Assessing the critical material constraints on low carbon infrastructure transitions

We present an assessment method to analyze whether the disruption in supply of a group of materials endangers the transition to low-carbon infrastructure. We define criticality as the combination of the potential for supply disruption and the exposure of the system of interest to that disruption. Low-carbon energy depends on multiple technologies comprised of a multitude of materials of varying criticality. Our methodology allows us to assess the simultaneous potential for supply disruption of a range of materials. Generating a specific target level of low-carbon energy implies a dynamic roll-out of technology at a specific scale. Our approach is correspondingly dynamic, and monitors the change in criticality during the transition towards a low-carbon energy goal. It is thus not limited to the quantification of criticality of a particular material at a particular point in time. We apply our method to criticality in the proposed UK energy transition as a demonstration, with a focus on neodymium use in electric vehicles. Although we anticipate that the supply disruption of neodymium will decrease, our results show the criticality of low carbon energy generation increases, as a result of increasing exposure to neodymium-reliant technologies. We present a number of potential responses to reduce the criticality through a reduction in supply disruption potential of the exposure of the UK to that disruption

Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine.

Giardia lamblia is a highly prevalent yet understudied protistan parasite causing significant diarrheal disease worldwide. Hosts ingest Giardia cysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host are largely inferred from laboratory culture and thus may not mirror Giardia physiology in the host. Here, we have developed bioluminescent imaging (BLI) to directly interrogate and quantify the in vivo temporospatial dynamics of Giardia infection, thereby providing an improved murine model to evaluate anti-Giardia drugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine nonuniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high density contributes to the initiation of encystation in laboratory culture. We suggest that these high-density in vivo foci of colonizing and encysting Giardia likely result in localized disruption to the epithelium. This more accurate visualization of giardiasis redefines the dynamics of the in vivo Giardia life cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host. IMPORTANCEGiardia is a single-celled parasite causing significant diarrheal disease in several hundred million people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics of Giardia infections in the host has remained limited and largely inferred from laboratory culture. To better understand Giardia physiology and colonization in the host, we developed imaging methods to quantify Giardia expressing bioluminescent physiological reporters in two relevant animal models. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. We also show that high parasite density contributes to encystation initiation

S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse

Progressive hearing loss is very common in the population but we still know little about the underlying pathology. A new spontaneous mouse mutation (stonedeaf, stdf ) leading to recessive, early-onset progressive hearing loss was detected and exome sequencing revealed a Thr289Arg substitution in Sphingosine-1-Phosphate Receptor-2 (S1pr2). Mutants aged 2 weeks had normal hearing sensitivity, but at 4 weeks most showed variable degrees of hearing impairment, which became severe or profound in all mutants by 14 weeks. Endocochlear potential (EP) was normal at 2 weeks old but was reduced by 4 and 8 weeks old in mutants, and the stria vascularis, which generates the EP, showed degenerative changes. Three independent mouse knockout alleles of S1pr2 have been described previously, but this is the first time that a reduced EP has been reported. Genomic markers close to the human S1PR2 gene were significantly associated with auditory thresholds in the 1958 British Birth Cohort (n = 6099), suggesting involvement of S1P signalling in human hearing loss. The finding of early onset loss of EP gives new mechanistic insight into the disease process and suggests that therapies for humans with hearing loss due to S1P signalling defects need to target strial function

Urinary Proteomics to Support Diagnosis of Stroke

Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69), compared to controls (n = 33), and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004) or 35 biomarkers (nominal p-value <0.01). When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (−0.30 to 1.25) in cases compared to −1.04 (IQR −1.86 to −0.09) in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

Моделі процесів захисту цілісності інформаційних об’єктів з використанням коду умовних лишків. Алгоритм нулізації

The models of processes of defense of integrity of information’s holding object with application of code of conditional tailings which provide high probabilities of exposure of violations of integrity and correction of the exposed curvatures are examined

Changes in Seizure Frequency and Test-Retest Scores on the Wechsler Adult Intelligence Scale

