Anomalous density fluctuations in a strange metal.

A central mystery in high-temperature superconductivity is the origin of the so-called strange metal (i.e., the anomalous conductor from which superconductivity emerges at low temperature). Measuring the dynamic charge response of the copper oxides, [Formula: see text], would directly reveal the collective properties of the strange metal, but it has never been possible to measure this quantity with millielectronvolt resolution. Here, we present a measurement of [Formula: see text] for a cuprate, optimally doped Bi2.1Sr1.9CaCu2O8+x (Tc = 91 K), using momentum-resolved inelastic electron scattering. In the medium energy range 0.1-2 eV relevant to the strange metal, the spectra are dominated by a featureless, temperature- and momentum-independent continuum persisting to the electronvolt energy scale. This continuum displays a simple power-law form, exhibiting q2 behavior at low energy and q2/ω2 behavior at high energy. Measurements of an overdoped crystal (Tc = 50 K) showed the emergence of a gap-like feature at low temperature, indicating deviation from power law form outside the strange-metal regime. Our study suggests the strange metal exhibits a new type of charge dynamics in which excitations are local to such a degree that space and time axes are decoupled.

Plasmon excitation and subsequent isomerization dynamics in naphthalene and azulene under fast proton interaction.

The interaction of fast protons (velocity between 1.41 and 2.4 a.u.) with naphthalene and azulene is investigated as a model of an ion-polycyclic aromatic hydrocarbon interaction system. Production of various intact and fragment ions in coincidence with electron emission, electron transfer to projectile, or both is analyzed. The two targets being isomers, the rather obvious similarity in the fundamental ion-molecule collision energetics is quantitatively verified. The fast isomerization processes of cationic azulene are observed to be influencing its further dissociation channels such as C2H2 and H eliminations. A first ever attempt is presented here wherein single plasmon excitation in conjunction with isomerization dynamics is reported. Evidence from dication evaporation energetics is used to invoke the double plasmon excitation model. A model based on the multiplasmon resonance explains the observed proton velocity dependence of double to single ionization cross sections. Moreover an attempt is made to reinforce the proposition of double plasmon excitation by explaining the observed suppression of neutral H loss from dications as opposed to monocations.

Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10-5 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10-14 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project.

The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante-mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board-certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo-preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine-specific biobank with extensive clinical phenotyping ante- and post-mortem. The tissues in the biobank are intended for community-wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease.

Genetic contribution of CYP1A1 variant on treatment outcome in epilepsy patients: a functional and interethnic perspective.

CYP1A1 gene is involved in estrogen metabolism, and previously, we have reported association of variant rs2606345 with altered anti-epileptic drugs (AED) response in North Indian women with epilepsy (WWE). The present study aims to replicate the pharmacogenetic association, perform functional characterization and study its distribution within ethnically diverse Indian population. The variant was genotyped in 351 patients to assess the pharmacogenetic association and 552 healthy individuals belonging to 24 different ethnic groups to examine the distribution in Indian population. We observed significant overrepresentation of 'A' allele and 'AA' genotype in poor responders in WWE at Bonferroni-corrected significance levels. The recessive allele was found to lower the promoter activity by ~70-80% which was further substantiated by thermally less stable hairpin formed by it (ΔTm=7 °C). Among all ethnic groups, west Indo-European (IE-W-LP2) subpopulation showed highest genotypic frequency of the variant making women from this community more prone to poor AED response. Our results indicate that rs2606345 influences drug response in WWE by lowering CYP1A1 expression.

Surface Collective Modes in the Topological Insulators Bi_{2}Se_{3} and Bi_{0.5}Sb_{1.5}Te_{3-x}Se_{x}.

