Erratum: Ubiquitous Non-Majorana Zero-Bias Conductance Peaks in Nanowire Devices [Phys. Rev. Lett. 123, 107703 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.107703.

A comparison of self and proxy quality of life ratings for people with dementia and their carers: a European prospective cohort study.

Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.

Ubiquitous Non-Majorana Zero-Bias Conductance Peaks in Nanowire Devices.

We perform tunneling measurements on indium antimonide nanowire-superconductor hybrid devices fabricated for the studies of Majorana bound states. At finite magnetic field, resonances that strongly resemble Majorana bound states, including zero-bias pinning, become common to the point of ubiquity. Since Majorana bound states are predicted in only a limited parameter range in nanowire devices, we seek an alternative explanation for the observed zero-bias peaks. With the help of a self-consistent Poission-Schrödinger multiband model developed in parallel, we identify several families of trivial subgap states that overlap and interact, giving rise to a crowded spectrum near zero energy and zero-bias conductance peaks in experiments. These findings advance the search for Majorana bound states through improved understanding of broader phenomena found in superconductor-semiconductor systems.

Cognitive stimulation therapy (CST) for people with dementia--who benefits most?

BACKGROUND: The efficacy of cognitive stimulation therapy (CST) has been demonstrated, but little is known about the characteristics of people with dementia, which may predict a more positive response to CST. This study sought to investigate which factors may predict response to CST. METHODS: Two hundred and seventy-two participants with dementia took part in a 7-week CST intervention. Assessments were carried out pre-treatment and post-treatment. The results were compared with those of a previous comparable CST randomised control trial. A comparison of mean scores pre-CST and post-CST groups was undertaken, and contributing factors that predicted change in outcomes were examined. RESULTS: CST improved cognition and quality of life, and the results showed that the benefits of CST were independent of whether people were taking acetylcholinesteraseinhibitor (AChEI) medication. Increasing age was associated with cognitive benefits, as was female gender. Care home residents improved more than community residents on quality of life, but the community sample seemed to benefit more in relation to behaviour problems. CONCLUSIONS: These results demonstrate that CST improves cognition and quality of life for people with dementia including those already on AChEIs. Older age and being female were associated with increased cognitive benefits from the intervention. Consideration should be given to aspects of CST, which may enhance the benefits for people with dementia who are male and those younger than 80 years.

pH effects on molecular adsorption and solvation of p-nitrophenol at silica/aqueous interfaces.

Resonance-enhanced second-harmonic generation (SHG) was used to examine the effects of solution pH and surface charge on para-nitrophenol (pNP) adsorption to silica/aqueous interfaces. During the early stages of monolayer formation, SHG spectra of interfacial pNP showed a single resonant excitation wavelength at approximately 313 nm regardless of solution pH. This resonance wavelength of adsorbed species is lower than the 318 nm excitation maximum of pNP in bulk aqueous solution. Experiments were performed at pHs of 1.0, 5.0, 7.0, and 10.5. Under these conditions, the silica surface carried a surface charge that ranged from slightly positive (pH = 1) to strongly negative (pH = 10.5) due to protonation/deprotonation of surface silanol groups. Over the course of 1-3 h, SHG spectra of pNP evolved so that spectra from interfaces fully equilibrated with solution pH showed two clear resonance features with wavelengths of approximately 310 and 330 nm. These wavelengths imply that adsorbed pNP samples two discrete local solvation environments at the silica/aqueous interface. On the basis of the solvatochromic behavior of pNP in different bulk solvents, the shorter-wavelength feature corresponds to a local environment having an effective dielectric constant of 9.5 (similar to that of dichloromethane), while the longer-wavelength feature lies outside of pNP's standard solvatochromic window. This longer-wavelength result implies an effective dielectric constant greater than that of bulk water or an adsorption mechanism that has pNP adsorbates sharing a proton with surface silanol groups (and adopting an electronic structure that begins to resemble that of its deprotonated form, p-nitrophenoxide). The longer-wavelength feature is weakest in the low-pH systems when the surface is either neutral or slightly positively charged and most prominent at the negatively charged silica/aqueous (pH = 10.5) interface. pNP adsorption isotherms for all systems showed approximate Langmuir behavior. Using concentration-dependent data from both low and intermediate pH led to calculated adsorption energies of -19 ± 2 kJ/mol for all pH values except pH 10.5 where ΔG(ads) was -6 ± 2 kJ/mol. Taken together, these spectroscopic and adsorption studies of pNP adsorption to silica/aqueous interfaces as a function of aqueous pH show that interfacial acid/base chemistry can require hours to reach equilibrium and that the silica surface presents hydrogen-bonding solutes such as pNP with two distinct adsorption sites. The invariance of pNP's SHG spectra to bulk solution pH suggests that pNP solvation is dominated by substrate-solute interactions, with the adjacent solvent having very little influence on adsorbed solute properties.

Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

Guidelines for psychosocial interventions in dementia care: a European survey and comparison.

OBJECTIVE: The effectiveness of psychosocial interventions in treating people with dementia and their carers is increasingly emphasised in the literature. Dementia guidelines should summarise the scientific evidence and best practice that is currently available, therefore, it should include recommendations for psychosocial interventions. The aims of our study were (1) to collate dementia guidelines from countries across Europe and to check whether they included sections about psychosocial interventions, and (2) to compare the methodological quality and the recommendations for specific psychosocial interventions in these guidelines. METHODS: The European dementia guidelines were inventoried. The methodological quality of the guideline sections for psychosocial interventions was assessed with the (AGREE) Appraisal of Guidelines Research and Evaluation instrument. The recommendations for specific psychosocial interventions were extracted from each of these guidelines and compared. RESULTS: Guidelines for psychosocial interventions were found in five of 12 countries. Guideline developers, methodological quality and appreciation of available evidence influenced the inclusion of psychosocial interventions in dementia guidelines from Germany, Italy, the Netherlands, Spain and the UK. The UK NICE SCIE guideline had the best methodological quality and included the most recommendations for psychosocial interventions. Physical activity and carer interventions were recommended the most across all guidelines. CONCLUSION: The inclusion of psychosocial interventions in dementia guidelines is limited across Europe. High-quality guidelines that include psychosocial interventions and are kept up to date with the emerging evidence are needed. Throughout Europe, special attention to the implementation of evidence-based psychosocial care is needed in the next few years.

Perioperative considerations for the patient with asthma and bronchospasm.

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.

The prevalence of symptomatic posterior tibialis tendon dysfunction in women over the age of 40 in England.

BACKGROUND: To investigate the prevalence of posterior tibial tendon dysfunction (PTTD) in women over the age of 40. METHODS: A validated survey was posted to a random sample of 1000 women (over 40 years) from a GP group practice in Hertfordshire, England. Survey positive women were telephoned and when indicated, a detailed examination was performed. RESULTS: There were 582 usable responses. The majority indicated they had minor forefoot or no problems. Telephone contact was made with 116 women and of those 79 required examination. The diagnosis of symptomatic flatfeet was made in 9 patients, 7 patients had stage I PTTD, 12 patients had stage II PTTD and 9 patients had an adult acquired flatfoot deformity. CONCLUSIONS: This is the first report of the prevalence of stage I and II PTTD in women (over 40 years). The prevalence is 3.3% and all patients were undiagnosed despite characteristic and prolonged symptoms.

A Variable Neighbourhood Descent Heuristic for Conformational Search Using a Quantum Annealer.

Discovering the low-energy conformations of a molecule is of great interest to computational chemists, with applications in in silico materials design and drug discovery. In this paper, we propose a variable neighbourhood search heuristic for the conformational search problem. Using the structure of a molecule, neighbourhoods are chosen to allow for the efficient use of a binary quadratic optimizer for conformational search. The method is flexible with respect to the choice of molecular force field and the number of discretization levels in the search space, and can be further generalized to take advantage of higher-order binary polynomial optimizers. It is well-suited for the use of devices such as quantum annealers. After carefully defining neighbourhoods, the method easily adapts to the size and topology of these devices, allowing for seamless scaling alongside their future improvements.

