Lower Bounds on the Noiseless Worst-Case Complexity of Efficient Global Optimization.

Efficient global optimization is a widely used method for optimizing expensive black-box functions. In this paper, we study the worst-case oracle complexity of the efficient global optimization problem. In contrast to existing kernel-specific results, we derive a unified lower bound for the oracle complexity of efficient global optimization in terms of the metric entropy of a ball in its corresponding reproducing kernel Hilbert space. Moreover, we show that this lower bound nearly matches the upper bound attained by non-adaptive search algorithms, for the commonly used squared exponential kernel and the Matérn kernel with a large smoothness parameter ν. This matching is up to a replacement of d/2 by d and a logarithmic term logRϵ, where d is the dimension of input space, R is the upper bound for the norm of the unknown black-box function, and ϵ is the desired accuracy. That is to say, our lower bound is nearly optimal for these kernels.

Refining ambulance clinical response models: The impact on ambulance response and emergency department presentations.

OBJECTIVE: The ambulance service in Victoria, Australia implemented a revised clinical response model (CRM) in 2016 which was designed to increase the diversion of low-acuity Triple Zero (000) calls to secondary telephone triage and reduce emergency ambulance dispatches. The present study evaluates the influence of the revised CRM on emergency ambulance response times and ED presentations. METHODS: A retrospective study of emergency calls for ambulance between 1 January 2015 and 31 December 2018. Ambulance data were linked with ED presentations occurring up to 48 h after contact. Interrupted time series analyses were used to evaluate the impact of the revised CRM. RESULTS: A total of 2 365 529 calls were included. The proportion allocated a Code 1 (time-critical, lights/sirens) dispatch decreased from 56.6 to 41.0% after implementation of the revised CRM. The proportion of calls not receiving an emergency ambulance increased from 10.4 to 19.6%. Interrupted time series analyses demonstrated an improvement in Code 1 cases attended within 15 min (Key Performance Indicator). However, for patients with out-of-hospital cardiac arrest or requiring lights and sirens transport to hospital, there was no improvement in response time performance. By the end of the study period, there was also no difference in the proportion of callers presenting to ED when compared with the estimated proportion assuming the revised CRM had not been implemented. CONCLUSION: The revised CRM was associated with improved Code 1 response time performance. However, there was no improvement in response times for high acuity patients, and no change in the proportion of callers presenting to ED.

The Dragonflies and Damselflies (Insecta: Odonata) of Canada: species list, geographical distribution, status, and conservation ranks.

As of August 2023, 220 species in 57 genera and 10 families of damselflies and dragonflies (Insecta: Odonata) are recorded for Canada. Since the publication of the first edition in 2005, 14 species have been added to the list; one,Neurocordulia obsoleta (Say) has been removed because of a misidentification and another, Sympetrum occidentale, has been to synonymy. Conservation ranks are given for species in all 13 provinces and territories. English and French names for all listed species are included. Literature sources are discussed and presented, as is information on species status and the addition and exclusion of species. Sections on taxonomy and variation, subspecies, presumed hybrids, the introduction of exotic species, notable range extensions and observations, and conservation and protection are also provided.

Is diabetic retinopathy screening worthwhile among people first diagnosed with diabetes at older ages? A cohort study of Norfolk diabetic retinopathy screening programme.

AIMS: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. METHODS: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. RESULTS: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70-79 and £26,214 in those aged 80-89. CONCLUSIONS: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable.

Frequency of visual involvement in a 10-year interdisciplinary cohort of patients with giant cell arteritis.