We used low-energy, momentum-resolved inelastic electron scattering to study surface collective modes of the three-dimensional topological insulators Bi_{2}Se_{3} and Bi_{0.5}Sb_{1.5}Te_{3-x}Se_{x}. Our goal was to identify the "spin plasmon" predicted by Raghu and co-workers [Phys. Rev. Lett. 104, 116401 (2010)]. Instead, we found that the primary collective mode is a surface plasmon arising from the bulk, free carriers in these materials. This excitation dominates the spectral weight in the bosonic function of the surface χ^{"}(q,ω) at THz energy scales, and is the most likely origin of a quasiparticle dispersion kink observed in previous photoemission experiments. Our study suggests that the spin plasmon may mix with this other surface mode, calling for a more nuanced understanding of optical experiments in which the spin plasmon is reported to play a role.

Economic Hardships in Managing COVID-19 Patients in the Intensive Care Unit: A Retrospective Observational Study at a Tertiary Care Hospital in North India.

BACKGROUND: The information on healthcare expenditure is crucial to know the impact of the pandemic on public health budgets, thereby correctly managing the ongoing crisis and preparing for subsequent waves. OBJECTIVE: To estimate the length of stay and cost incurred on COVID-19 patients who died in the ICU. METHODS: It is a record-based descriptive study conducted on 76 deceased COVID-19 patients admitted to the ICU of a dedicated COVID-19 hospital (DCH) between April and October 2020. Central Government Health Services (CGHS) package rate list, Delhi-NCR, was used as a reference for the cost of the ICU bed, ventilator, investigations, and procedures. RESULTS: The median duration of stay in the hospital was 12 days, and in the ICU, it was eight days. The median total cost of managing the patient was 91,235.6 INR; of this, the median total cost for ICU stay per patient was 6,904 INR. The major proportion of total expenses was contributed by personal protective equipment (PPE) kits, an average of 11,091.33 INR per month. The median cost of stay in the ICU, on the ventilator, in the ward, and mean cost of investigations were higher among those with associated co-morbidities. CONCLUSION: Most elderly male with co-morbidities lost their battle after ventilator support in the ICU. Patients with co-morbidities and severe disease not only have a long duration of hospitalization and poor survival rate but also fetch an economic burden close to one lakh on the institute.

Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Surgical learning activities for house officers: do they improve the surgical experience?

OBJECTIVE: To ascertain whether house officers (HOs) attain a more satisfactory surgical rotation experience when they perform basic surgical learning activities. We also sought to establish how many and which learning activities HOs achieve and the effect on their surgical experience. METHODOLOGY: A questionnaire listing 20 learning activities and questions regarding satisfaction with an overall experience was disseminated to HOs in the UK and Ireland who had completed ≥3 months of surgical rotations. Satisfaction with surgical experience was dichotomised in order to perform logistic regression using R Studio software v0.98. RESULTS: The survey was completed by 150 respondents, with 26 % completing at least 10 basic surgical learning activities during their surgical rotation. On multivariate analysis, the completion of these learning activities was significantly associated with a satisfactory rotation experience (p < 0.001). Furthermore, the use of a checklist of surgical activities provided to HOs was associated with a significant increase in the performance of learning activities (p = 0.003). CONCLUSION: Surgical HOs who were informed about potential basic surgical learning activities that can be performed during their rotations performed significantly more of these activities. And these activities were associated with a significantly greater satisfaction with surgical rotations. Therefore, we recommend facilitating HOs completion of these activities as this will ensure that basic surgical competencies are achieved and that HOs will be more satisfied with their surgical experience.

Autistic features in young children with significant cognitive impairment: autism or mental retardation?

This review addresses the issues and challenges related to the differential diagnosis of autism in preschool children with significant cognitive impairment. Issues affecting differential diagnosis include the use of traditional diagnostic guidelines for preschoolers with developmental delays, developmental changes in behavioral characteristics, the involvement of cognitive factors in symptom expression, and the overlap between autism and mental retardation in individuals with significant cognitive impairment. The usefulness of autistic features for differential diagnosis is explored in terms of the core deficits of autism.

Thromboelastography: a reliable test?

The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra- and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modified TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P = not significant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a significant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modified TEG showed no change. Intra- and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P = NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability.

Intermittent claudication: a condition with underrated risks.