WITHDRAWN: Reality orientation for dementia.

BACKGROUND: Reality Orientation (RO) was first described as a technique to improve the quality of life of confused elderly people, although its origins lie in an attempt to rehabilitate severely disturbed war veterans, not in geriatric work. It operates through the presentation of orientation information (eg time, place and person-related) which is thought to provide the person with a greater understanding of their surroundings, possibly resulting in an improved sense of control and self-esteem. There has been criticism of RO in clinical practice, with some fear that it has been applied in a mechanical fashion and has been insensitive to the needs of the individual. There is also a suggestion that constant relearning of material can actually contribute to mood and self-esteem problems. There is often little consistent application of psychological therapies in dementia services, so a systematic review of the available evidence is important in order to identify the effectiveness of the different therapies. Subsequently, guidelines for their use can be made on a sound evidence base. OBJECTIVES: To assess the evidence of effectiveness for the use of Reality Orientation (RO) as a classroom-based therapy on elderly persons with dementia. SEARCH STRATEGY: Computerised databases were searched independently by 2 reviewers entering the terms 'Reality Orientation, dementia, control, trial or study'. Relevant web sites were searched and some hand searching was conducted by the reviewer. Specialists in the field were approached for undocumented material, and all publications found were searched for additional references. SELECTION CRITERIA: All randomized controlled trials (RCTs), and all controlled trials with some degree of concealment, blinding or control for bias (second order evidence) of Reality Orientation as an intervention for dementia were included. The criteria for inclusion/exclusion involved systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. A measure of cognitive and/or behavioural change was needed. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined. MAIN RESULTS: 6 RCTs were entered in the analysis, with a total of 125 subjects (67 in experimental groups, 58 in control groups). Results were divided into 2 subsections: cognition and behaviour. Change in cognitive and behavioural outcomes showed a significant effect in favour of treatment. AUTHORS' CONCLUSIONS: There is some evidence that RO has benefits on both cognition and behaviour for dementia sufferers. Further research could examine which features of RO are particularly effective. It is unclear how far the benefits of RO extend after the end of treatment, but and it appears that a continued programme may be needed to sustain potential benefits.

Prevention of progression to cirrhosis in hepatitis C with fibrosis: effectiveness and cost effectiveness of sequential therapy with new direct-acting anti-virals.

BACKGROUND: The new direct-acting anti-virals (DAAs) for hepatitis C virus (HCV) infection offer higher cure rates, but at a much higher cost than the standard interferon-based treatments. AIM: To identify the cost-effective treatment for patients with HCV infection with F3 liver fibrosis who are at high risk of progression to cirrhosis. METHODS: A decision-analytic Markov model compared the health benefits and costs of all currently licensed treatments as single treatments and in sequential therapy of up to three lines. Costs were expressed in pound sterling from the perspective of the UK National Health Service. Health benefits were expressed in quality-adjusted life years. RESULTS: Treatment before progression to cirrhosis always offers the most health benefits for the least costs. Sequential therapy with multiple treatment lines cures over 89% of patients across all HCV genotypes while ensuring a cost-effective use of resources. Cost-effective regimes for HCV genotype 1 patients include first-line oral therapy with sofosbuvir-ledipasvir while peginterferon continues to have a role in other genotypes. CONCLUSIONS: The cost-effective treatment for HCV can be established using decision analytic modelling comparing single and sequential therapies. Sequential therapy with DAAs is effective and cost-effective in HCV patients with F3 fibrosis. This information is of significant benefit to health care providers with budget limitations and provides a sound scientific basis for drug treatment choices.

Neurologic abnormalities in schizophrenic patients and their families. I. Comparison of schizophrenic, bipolar, and substance abuse patients and normal controls.