BACKGROUND: We present the largest study of the frequency and nature of visual complications in a cohort of 350 patients consecutively diagnosed with giant cell arteritis (GCA). METHODS: All individuals were assessed using structured forms and diagnosed using imaging or biopsy. A binary logistic regression model was used to analyse data for predicting visual loss. RESULTS: Visual symptoms occurred in 101 (28.9%) patients, with visual loss in one or both eyes in 48 (13.7%) patients. Four patients had binocular visual loss. Anterior ischaemic optic neuropathy (N=31), retinal artery obstruction (N=8) and occipital stroke (N=2) were the main causes of visual loss. Of the 47 individuals who had repeat visual acuity testing at 7 days, three individuals had improvement to 6/9 or better. After introducing the fast-track pathway, the frequency of visual loss decreased from 18.7% to 11.5%. Age at diagnosis (odds ratio (OR) 1.12) and headache (OR 0.22) were significant determinants of visual loss in a multivariate model. Jaw claudication trended to significance (OR 1.96, p=0.054). CONCLUSIONS: We recorded a visual loss frequency of 13.7% in the largest cohort of patients with GCA examined from a single centre. Although improvement in vision was rare, a dedicated fast-track pathway reduced visual loss. Headache could result in earlier diagnosis and protect against visual loss.

Palliative care teaching in the new internal medicine curriculum: Project ECHO-an innovative approach to postgraduate education.

BACKGROUND: The Internal Medicine Training (IMT) Programme is an evolution of Core Medical Training introduced in 2019. The IMT curriculum places an increased emphasis on palliative care; however, access to palliative care training is variable. Project ECHO (Extension of Community Healthcare Outcomes) develops communities of practice and is a valuable tool for medical education. We report on an evaluation of Project ECHO to deliver palliative medicine training across a geographically large deanery in the North of England. METHODS: The Project ECHO training programme involved multipoint video technology, telementoring, expert talks and case-based discussions over six sessions, and was fully mapped to the palliative care component of the IMT curriculum. We collected data particularly around attendance and self-reported confidence and knowledge. RESULTS: By creating a community of practice, we provided virtual placements and over 9 hours of virtual direct contact with palliative medicine consultants; and in total, 921 individual attendances occurred, with 62% attending all six sessions. The course was associated with an increase in self-reported confidence and high satisfaction. DISCUSSION: Project ECHO is an effective method of delivering teaching to trainees across a large geographical area. Course evaluation shows outstanding results in trainee satisfaction, confidence, knowledge, patient care, clinical skills and reduction in fear when managing death and dying.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

COVID-19-associated mixed cilioretinal artery occlusion and central venous occlusion in a fit and healthy young patient.

Retinal artery occlusion is an unusual phenomenon in younger patients without background of diseases leading to hypercoagulable states. COVID-19 infection is increasingly recognised as being associated with thrombotic conditions. We present a case of a young female who is otherwise fit and well apart from recent COVID-19 infection, who presented with a mixed cilioretinal artery and venous occlusion.

Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy.

Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR. Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay. Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c. Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.

OBJECTIVES: Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. METHODS: We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. RESULTS: All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. CONCLUSIONS: Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.

Improving the quality of care for people with giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis with numerous potential complications and societal costs. After the publication of international guidelines, we found a number of deficiencies in the local care pathway of patients suspected to have GCA. These included poor referral and management pathways, and absence of dedicated monitoring and follow-up. In this paper, we describe a 10-year transformation which led to our service being nominated for a national award.A comprehensive consensus pathway saw referral numbers rise from 19 to 135 from 2012 to 2019. A consensus management pathway has meant that patients are assessed within 2 days of referral and glucocorticoids started at point of referral. All patients with suspected GCA are clerked and managed according to this agreed pathway which is available on the hospital intranet. The introduction of diagnostic ultrasonography has meant that the need for biopsies has dropped by >80% reducing the annual cost of diagnostics by >£140,000. The introduction of a vasculitis specialist nurse has resulted in improving education, contact and speed of access to our service. The improvements in the service resulted in our service becoming a finalist in the Royal College of Physicians Excellence in Patient Care Award in 2020.

Coronavirus disease 2019 (COVID-19) and psychological distress in China: Does neighbourhood matter?

Using individual data (n = 937) obtained from an online questionnaire between 20th January and 13th February, the early stage of the outbreak of the Coronavirus Disease 2019 (COVID-19) in 2020, we explore the direct association between people's perceptions of Coronavirus Disease 2019 (COVID-19) and psychological distress. We further examine the moderating role of neighbourhood environment and this distress. We find that people living in infected communities tend to perceive higher level of psychological distress compared to people living in uninfected communities. People's expected duration of COVID-19 is associated with higher psychological distress and this is partially moderated by the perception of neighbourhood noise level and overall environment quality. Additional results quantify the evidence that a quiet and well maintained neighbourhood environment could reduce the negative influences of expectation of a long duration of COVID-19 on people's psychological distress.