Intermittent claudication (IC) is a symptom of peripheral arterial occlusive disease (PAOD); it is subjective and therefore difficult to measure reliably. Both the WHO/Rose Questionnaire and the Edinburgh Questionnaire have been used widely, but they have a low sensitivity and therefore underestimate the true prevalence of IC. The addition of a clinical examination does not necessarily eliminate errors found on questionnaires alone. The single most important part of the physical examination to confirm a diagnosis of IC is the palpation of the patient's peripheral pulses, which alone appears to be more sensitive, but less specific, than the questionnaires. The most useful noninvasive test is the ankle-brachial pressure index (ABPI), and it has been suggested that a resting ABPI of 0.9 is up to 95% sensitive in detecting angiogram-positive disease, and almost 100% specific in identifying apparently healthy individuals. An ABPI of 0.9 or less is believed to be associated with 50% or greater vessel stenosis. The incidence of IC varies depending on the methodology used to define it, but there is a general pattern of a gradual increase in incidence up to the age of at least 70 years. For a chronic disease, the prevalence is a more relevant indicator of how common it is. The prevalence of IC is 3% to 6% in men aged 60 years and increases with age. The prevalence of asymptomatic PAOD may be as high as 20% in the adult population, using noninvasive testing. This is important because, as will be seen in later articles, PAOD, whether symptomatic or asymptomatic, is a serious risk factor for cardiovascular morbidity and mortality.

Predictors of early disease in the lower limbs.

Increasing age and male gender are unavoidable risk factors for peripheral arterial occlusive disease (PAOD). A number of studies have looked at classical risk factors for atherosclerosis, such as diabetes, hypertension, lipid abnormalities, and smoking, as well as some more recently identified associations, such as plasma fibrinogen levels, impaired glucose tolerance, and hyperhomocysteinemia. However, most "risk factors" are really associations. A causal relationship may only reasonably be firmly established if a prospective controlled study shows that removing the risk factor significantly alters the course of the disease, as with smoking. Smoking is probably the strongest risk factor for intermittent claudication (IC), but hyperhomocysteinemia also appears to be strongly associated with the development of PAOD. Moderate alcohol intake and regular physical exercise appear to have a protective effect. A genetic risk factor is suggested but not as yet confirmed. The magnitude of the association varies from odds ratios of 2 to 3 for smoking and diabetes. There is insufficient evidence for hyperhomocysteinemia, but the effect may be even greater. The association with hypertension and lipid abnormalities is surprisingly inconclusive.

Lower-extremity arteriosclerosis as a reflection of a systemic process: implications for concomitant coronary and carotid disease.

Peripheral arterial occlusive disease (PAOD), coronary artery disease (CAD), and cerebrovascular disease (CVD) are all manifestations of atherosclerosis or atherothrombosis, and therefore it is not surprising that the three conditions commonly occur together. Knowledge of the magnitude of co-existing cardiovascular disease and its prognosis is essential for the physician treating IC so that he can treat the local disease in its systemic context. The prevalence of CAD in patients with IC is 40% to 60%, although this may be asymptomatic and increases with the severity of the PAOD. Not surprisingly, the converse is also true; among individuals with CAD, the prevalence of PAOD is higher than in non-CAD individuals. The link between PAOD and CVD seems to be weaker than that with CAD, but again up to 60% of claudicants have some evidence of CVD. The prevalence of patients with CVD increases as the ABPI decreases. The evidence available from all of the relevant studies suggests that approximately 60% of patients with PAOD will have significant disease in the cardiac or cerebral circulation, and approximately 40% of patients with coronary disease or significant cerebral circulatory disease also will have PAOD.

The natural history of claudication: risk to life and limb.

