129Xe (which naturally exists in the argon supplied to the ICP source) to rapidly (< 15 min) achieve precise and reproducible results. Speciated standard reference materials yielded detection limits for 127I of approximately 23.8 ng/L for iodate and 24.3 ng/L for iodide, and for 129I of approximately 1.81 ng/L for iodate and 2.62 ng/L for iodide. The method was demonstrated by analyzing groundwater samples from six wells from 129I-contaminated regions of the Hanford Site; iodate was the primary species for both 127I and 129I. Small quantities of 127I-iodide were also detected in most of the samples, but all 129I-iodide results were below the detection limit. An interference from molybdenum prevented the estimation of organo-iodine concentrations but did not affect the iodate and iodide results. This new analytical capability will enable rapid, simultaneous characterization of speciated inorganic iodine in vadose zone sediments and groundwater samples at levels below the US federal drinking water standard for 129I of 1 pCi/L (~ 5.6 ng/L). [ABSTRACT FROM AUTHOR]

Connectivity is fundamentally important for shaping the resilience of complex human and natural networks when systems are disturbed. Ecosystem resilience is, in part, shaped by the spatial arrangement of habitats, the permeability and fluxes between them, the stabilising functions performed by organisms, their dispersal traits, and the interactions between functions and stressor types. Controlled investigations of the relationships between these phenomena under multiple stressors are sparse, possibly due to logistic and ethical difficulties associated with applying and controlling stressors at landscape scales. Here we show that grazing performance, a key ecosystem function, is linked to connectivity by manipulating the spatial configuration of habitats in microcosms impacted by multiple stressors. Greater connectivity enhanced ecosystem function and reduced variability in grazing performance in unperturbed systems. Improved functional performance was observed in better connected systems stressed by harvesting pressure and temperature rise, but this effect was notably reversed by the spread of disease. Connectivity has complex effects on ecological functions and resilience, and the nuances should be recognised more fully in ecosystem conservation. [ABSTRACT FROM AUTHOR]

The objective of this study is to determine recent trends in use of robotics and laparoscopy for pediatric retroperitoneal lymph-node dissection (RPLND) in pediatric and non-pediatric hospitals. We conducted a retrospective cohort study using data from 29 hospitals in the Pediatric Health Information System (PHIS), and data from 14 states in the State Inpatient Databases (SID), between 2008 and 2014. The study population was comprised of patients aged ≥ 10 years undergoing RPLND, with an inpatient diagnosis of testicular or paratesticular cancer, based on international classification of disease (ICD) codes. Robotic approach was identified by the presence of an ICD procedure code modifier. During the study period, a total of 90 RPLNDs were performed in pediatric hospitals (median patient age 16 years). Of these, 4 (4.4%) were performed robotically. A total of 3120 RPLNDs were performed in non-pediatric hospitals (median patient age: 32 years). Among these, 269 (8.6%) were performed robotically, with an increasing trend in the use of robotic RPLND (adjusted annual increase in probability of undergoing robotic vs. open procedure: 16%; 95% CI 8–24). Undergoing robotic RPLND was associated with a reduction in postoperative length of stay of 3.5 days (95% CI 2.9, 4.1). Open surgical approaches comprise the vast majority of RPLNDs performed at pediatric hospitals. This is in contrast with trends in non-pediatric hospitals where robotic RPLND is being increasingly utilized. Future research is necessary to investigate this discrepancy in adopting minimally invasive techniques for RPLND in pediatric centers. [ABSTRACT FROM AUTHOR]

Coral reefs have been subject to mass coral bleaching, potentially causing rapid and widespread degradation of ecosystem services that depend on live coral cover, such as fisheries catch. Fisheries species in tropical waters associate with a wide range of habitats, so assessing the dependency of fisheries on coral reefs is important for guiding fishery responses to coral reef degradation. This study aimed to determine how fisheries catches associate with coral reefs in Queensland, Australia. Queensland's largest fisheries did not target fish associated with reefs, but specific sectors, particularly aquarium fisheries and commercial fisheries in the mid to northern region had a high dependence on species that use coral reefs. Regions that had a greater relative area of coral reefs had higher catches of species that depend on live coral, suggesting that coral area could be used to predict the sensitivity of a jurisdiction's fisheries to bleaching. Dynamic analysis of stock trends found that coral trout and red throat emperor, the two largest species by catch for the reef line fishery, were at risk of overfishing if habitat loss caused declines in stock productivity. Management of fisheries that are highly dependent on reefs may need to adapt to declining productivity, but further research to support ongoing reforms in Queensland's fisheries is needed to quantitatively link reef degradation to stock production parameters is needed. [ABSTRACT FROM AUTHOR]

