Indocyanine Green Is a Safe and Effective Alternative to Radioisotope in Breast Cancer Sentinel Lymph Node Biopsy regardless of Patient Body Mass Index.

INTRODUCTION: A recent meta-analysis [Lancet Oncol. 2010;11:908-909] has confirmed high sensitivity of indocyanine green (ICG) fluorescence mapping for sentinel node detection in early breast cancer. Concerns have previously been raised regarding the efficacy in patients with high body mass index (BMI). MATERIALS AND METHODS: All consecutive patients undergoing sentinel lymph node biopsies (SLNBs) for early breast cancer in NHS Tayside were included in a prospective audit of surgical and pathology findings. All patients included in the study received dual injection of patent blue dye and ICG. Approval was obtained from the local Caldicott guardian for collection and use of personal data. RESULTS: Of 239 cases, all were female patients of mean age 62 years (range 27-93). In 4.2% (10/239) of cases, neither blue dye nor ICG was present in the axilla. Of the remaining 229 SLNB cases in this series, surgeons documented retrieval of 451 nodes, with a mean surgical nodal count per case of 1.97 (range 1-5) and pathological nodal count of 2.15 (range 0-7). Eighty three cases were performed in patients with BMI 30-39.9 and 21 cases with BMI ≥40, with nodal detection rates of 96.4% (80/83) and 95.2% (20/21), respectively, in these groups of patients. Twenty percent (48/229) of cases had nodal metastases on histopathology. CONCLUSIONS: This is a large single-center study which demonstrates the safety and accuracy of the combined ICG and blue dye technique for SLNB in breast cancer. This is represented by nodal detection rates and node positivity rates which are comparable to previous multicenter studies of standard SLNB regardless of BMI.

Catalytic Enantioselective 6π Photocyclization of Acrylanilides.

Controlling absolute stereochemistry in catalytic photochemical reactions is generally challenging owing to high rates of background reactivity. Successful strategies broadly rely on selective excitation of the reaction substrate when associated with a chiral catalyst. Recent studies have demonstrated that chiral Lewis acid complexes can enable selective energy transfer from a photosensitizer to facilitate enantioselective triplet state reactions. Here, we apply this approach to the enantioselective catalysis of a 6π photocyclization through the design of an iridium photosensitizer optimized to undergo energy transfer to a reaction substrate only in the presence of a chiral Lewis acid complex. Among a group of iridium(III) sensitizers, enantioselectivity and yield closely correlate with photocatalyst triplet energy within a narrow window enabled by a modest reduction in substrate triplet energy upon binding a scandium/ligand complex. These results demonstrate that photocatalyst tuning offers a means to suppress background reactivity and improve enantioselectivity in photochemical reactions.

NHS funding for dental undergraduate human disease teaching in the UK: a 20-year review.

Introduction This study identifies funding of NHS services supporting dental students' teaching over the last 20 years, focusing on human disease (HD) teaching.Aims To identify NHS funding for education in UK dental schools following publication of the 1997 General Dental Council curriculum introducing specific funding for HD teaching and the years 2015/16 to 2019/20.Material and methods Searches of the medical literature, grey literature (government and regulatory authority reports, legislative articles) and freedom of information requests to hospitals helping to deliver teaching.Results There are few publications describing current funding of dental undergraduate teaching. Freedom of information requests gave data for NHS hospital allocations for teaching both clinical dentistry and HD. HD funding has dropped by £2 million in five years.Conclusions NHS Trusts linked to dental schools receive monies to deliver teaching and offset costs of accommodating students. Tracking these funds over 20 years has seen some schools lose up to £1 million of HD funding and some lose it all. Greater transparency regarding funding for HD delivery would help improve teaching. Increasing numbers of older patients, with a greater chronic disease burden who are retaining teeth into later life, need graduating dentists with good medical knowledge to deliver safe care.

Economic estimation of Bitcoin mining's climate damages demonstrates closer resemblance to digital crude than digital gold.