Although a patient with intermittent claudication (IC) will fear progression to severe disease and amputation, this is a relatively rare outcome of claudication, with only 1% to 3% of claudicants ever requiring major amputation over a 5-year period. Indeed, in one study, 50% of claudicants became symptom free during 5 years' follow-up. All the new evidence over the last 40 years has not altered the impression that only about one fourth of patients with IC will ever significantly deteriorate, and that deterioration is most frequent during the first year after diagnosis (6 to 9%) compared with 2% to 3% per annum thereafter. Smoking is the most important risk factor for the progression of local disease in the legs, with an amputation rate 11 times greater in smokers than nonsmokers. Diabetes, male gender, and hypertension are also important risk factors for progression. Because cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial occlusive disease (PAOD) coexist, PAOD and IC should be regarded as a marker for increased risk from fatal and nonfatal cardiovascular event, and 2% to 4% of claudicants have a nonfatal cardiovascular event every year. The risk is higher in the first year after developing IC than in a long-standing stable claudicant, and the average claudicant is more likely to have a nonfatal myocardial infarction (MI) or stroke in the next year that of ever requiring a major amputation for his leg ischemia. The mortality in claudicants is 30% at 5 years, 50% at 10 years, and 70% at 15 years, without any clear decrease in these figures over the last 30 to 40 years. The mortality of claudicants is approximately two and a half times that of an age-matched general population.

Predicting which patients will develop chronic critical leg ischemia.

Although numerically far less than claudicants, patients with critical leg ischemia (CLI) demand a disproportionately large commitment both in medical effort and economically and represent the major workload for vascular surgical units. The incidence and prevalence of CLI is approximately 500 to 1,000/million/year. The risk factors for the development of CLI are largely the same as those for the progression of local disease in IC, the most important, apart from age, being smoking and diabetes. Major amputation is more common amongst claudicants who are heavy smokers and who continue to smoke, and although stopping smoking slows down the vascular changes and reduces the likelihood of symptomatic progression, it does not reduce the risk of major amputation over the following 2 to 3 years. Diabetic PAOD patients are about 10 times more likely to come to amputation than nondiabetic PAOD patients, and the prevalence of gangrene is 20 to 30 times higher in individuals with diabetes and PAOD compared with nondiabetics with PAOD. There is some evidence that most of these effects of risk factors are additive.

The fate of patients with critical leg ischemia.

In some highly specialized and aggressive units, 90% of patients with critical leg ischemia (CLI) will undergo some form of surgical or endovascular procedure; however, in most, the figure is nearer 50 to 60%. The primary amputation rate varies from around 10% to 40%. The mortality rate in these patients with standard therapy is around 20% at 1 year and between 40% and 70% at 5 years. Virtually all (95%) patients who present with ischemic gangrene, and 80% of those presenting with rest pain, are dead within 10 years. There appears to be a decline in overall major amputation rates associated with a corresponding increase in revascularizations. However, although technical advances may have resulted in a steadying or even decrease in amputations, comparisons of total amputations over a longer period suggest an increase, presumably attributable to an aging population. Some forward projections predict that major amputations will be doubled in the next 30 years.

Acute limb ischemia.

Although there is little information on the incidence of acute limb ischemia (ALI) in the general population, it is estimated to be 14 per 100,000 and to compose 10% to 16% of the vascular workload. Also, as surgical intervention has become an option for ALI, the numbers actually referred appear to be increasing. The two main causes of ALI are either an embolism or a thrombosis, and differentiation based on history and clinical examination alone may be clinically impossible in 10% to 15% of cases. However, with the advent of thrombolysis, the distinction between emboli and thrombotic occlusions has become less important from the point of view of management. The natural history of ALI has remained largely unchanged despite the advent of the Fogarty catheter and thrombolysis. Patients presenting with ALI continue to have a particularly severe short-term outlook both in terms of loss of the leg and mortality, with 30-day amputation rates of between 10% and 30% and a mortality rate of around 15%. A patient with an embolic cause for an ischemic leg is at a higher risk of death because of the associated underlying cardiac disease, whereas patients with a thrombotic cause are more likely to lose a limb. The fact that overall mortality rates after intervention for acute ischemia have not improved dramatically over the past 20 years no doubt reflects the severity of the underlying diseases in these high-risk patients.