U.K. Community Earth System Modeling for CMIP6.

We describe the approach taken to develop the United Kingdom's first community Earth system model, UKESM1. This is a joint effort involving the Met Office and the Natural Environment Research Council (NERC), representing the U.K. academic community. We document our model development procedure and the subsequent U.K. submission to CMIP6, based on a traceable hierarchy of coupled physical and Earth system models. UKESM1 builds on the well-established, world-leading HadGEM models of the physical climate system and incorporates cutting-edge new representations of aerosols, atmospheric chemistry, terrestrial carbon, and nitrogen cycles and an advanced model of ocean biogeochemistry. A high-level metric of overall performance shows that both models, HadGEM3-GC3.1 and UKESM1, perform better than most other CMIP6 models so far submitted for a broad range of variables. We point to much more extensive evaluation performed in other papers in this special issue. The merits of not using any forced climate change simulations within our model development process are discussed. First results from HadGEM3-GC3.1 and UKESM1 include the emergent climate sensitivity (5.5 and 5.4 K, respectively) which is high relative to the current range of CMIP5 models. The role of cloud microphysics and cloud-aerosol interactions in driving the climate sensitivity, and the systematic approach taken to understand this role, is highlighted in other papers in this special issue. We place our findings within the broader modeling landscape indicating how our understanding of key processes driving higher sensitivity in the two U.K. models seems to align with results from a number of other CMIP6 models.

The relationship between glycated haemoglobin levels and the risk of giant cell arteritis - a case-control study.

OBJECTIVES: The EULAR core dataset for observational studies in GCA does not include glycated haemoglobin (HbA1c). A multivariable score to stratify the pre-test probability of GCA also does not include HbA1c. There have been contradictory reports about diabetes mellitus being a risk factor for GCA. We report the first study analysing the relationship of pre-diagnosis HbA1c with the risk of GCA. METHODS: This was a single-centre retrospective case-control study conducted in Norfolk, UK. All GCA cases were diagnosed with imaging or biopsy. Each case was assigned two age- and sex-matched controls. The primary outcome measure was the glycaemic status (HbA1c categorized into euglycaemia, pre-diabetes or diabetes mellitus) at diagnosis between cases and controls. The HbA1c was compared between two groups using the Mann-Whitney U test. The glycaemic categorization was compared using the χ2 test. RESULTS: One hundred and twelve cases and 224 controls were included. The median (interquartile range) of HbA1c of cases and controls was 40 (37, 43) and 41 (39, 47) mmol/mol (P < 0.001), respectively. Ten of 112 cases and 52 of 224 controls had diabetes mellitus. The χ2 test demonstrated a significant interaction between glycaemic state and GCA (P = 0.006). Individuals with diabetes mellitus had an odds ratio (95% CI) of 0.32 (0.13, 0.74) (P = 0.008) of having GCA compared with euglycaemic individuals. CONCLUSION: HbA1c in the diabetic range reduces the probability of GCA. HbA1c should be considered in any multivariable score to calculate the risk of GCA, and in future development of diagnostic and classification criteria. There is a need for an epidemiological study looking at the possibility of a protective nature of diabetes mellitus against GCA or whether it is only a mimic.

A field comparison of marine mammal detections via visual, acoustic, and infrared (IR) imaging methods offshore Atlantic Canada.

Impulsive sounds generated during seismic surveys have elicited behavioral responses in marine mammals and could cause hearing impairment or injury. Mitigating exposure to seismic sound often relies on real-time marine mammal detection. Detection performance is influenced by detection method, environmental conditions, and observer experience. We conducted a field comparison of real-time detections made by marine mammal observers (MMOs), a rotating infrared (IR) camera, and via passive acoustic monitoring (PAM). Data were collected from a 38 m research vessel offshore Atlantic Canada. Our results indicate that overall detection rates increase when complementary methods are used. MMOs and PAM are likely the most effective combination during high seas and precipitation. PAM and IR can be used in darkness. In good visibility, MMOs with IR or PAM should increase detections. Our results illustrate the importance of addressing false positive IR detections, matching system capabilities to sea conditions/species of interest, and employing experienced observers.