Test-retest performance on the Wechsler Adult Intelligence Scale (WAIS) of two groups of adult epilepsy patients are presented and compared. In one group, Seizures Improved (SI) group, seizure frequency had decreased during the test-retest interval, and in the other group, Seizures Unimproved (SU) group, the number of seizures had either increased or stayed the same over the test-retest interval. The SI group showed a significant test-retest improvement on WAIS Verbal IQ, Performance 1Q, and Full Scale IQ, as well as on eight of 11 WAIS subtests. In comparison, the SU group showed significant increases only on the Performance IQ and Object Assembly subtest. Furthermore, differences between the two groups were observed in the pattern of test-retest changes seen on the Performance measures relative to the Verbal measures. The results suggest that change in seizure frequency is one of the factors associated with test-retest changes in the intellectual functioning of epilepsy patients. RÉSUMÉ Les rÉsultats obtenus À I‘Échelle de WAIS (Wechsler Adults Intelligence Scale) a partir d'une passation I (test) et d'une passation II (retest) chez deux groupes d'Épileptiques adultes sont prÉsentÉs et compares: (a) Dans un groupe la frequence des crises a diminue dur-ant I'intervalle “test-retest” (c'est a dire dans I'inter-valle separant la passation I (test) de la passation II (retest): Groupe des crises ameliorees (SI: seizures improved), (b) Dans l'autre groupe le nombre des crises au contraire a augmente ou bien est reste iden-tique au cours de I'intervalle “test-retest”: Groupe des crises non ameliorees (SU: seizures unimproved). Le groupe des “crises ameliorees” montre une amelioration significative tant sur le plan du QIV (quotient de I'echelle verbale), que du QIP (quotient de I'echelle performance) et du QIG (quotient global), ainsi que de 8 des subtests parmi les onze que contien I'echelle. En comparaison le groupe des “crises non ameliorees” ne montre une amelioration significative qu'au niveau du QIP et en particulier sur le subtest d'assemblage d'ob-jets (celui-ci faisant partie de I'echelle performance). De plus, on observe entre les deux groupes des differences du “type” des modifications entrainees par la situation “test-retest”, sur les rÉsultats obtenus a I'echelle performance et ceux obtensus a I'echelle verbale. Ces rÉsultats permettent de suggerer que, dans le fonctionnement intellectuel des sujets epileptiques, les changements dans la frequence des crises sont un des facteurs a mettre en correlation avec les changements observes a partir de la situation “test-retest”. RESUMEN Se compararon dos grupos de adultos con epilepsia por medio del rendimiento en dos tests de WAIS. En un grupo, la frecuencia de los ataques habia disminuido en el intervalo entre el primer test y el segundo [grupo con mejoria (SI)], mientras que en el otro el mimero de crisis no habia variado o habia au-mentado [grupo sin mejoria (SU)]. El grupo SI mostro una mejoria en laescala verbal CI, en la realizacion CI, en la escala total de CI y en los subtests WAIS. En comparacion, el grupo SU solo mostro un aumento significativo en la realizacion CI y en el subtest de Reunion de Objetos. Ademas, se observaron diferen-cias entre los dos grupos en lo que respecta a la prim-era y a la segunda prueba en la realizacion de las medidas verbales. Los resultados sugieren que los cambios en la frecuencia de los ataques juegan un papel en lo que respecta a funciÓn intelectual cuando se compara el primer WAIS con el segundo. ZUSAMMENFASSUNG Test und Retest Ergebnisse im WAIS von 2 Gruppen erwachsener Epileptiker werden dargestellt und ver-glichen. In einer Gruppe hatte die Anfallshaufigkeit wahrend des Test-Retest-Intervalls abgenommen– verbesserte Gruppe (SI)–und in einer anderen Gruppe war die Anfallshaufigkeit entweder gestiegen oder gleich geblieben wahrend des Test-Retest-Intervalls– unveranderte Gruppe (SU). Die SI-Gruppe zeigte signifikante Verbesserung zwischen Test und Retest im Verbal-IQ des WAIS, im Handlungsteil und im Gesamt-IQ ebenso wie in 8 von 11 WAIS Subtests. Im Vergleich hierzu zeigte die SU-Gruppe signifikante Verbesserung nur im Handlungs-IQ und im Objekte-zuordnungs-Subtest. Weiterhin wurden Unterschiede zwischen den beiden Gruppen im Muster der Test-Retest-Veranderungen im Verhaltnis des Handlung-steils zum Verbalteil bemerkt. Die Ergebnisse lassen vermuten, dalJ die Veranderung der Anfallshaufigkeit einer der Faktoren ist, der hinsichtlich der in-tellektuellen Funktion anfallskranker Patienten Bezie-hungen zu den Veranderungen des Test-Retest-Ergeb-nis aufweist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65457/1/j.1528-1157.1981.tb04334.x.pd