Individuals with intellectual and developmental disabilities (I/DD) may experience greater risk of sexually transmitted infections, higher rates of sexual abuse, and decreased sexual health knowledge, emphasizing the need for accessible, comprehensive sexual health education. The purpose of this scoping review was to identify the extent and nature of sexual health education interventions among individuals with I/DD ages 15–24 years. Six studies were included in the review. They investigated sexual health interventions for individuals with autism spectrum disorder and mild I/DD, covered a wide range of topics (e.g. puberty, healthy relationships), included multiple learning activities (e.g. illustrations, activity-based learning), and measured behavior and sexual health knowledge outcomes. Future research is needed in this area to assess intervention effectiveness. [ABSTRACT FROM AUTHOR]

This paper presents a new technique for introducing and tuning parallelism for heterogeneous shared-memory systems (comprising a mixture of CPUs and GPUs), using a combination of algorithmic skeletons (such as farms and pipelines), Monte–Carlo tree search for deriving mappings of tasks to available hardware resources, and refactoring tool support for applying the patterns and mappings in an easy and effective way. Using our approach, we demonstrate easily obtainable, significant and scalable speedups on a number of case studies showing speedups of up to 41 over the sequential code on a 24-core machine with one GPU. We also demonstrate that the speedups obtained by mappings derived by the MCTS algorithm are within 5–15% of the best-obtained manual parallelisation. [ABSTRACT FROM AUTHOR]

The Generic Reusable Parallel Pattern Interface (GrPPI) is a very useful abstraction over different parallel pattern libraries, allowing the programmer to write generic patterned parallel code that can easily be compiled to different backends such as FastFlow, OpenMP, Intel TBB and C++ threads. However, rewriting legacy code to use GrPPI still involves code transformations that can be highly non-trivial, especially for programmers who are not experts in parallelism. This paper describes software refactorings to semi-automatically introduce instances of GrPPI patterns into sequential C++ code, as well as safety checking static analysis mechanisms which verify that introducing patterns into the code does not introduce concurrency-related bugs such as race conditions. We demonstrate the refactorings and safety-checking mechanisms on four simple benchmark applications, showing that we are able to obtain, with little effort, GrPPI-based parallel versions that accomplish good speedups (comparable to those of manually-produced parallel versions) using different pattern backends. [ABSTRACT FROM AUTHOR]

Developing countries are far more vulnerable to climate change impacts than industrialised countries. Most of the world's poor live in South Asia where they have limited livelihood options that have become even narrower in recent years, indicating a need for alternative income-generating options. Mud crabs (Scylla spp.) are considered to have promising prospects in different parts of the world including Bangladesh, a well-known region for its vulnerability to climate change. At present, this fishery has become a growing venture in coastal Bangladesh, primarily due to the potential of the export market and availability of seed locally. This study included a calculation of the Human Development Index linked to mud crab fishery (HDIMCF) and a strengths, weaknesses, opportunities and threats (SWOT) analysis to clarify the present status of and strategic directions for the mud crab fishery, for the first time. Results revealed an intermediate level of development of mud crab aquaculture, indicating potential alternative livelihood opportunities for vulnerable coastal communities. The SWOT analysis revealed that positive factors, both internal (strengths) and external (opportunities), predominate over negative factors (weaknesses and threats) and that the fishery can be an alternative livelihood option for vulnerable coastal communities. Despite noticeable diversification of the mud crab fishery, dependence on wild seedstock and possible over-exploitation in the wild appear to constrain sustainable development of the fishery. This study's findings suggest undertaking immediate wild crab stock assessment for determining current status of wild populations. Moreover, modification of the Government of Bangladesh's existing mud crab policy is needed to better meet growing demand and sustainability of the fishery. Recommendations of this study may be of help in guiding responsible integrated coastal fisheries management and policy. [ABSTRACT FROM AUTHOR]

A black tourmaline sample from Seagull batholith (Yukon Territory, Canada) was established to be a schorl with concentrations of Fe2+ among the highest currently found in nature (FeOtot ~ 18 wt.% and Fe2+ ~ 100% of Fetot) on the basis of a multi-analytical characterization through Mössbauer spectroscopy, electron microprobe, Laser-Ablation Inductively-Coupled-Plasma Mass-Spectrometry and single-crystal X-ray diffraction. From the crystal-chemical analysis, the following empirical formula is proposed: X(Na0.74□0.24K0.01Ca0.01)Σ1.00Y(Fe2+2.05Al0.92Ti0.02Mn0.01Zn0.01)Σ3.00Z(Al5.41Fe2+0.53Mg0.06)Σ6.00(Si6O18)(BO3)3V(OH)3W[(OH)0.46F0.41O0.13]Σ1.00, which can be approximated as NaY(Fe2+2Al)Z(Al5Fe2+)(Si6O18)(BO3)3(OH)3(OH,F). Compared to the formula of the ideal ordered schorl, NaY(Fe2+3)Z(Al6)(Si6O18)(BO3)3(OH)3(OH), the studied sample has a partial disorder of Fe2+ across the Y and the Z sites that can be expressed by the intracrystalline order–disorder reaction YAl + ZFe2+ → YFe2+ + ZAl. Such a partial cation disorder must be invoked to explain tourmaline structural stability because an ideal ordered schorl results in a large misfit between the < YFe2+–O > and < ZAl3+–O > mean bond lengths (that is, between the YO6 and ZO6 polyhedra). This misfit is reduced by introducing Al at Y (i.e., through the < Y–O > shortening) and Fe2+ at Z (i.e., through the < Z–O > lengthening). The result is that in tourmaline the site distribution of high Fe2+ concentrations is dictated by long-range structural constraints. [ABSTRACT FROM AUTHOR]