The prevalence of neurologic abnormalities detectable on standard clinical examination by neurologists blind to diagnosis was compared for DSM-III-diagnosed, age- and sex-matched groups consisting of 24 schizophrenic (SCZ) patients, 24 patients with bipolar affective disorder (MDI) with history of psychosis, 24 patients hospitalized for alcohol or other drug abuse (D/A), and 24 normal volunteers (NL). The SCZ group had significantly more total abnormalities than the other three; both the MDI and D/A groups in turn had more total abnormalities than normal controls. After exclusion of findings due to medication or otherwise unrelated to the pathogenesis of psychiatric illness, only the SCZ-NL, SCZ-MDI, and D/A-NL differences remained significant. When neurologic abnormalities were further restricted to those indicating localized dysfunction of the corticospinal tracts, basal ganglia, or cerebellum, the only two persistent significant differences were between SCZ-NL and SCZ-MDI groups.

Neurologic abnormalities in schizophrenic patients and their families. II. Neurologic and psychiatric findings in relatives.

Neurologic abnormalities in 21 nonschizophrenic siblings and parents of schizophrenics, 24 DSM-III schizophrenics, and 24 normal "control" subjects were assessed by experienced neurologists blind to the subjects' psychiatric status. Medication artifacts and other neurologic signs likely to be etiologically irrelevant to psychiatric illness were excluded. Psychiatric diagnostic assessments of subjects were made blind to neurologic results. The prevalence of neurologic abnormalities in relatives was significantly greater than in controls, but similar to that among the schizophrenics. Relatives and controls differed even more markedly on signs involving motor system abnormalities of localizing significance. Finally, the relatives showed a suggestive dissociation of psychopathology and neurologic signs. The results appear most consistent with the hypothesis that overt schizophrenia may often result from the combined operation of two independent familial factors--one "psychopathologic," the other "neurologic".

Maprotiline treatment in depression. A perspective on seizures.

Eleven McLean Hospital (Belmont, Mass) depressed patients who experienced seizures while receiving maprotiline hydrochloride are presented, as are data on 87 cases reported to the manufacturer (Ciba-Geigy). Most seizures occurred at high dosages, sometimes after many weeks at a stable dose, but neither rapid dosage escalation nor high drug plasma levels seemed related to seizure occurrence. Our experience suggests that a long-acting metabolite might be responsible for seizures. Ten of the 11 McLean Hospital seizures occurred in patients receiving dosages outside of the since-revised current dosage guidelines, as did 60% of the seizures reported to the company. Data in this study suggest that reductions in maximum dosage of maprotiline prescribed after the initial six weeks of treatment could result in a further decrease in risk of seizures beyond that obtained from previous alterations in regimens.

Reminiscence therapy for dementia.

BACKGROUND: Reminiscence Therapy (RT) involves the discussion of past activities, events and experiences with another person or group of people, usually with the aid of tangible prompts such as photographs, household and other familiar items from the past, music and archive sound recordings. Reminiscence groups typically involve group meetings in which participants are encouraged to talk about past events at least once a week. Life review typically involves individual sessions, in which the person is guided chronologically through life experiences, encouraged to evaluate them, and may produce a life story book. Family care-givers are increasingly involved in reminiscence therapy. Reminiscence therapy is one of the most popular psychosocial interventions in dementia care, and is highly rated by staff and participants. There is some evidence to suggest it is effective in improving mood in older people without dementia. Its effects on mood, cognition and well-being in dementia are less well understood. OBJECTIVES: The objective of the review is to assess the effects of reminiscence therapy for older people with dementia and their care-givers. SEARCH STRATEGY: The trials were identified from a search of the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group on 4 May 2004 using the term "reminiscence". The CDCIG Specialized Register contains records from all major health care databases (MEDLINE, EMBASE, PsycLIT, CINAHL) and many ongoing trials databases and is regularly updated. We contacted specialists in the field and also searched relevant Internet sites. We hand-searched Aging and Mental Health, the Gerontologist, Journal of Gerontology, Current Opinion in Psychiatry, Current Research in Britain: Social Sciences, British Psychological Society conference proceedings and Reminiscence database. SELECTION CRITERIA: Randomised controlled trials and quasi-randomized trials of reminiscence therapy for dementia. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Five trials are included in the review, but only four trials with a total of 144 participants had extractable data. The results were statistically significant for cognition (at follow-up), mood (at follow-up) and on a measure of general behavioural function (at the end of the intervention period). The improvement on cognition was evident in comparison with both no treatment and social contact control conditions. Care-giver strain showed a significant decrease for care-givers participating in groups with their relative with dementia, and staff knowledge of group members' backgrounds improved significantly. No harmful effects were identified on the outcome measures reported. AUTHORS' CONCLUSIONS: Whilst four suitable randomized controlled trials looking at reminiscence therapy for dementia were found, several were very small studies, or were of relatively low quality, and each examined different types of reminiscence work. Although there are a number of promising indications, in view of the limited number and quality of studies, the variation in types of reminiscence work reported and the variation in results between studies, the review highlights the urgent need for more and better designed trials so that more robust conclusions may be drawn.