An exploration of the attitudes and perceptions of the UK public towards self-care for minor ailments.

AIMS AND OBJECTIVES: the purpose of this pilot study was to explore the attitudes and perceptions of members of the UK public towards self-care for minor ailments. BACKGROUND: with an ageing and increasing population, and an NHS under extreme pressure, methods to reduce demand on health services are vital. Increasing the use of self-care for minor ailments is one way in which this pressure could be alleviated. DESIGN AND METHOD: this study used qualitative methods including semi-structured telephone interviews. The data were then evaluated, and key themes drawn out using thematic analysis. FINDINGS: the results showed that the public are aware of the notion of self-care, and some are engaging with it. However, for a number of reasons, patients are still likely to want a face-to-face appointment despite the use of online and telephone advice services. CONCLUSION: the study highlighted that there are multifactorial aspects impacting on a patient's likelihood of engaging in self-care when faced with a minor illness. The results are not generalisable to every member of the public, but interesting questions are raised with regard to the usefulness of current public health messages in various media when there appears to be a lack of desire from the public to use some recommended services.

Validating a diagnostic GCA ultrasonography service against temporal artery biopsy and long-term clinical outcomes.

Currently, there is no mechanism for service validation of diagnostic ultrasonography (US) for giant cell arteritis (GCA). Temporal artery biopsy (TAB) and classification criteria are poor benchmarks. We validated our service against physician-verified diagnosis at 100 weeks (100wD). Twenty-five patients underwent US within 7 days, and TAB within 28 days, of commencing prednisolone. US, TAB and baseline diagnosis (bD) were all compared with 100wD using Cohen's kappa. Fourteen US and 8 TABs were positive. Twenty at baseline and 14 at 100 weeks had diagnosis of GCA. The kappa (95% CI) were 0.4 (0.1, 0.7) for US vs. TAB; 0.5 (0.2, 0.8) for US vs. bD and 0.2 (0.0, 0.4) for TAB vs. bD. Versus 100wD, the kappa (95% CI) were 0.8 (0.6, 1.0) for US; 0.4 (0.1, 0.7) for TAB and 0.6 (0.3, 0.9) for bD. Seven cases were US+/TAB-. Four had alternate confirmation: 18FDG-PET (n = 1), CT Aorta (n = 1) and US at relapse (n = 2). At 100 weeks, 4 cases (all US-/TAB-) with bD of GCA had alternative diagnoses including cancer (n = 2). This is the first study validating US service provision for GCA. Twenty-five US with a robust kappa on comparison with long-term diagnosis validates our service. A diagnosis of GCA should be made with extreme caution for US-/TAB- cases.Key Points• This is the first study offering a way to validate a new diagnostic US service by validation against TAB and long-term physician-verified diagnosis.• US has substantial to near-perfect agreement with long-term physician-verified diagnosis and is more reliable than TAB in our hands.• Alternative diagnoses should be sought in patients with dual negativity for US and TAB.

Does Residents' Satisfaction with the Neighbourhood Environment Relate to Residents' Self-Rated Health? Evidence from Beijing.

OBJECTIVE: The aim of this study is to examine the association between satisfaction with two types of green space and residents' self-rated health by comparing neighbourhood green space (NGS) and community green space (CGS) across spatial dimensions. METHOD: This study was based on 4291 workers from a large-scale individual survey of inhabitants of Beijing city in 2013. Multilevel ordered logistic regression analysis was used to examine the associations between residents' satisfaction with the two types of green spaces and residents' self-rated health. RESULTS: Residents who are more satisfied with NGS and CGS have higher odds of reporting good self-rated health outcomes. Such effects are more pronounced for residents living close to NGS and tend to decline non-linearly over space. CONCLUSION: Additional results quantify the differentiated effects on self-rated health between urban and suburban residents. The findings of this study suggest that the effects of residents' satisfaction with different types of green space on health benefits should be taken into account in the land-use design of green space preservation and development policies.