Fragmentation is a major driver of ecosystem degradation, reducing the capacity of habitats to provide many important ecosystem services. Mangrove ecosystem services, such as erosion prevention, shoreline protection and mitigation of climate change (through carbon sequestration), depend on the size and arrangement of forest patches, but we know little about broad-scale patterns of mangrove forest fragmentation. Here we conduct a multi-scale analysis using global estimates of mangrove density and regional drivers of mangrove deforestation to map relationships between habitat loss and fragmentation. Mangrove fragmentation was ubiquitous; however, there are geographic disparities between mangrove loss and fragmentation; some regions, like Cambodia and the southern Caribbean, had relatively little loss, but their forests have been extensively fragmented. In Southeast Asia, a global hotspot of mangrove loss, the conversion of forests to aquaculture and rice plantations were the biggest drivers of loss (>50%) and fragmentation. Surprisingly, conversion of forests to oil palm plantations, responsible for >15% of all deforestation in Southeast Asia, was only weakly correlated with mangrove fragmentation. Thus, the management of different deforestation drivers may increase or decrease fragmentation. Our findings suggest that large scale monitoring of mangrove forests should also consider fragmentation. This work highlights that regional priorities for conservation based on forest loss rates can overlook fragmentation and associated loss of ecosystem functionality. [ABSTRACT FROM AUTHOR]

Background: Precision therapeutics continuously make advances in cancer therapy, and a field of growing interest is the combination of targeted radionuclide therapy (TRNT) with potential radiosensitizing agents. This study evaluated whether the effects of in vitro TRNT, using the 177Lu-labeled anti-CD44v6 antibody AbN44v6, were potentiated by the novel stapled MDM2/X-p53 antagonist PM2. Materials and methods: Two wt p53 cell lines, HCT116 (colorectal carcinoma) and UM-SCC-74B (head and neck squamous cell carcinoma), expressing different levels of the target antigen, CD44v6, were used. Antigen-specific binding of 177Lu-AbN44v6 was initially verified in a 2D cell assay, after which the potential effects of unlabeled AbN44v6 on downstream phosphorylation of Erk1/2 were evaluated by western blotting. Further, the therapeutic effects of unlabeled AbN44v6, 177Lu-AbN44v6, PM2, or a combination (labeled/unlabeled AbN44v6 +/− PM2) were assessed in 3D multicellular tumor spheroid assays. Results: Radiolabeled antibody bound specifically to CD44v6 on both cell lines. Unlabeled AbN44v6 binding did not induce downstream phosphorylation of Erk1/2 at any of the concentrations tested, and repeated treatments with the unlabeled antibody did not result in any spheroid growth inhibition. 177Lu-AbN44v6 impaired spheroid growth in a dose-dependent and antigen-dependent manner. A single modality treatment with 20 μM of PM2 significantly impaired spheroid growth in both spheroid models. Furthermore, the combination of TRNT and PM2-based therapy proved significantly more potent than either monotherapy. In HCT116 spheroids, this resulted in a two- and threefold spheroid growth rate decrease for the combination of PM2 and 100 kBq 177Lu-AbN44v6 compared to monotherapies 14-day post treatment. In UM-SCC-74B spheroids, the combination therapy resulted in a reduction in spheroid size compared to the initial spheroid size 10-day post treatment. Conclusion: TRNT using 177Lu-AbN44v6 proved efficient in stalling spheroid growth in a dose-dependent and antigen-dependent manner, and PM2 treatment demonstrated a growth inhibitory effect as a monotherapy. Moreover, by combining TRNT with PM2-based therapy, therapeutic effects of TRNT were potentiated in a 3D multicellular tumor spheroid model. This proof-of-concept study exemplifies the strength and possibility of combining TRNT targeting CD44v6 with PM2-based therapy. [ABSTRACT FROM AUTHOR]