Blue toe syndrome. Causes and management.

The sudden development of cyanotic lesions on the feet may be a result of atheroembolic disease or a number of medical conditions. A careful history and physical examination, basic laboratory tests, and noninvasive vascular assessment usually distinguish between medical and surgical causes and direct the choice of further investigations. Specific therapy is often available for medical conditions causing this syndrome. The management of atheroembolic disease is more controversial. In particular, further research is necessary to determine which patients need surgical intervention and which patients can be managed safely by medical therapy.

Changing concepts in surgical management of renovascular hypertension.

As newer surgical techniques and concepts have emerged, including revascularization of the totally occluded renal artery and alternatives to aortorenal bypass (hepatic, splenic, or iliac artery to renal artery grafts), our patient population has changed. Patients with diffuse atherosclerotic disease, bilateral renal artery stenosis, totally occluded renal arteries, and azotemia are being referred for renal revascularization, thereby changing the indications for operation and the results that can be anticipated. Although our results in patients operated on solely for uncontrollable hypertension or renal failure have been successful, much work needs to be done to improve the results obtained when patients have a combination of uncontrollable hypertension and renal failure.

Individual patient data network meta-analysis of mortality effects of implantable cardiac devices.

OBJECTIVE: Implantable cardioverter defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and the combination therapy (CRT-D) have been shown to reduce all-cause mortality compared with medical therapy alone in patients with heart failure and reduced EF. Our aim was to synthesise data from major randomised controlled trials to estimate the comparative mortality effects of these devices and how these vary according to patients' characteristics. METHODS: Data from 13 randomised trials (12 638 patients) were provided by medical technology companies. Individual patient data were synthesised using network meta-analysis. RESULTS: Unadjusted analyses found CRT-D to be the most effective treatment (reduction in rate of death vs medical therapy: 42% (95% credible interval: 32-50%), followed by ICD (29% (20-37%)) and CRT-P (28% (15-40%)). CRT-D reduced mortality compared with CRT-P (19% (1-33%)) and ICD (18% (7-28%)). QRS duration, left bundle branch block (LBBB) morphology, age and gender were included as predictors of benefit in the final adjusted model. In this model, CRT-D reduced mortality in all subgroups (range: 53% (34-66%) to 28% (-1% to 49%)). Patients with QRS duration ≥150 ms, LBBB morphology and female gender benefited more from CRT-P and CRT-D. Men and those <60 years benefited more from ICD. CONCLUSIONS: These data provide estimates for the mortality benefits of device therapy conditional upon multiple patient characteristics. They can be used to estimate an individual patient's expected relative benefit and thus inform shared decision making. Clinical guidelines should discuss age and gender as predictors of device benefits.

Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors.

We compared the efficacy of ponatinib and second-generation tyrosine kinase inhibitors (2G-TKIs: bosutinib, dasatinib, and nilotinib) in chronic phase CML resistant/intolerant to ≥1 prior 2G-TKI. Estimated probabilities of CCyR with 2G-TKI ranged from 22% to 26%, compared with 60% (95% CrI 52-68%) with ponatinib. The estimated probability of ponatinib providing higher response rate than all other included treatments was 99% (CCyR) and 97% (MCyR). Use of further 2G-TKI may provide limited benefit in CP-CML patients resistant/intolerant to prior 2G-TKI treatment. Compared with 2G-TKIs, ponatinib is estimated to provide substantially higher probability of achieving CCyR and MCyR; safety was not compared.