This paper provides economic estimates of the energy-related climate damages of mining Bitcoin (BTC), the dominant proof-of-work cryptocurrency. We provide three sustainability criteria for signaling when the climate damages may be unsustainable. BTC mining fails all three. We find that for 2016-2021: (i) per coin climate damages from BTC were increasing, rather than decreasing with industry maturation; (ii) during certain time periods, BTC climate damages exceed the price of each coin created; (iii) on average, each $1 in BTC market value created was responsible for $0.35 in global climate damages, which as a share of market value is in the range between beef production and crude oil burned as gasoline, and an order-of-magnitude higher than wind and solar power. Taken together, these results represent a set of sustainability red flags. While proponents have offered BTC as representing "digital gold," from a climate damages perspective it operates more like "digital crude".

Shrinking lakes, air pollution, and human health: Evidence from California's Salton Sea.

Due to increased water withdrawals and ongoing climate change, many inland lakes around the world are shrinking and dry lake beds can be significant sources of particulate matter air pollution. Using a natural experiment provided by the shrinking Salton Sea in California, this paper shows that each one-foot drop in lake elevation is associated with a 0.28 µg/m3 (2.6%) increase in PM2.5 concentrations. IV model results then show that Salton Sea-induced changes in PM2.5 over 1998-2014 led to increases in respiratory mortality of 1.4/yr.-15.6/yr. in the counties surrounding the lake, generating $13.2-$147.3 million in annual health costs.

Practical and Scalable Kinetic Resolution of BINOLs Mediated by a Chiral Counterion.

BINOLs are valuable and widely used building blocks, chiral ligands, and catalysts that are effective across a remarkable range of different chemical transformations. Here we demonstrate that an ammonium salt catalyzed kinetic resolution of racemic BINOLs with benzyl tosylate proceeds with s up to 46. This is a scalable and practical process that can be applied across >30 different C2 - and non-C2 -symmetric BINOLs. Implementation of this method enables the enantioselective synthesis of a wide range of BINOL derivatives with over 99:1 e.r.

Application of an Original Wildfire Smoke Health Cost Benefits Transfer Protocol to the Western US, 2005-2015.

Recent growth in the frequency and severity of US wildfires has led to more wildfire smoke and increased public exposure to harmful air pollutants. Populations exposed to wildfire smoke experience a variety of negative health impacts, imposing economic costs on society. However, few estimates of smoke health costs exist and none for the entire Western US, in particular, which experiences some of the largest and most intense wildfires in the US. The lack of cost estimates is troublesome because smoke health impacts are an important consideration of the overall costs of wildfire. To address this gap, this study provides the first time series estimates of PM2.5 smoke costs across mortality and several morbidity measures for the Western US over 2005-2015. This time period includes smoke from several megafires and includes years of record-breaking acres burned. Smoke costs are estimated using a benefits transfer protocol developed for contexts when original health data are not available. The novelty of our protocol is that it synthesizes the literature on choices faced by researchers when conducting a smoke cost benefit transfer. On average, wildfire smoke in the Western US creates $165 million in annual morbidity and mortality health costs.

Broadband classification and statistics of echoes from aggregations of fish measured by long-range, mid-frequency sonar.

For horizontal-looking sonar systems operating at mid-frequencies (1-10 kHz), scattering by fish with resonant gas-filled swimbladders can dominate seafloor and surface reverberation at long-ranges (i.e., distances much greater than the water depth). This source of scattering, which can be difficult to distinguish from other sources of scattering in the water column or at the boundaries, can add spatio-temporal variability to an already complex acoustic record. Sparsely distributed, spatially compact fish aggregations were measured in the Gulf of Maine using a long-range broadband sonar with continuous spectral coverage from 1.5 to 5 kHz. Observed echoes, that are at least 15 decibels above background levels in the horizontal-looking sonar data, are classified spectrally by the resonance features as due to swimbladder-bearing fish. Contemporaneous multi-frequency echosounder measurements (18, 38, and 120 kHz) and net samples are used in conjunction with physics-based acoustic models to validate this approach. Furthermore, the fish aggregations are statistically characterized in the long-range data by highly non-Rayleigh distributions of the echo magnitudes. These distributions are accurately predicted by a computationally efficient, physics-based model. The model accounts for beam-pattern and waveguide effects as well as the scattering response of aggregations of fish.