Background Context: Laminoplasty and laminectomy with fusion are two common procedures for the treatment of cervical spondylotic myelopathy. Controversy remains regarding the superior surgical treatment.Purpose: To compare short-term follow-up of laminoplasty to laminectomy with fusion for the treatment of cervical spondylotic myelopathy.Study Design/setting: Retrospective review comparing all patients undergoing surgical treatment for cervical spondylotic myelopathy by a single surgeon.Patient Sample: All patients undergoing laminoplasty or laminectomy with fusion by a single surgeon over a 5-year period (2007-2011).Outcome Measures: Cervical alignment and range of motion on pre- and post-operative radiographs and clinical outcome measures including Japanese Orthopaedic Association (JOA) scores, neck disability index (NDI), short form-12 mental (SF-12M) and physical (SF-12P) composite scores and visual analog pain scores for neck (VAS-N) and arm (VAS-A).Methods: Patients undergoing laminoplasty or laminectomy with fusion by a single surgeon were reviewed. Cohorts of 41 laminoplasty patients and 31 laminectomy with fusion patients were selected based on strict criteria. The cohorts were well matched based on pre-operative clinical scores, radiographic measurements, and demographics. The average follow-up was 19.2 months for laminoplasty and 18.2 months for laminectomy with fusion. Evaluated outcomes included Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), short form-12 (SF-12), visual analog pain scores (VAS), cervical sagittal alignment, cervical range of motion, length of stay, cost and complications.Results: The improvement in JOA, SF-12 and VAS scores was similar in the two cohorts after surgery. There was no significant change in cervical sagittal alignment in either cohort. Range-of-motion decreased in both cohorts, but to a greater degree after laminectomy with fusion. C5 nerve root palsy and infection were the most common complications in both cohorts. Laminectomy with fusion was associated with a higher rate of C5 nerve root palsy and overall complications. The average hospital length of stay and cost were significantly less with laminoplasty.Conclusions: This study provides evidence that laminoplasty may be superior to laminectomy with fusion in preserving cervical range of motion, reducing hospital stay and minimizing cost. However, the significance of these differences remains unclear, as laminoplasty clinical outcome scores were generally comparable to laminectomy with fusion. [ABSTRACT FROM AUTHOR]

The use of global navigation satellite systems (GNSS) to monitor the deformations and displacements of structures is well established. Traditionally, research has focussed on the movements of individual locations upon such a structure. In this study, survey-grade global positioning system (GPS) receivers were placed at nine locations upon the bridge and on the tops of the four support towers, and GNSS (GPS, GLONASS) receivers at five key locations on the two suspension cables of the Severn Suspension Bridge. Data were gathered at 10 Hz and 20 Hz, positioned relative to reference GNSS receivers located nearby, over a period of 4 days. This resulted in a dataset allowing the daily movements of the bridge due to applied loading to be measured to millimetre precision. This paper describes the layout of the survey, as well as the movements of the various GNSS antenna locations relative to each other in terms of 3D displacements as well as the frequencies of the movements. A correlation function is developed and applied on the kinematic GPS data, illustrating the synchronised and relative movements of these locations. Correlation between the movements of the bridge's support towers and suspension cables is illustrated, and conclusions about this development with respect to the potential application of the technique as part of a Structural Health Monitoring (SHM) system are drawn. [ABSTRACT FROM AUTHOR]

Community-based fisheries management that integrates local knowledge and existing user rights is often seen as a solution to the failures of top-down fisheries management in the Pacific. In Roviana Lagoon, Western Solomon Islands, a network of community-based marine protected areas (MPAs) was established in the early 2000s to conserve declining populations of bumphead parrotfish (Bolbometopon muricatum) and other locally valuable fish species such as humphead wrasse (Cheilinus undulatus). We aimed to evaluate the success of these protected areas at preventing declines of B. muricatum and C. undulatus. We conducted 27 underwater visual census (UVC) surveys at permanent passage and outer reef monitoring sites in Roviana Lagoon in 2018 and compared our findings with results from 72 UVC surveys that we had conducted at the same sites 18 yrs earlier. We also interviewed Roviana spearfishers about their maximum nightly B. muricatum catches from 2018, the early 2000s and the 1980s. Abundances of all B. muricatum and C. undulatus sighted on UVC surveys declined by 62% and 57%, respectively, between 2000 and 2018, and abundances of adult B. muricatum and C. undulatus declined by 78% and 72%, respectively, over the same period. Using a joint model of B. muricatum abundance and its reported maximum catch, we estimated that in 2018 the population of B. muricatum was 8% of its 1980's abundance. By modelling projected rates of decline over three generations, we show that populations of B. muricatum and C. undulatus in Roviana Lagoon meet the IUCN Red List thresholds for Critically Endangered (CR). The probable causes of these declines are sustained fishing pressure, poor enforcement of community-based management measures and loss of fish nursery habitats due to logging. Our findings suggest urgent co-management of the ridge-to-reef system is needed to prevent further fish population declines in Roviana Lagoon. [ABSTRACT FROM AUTHOR]