Studying Public Health Law::Principles, Politics, and Populations as Patients

Public health law is firmly establishing itself as a crucial area of scholarly inquiry. Its vital importance has been sharply underscored following the outbreak of COVID-19, in response to which we have seen the institution of extreme legal measures—suchas the UK’s Coronavirus Act 2020—in efforts to control and contain the spread ofthe disease. The pandemic has also starkly exposed the complex nature of the regulatory challenges, nationally, internationally, and globally, to which such public health problems give rise. In approaching these, and other questions concerning the public’s health, such as non-communicable disease, public health law, as a field, brings notable distinctive features: these include a practical focus on populations, institutions, the prevention of ill health, protection of good health, and thepromotion of positive states of well-being; and concomitant critical approaches rooted in theories of social justice as contrasted with more narrow biomedical ethics. Such features make it in some senses atypical territory within the field of health law. Furthermore, the inherent role of political institutions places law conceptually within public health in a way that may be seen as distinguishable from law’s relationship with clinical medicine. This chapter explains how the broad reach and distinct features of public health require a commensurately broad approach to conceptualising public health law, and how distinct practical and theoretical features may be integrated into academic public health law. It also shows how public health law, with its distinct conceptualisations concerning ‘the body’ of medical jurisprudence, can both challenge and enrich medico-legal studies, and bring important perspectives within the broader field of health law

Health service utilization patterns of primary care patients with osteoarthritis

Contains fulltext : 53455.pdf ( ) (Open Access)BACKGROUND: To assess factors associated with visits to GPs, orthopaedists, and non-physician practitioners of complementary medicine (alternative practitioners) by primary care patients with osteoarthritis (OA). METHODS: Cross-sectional survey among 1250 consecutively addressed patients from 75 primary care practices in Germany. All patients suffered from OA of the knee or hip according to ACR criteria. They received questionnaires collecting sociodemographic data, data about health service utilisation, prescriptions, comorbidities. They also included established instruments as the Arthritis Impact Measurement Scale (AIMS2-SF) to assess disease-specific quality of life and the Patient Health Questionnaire (PHQ-9) to assess depression. Hierarchical stepwise multiple linear regression models were used to reveal significant factors influencing health service utilization. RESULTS: 1021 of 1250 (81.6%) questionnaires were returned. Nonrespondents did not differ from participants. Factors associated with health service use (HSU) varied between providers of care. Not being in a partnership, achieving a high score on the PHQ-9, increased pain severity reflected in the "symptom" scale of the AIMS2-SF, and an increased number of drug prescriptions predicted a high frequency of GP visits. The PHQ-9 score was also a predictor for visits to orthopaedists, as were previous GP contacts, a high score in the "symptom" scale as well as a high score in the "lower limb scale" of the AIMS2-SF. Regarding visits to alternative practitioners, a high score in the AIMS -"social" scale was a positive predictor as older people were less likely to visit them. CONCLUSION: Our results emphasize the need for awareness of psychological factors contributing to the use of health care providers. Addressing the revealed factors associated with HSU appropriately may lead to decreased health care utilization. But further research is needed to assess how this can be done successfully

Gastrointestinal Stromal Tumours treated before and after the advent of c-kit immunostaining

<p>Abstract</p> <p>Background</p> <p>Recently developed immunohistochemical markers have revolutionised the classification of gastrointestinal stromal tumours (GISTs) whilst tyrosine kinase inhibitors (imatinib) have had a significant impact on the treatment of advanced tumours. We review the clinicopathological features of previously resected mesenchymal tumours of the gastrointestinal tract in our institution to 1) reclassify the histological diagnosis of those stained prior to c-kit availability; 2) perform survival analysis to identify prognostic factors, and 3) to consider the implications for patients.</p> <p>Methods</p> <p>Clinicopathological records of patients with a diagnosis of mesenchymal tumours treated between May 1992 and April 2007 were reviewed.</p> <p>Results</p> <p>82 patients were reviewed. 26 (32%) were reclassified as GISTs following c-kit immunostaining and a further 14 patients were treated for GIST up to April 2007 (Total: 40 patients; 21 males and 19 females, mean age 67, range 30-92 years). 36 (90%) underwent complete resection. 5-year survival of patients with GIST alone was 80%. Females had a better median survival (M: F 43 months: 73 months).</p> <p>Conclusions</p> <p>The availability of c-kit staining allowed 32% of previously diagnosed mesenchymal tumours to be reclassified as GISTs. This may have implications for the follow-up of patients diagnosed prior to the availability of this method.</p