The social costs of uranium mining in the US Colorado Plateau cohort, 1960-2005.

OBJECTIVES: Long-term social costs associated with underground uranium mining are largely unknown. This study estimated health costs of Native American and white (Hispanic and non-Hispanic origin) uranium miners in the US Public Health Service Colorado Plateau cohort study. METHODS: Elevated uranium miner person-years of life lost (PYLL) were calculated from the most recent study of the Colorado Plateau cohort over 1960-2005. Nine causes of death categories were included. Costs to society of miner PYLL were monetized using the value of a statistical life-year approach. RESULTS: Costs over 1960-2005 totaled $2 billion USD [95% CI: $1.8, $2.2], or $2.9 million per elevated miner death. This corresponds to $43.1 million [95%: $38.7, $48.7] in annual costs. Lung cancer was the most costly cause of death at $1.4 billion [95%: $1.3, $1.5]. Absolute health costs were largest for white miners, but Native Americans had larger costs per elevated death. Annual excess mortality over 1960-2005 averaged 366.4 per 100,000 miners; 404.6 (white) and 201.5 per 100,000 (Native American). CONCLUSIONS: This research advances our understanding of uranium extraction legacy impacts, particularly among indigenous populations.

PLAN or get SLAM'ed: Optimal management of invasive species in the presence of indirect health externalities.

This paper examines invasive species management when invasive species impact health outcomes indirectly through changes to environmental quality. For example, the emerald ash borer (EAB) has destroyed millions of ash trees throughout North America and has the potential to impact rates of cardiorespiratory mortality and morbidity through ash trees' ability to capture airborne pollutants. Optimal management inclusive of indirect health externalities may be different than status quo plans because the links between nature and health are complex, dynamic, and spatially heterogeneous. We produce a novel dynamic bioeconomic-health model to determine optimal EAB management in the face of such health effects. Our results show that including health increases net benefits of management substantially and that a "one size fits all" management approach is suboptimal given forest cover and demographic spatial heterogeneity. Net benefits to society are 873% higher and air pollution related mortality incidence is 82% lower when health externalities are included in management profiles using insecticide treatments and non-ash tree preemptive plantings without removal. Additionally, constrained managers optimally substitute toward preemptive tree plantings and away from insecticide use in the presence of indirect health externalities as a way to minimize disruptions to air quality. This paper has policy implications for the optimal management of environmental amenities.

Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab.

Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies.

What are the health costs of uranium mining? A case study of miners in Grants, New Mexico.

BACKGROUND: Uranium mining is associated with lung cancer and other health problems among miners. Health impacts are related with miner exposure to radon gas progeny. OBJECTIVES: This study estimates the health costs of excess lung cancer mortality among uranium miners in the largest uranium-producing district in the USA, centered in Grants, New Mexico. METHODS: Lung cancer mortality rates on miners were used to estimate excess mortality and years of life lost (YLL) among the miner population in Grants from 1955 to 2005. A cost analysis was performed to estimate direct (medical) and indirect (premature mortality) health costs. RESULTS: Total health costs ranged from $2·2 million to $7·7 million per excess death. This amounts to between $22·4 million and $165·8 million in annual health costs over the 1955-1990 mining period. Annual exposure-related lung cancer mortality was estimated at 2185·4 miners per 100 000, with a range of 1419·8-2974·3 per 100 000. CONCLUSIONS: Given renewed interest in uranium worldwide, results suggest a re-evaluation of radon exposure standards and inclusion of miner long-term health into mining planning decisions.

Echo statistics of individual and aggregations of scatterers in the water column of a random, oceanic waveguide.

The relative contributions of various physical factors to producing non-Rayleigh distributions of echo magnitudes in a waveguide are examined. Factors that are considered include (1) a stochastic, range-dependent sound-speed profile, (2) a directional acoustic source, (3) a variable scattering response, and (4) an extended scattering volume. A two-way parabolic equation model, coupled with a stochastic internal wave model, produces realistic simulations of acoustic propagation through a complex oceanic sound speed field. Simulations are conducted for a single frequency (3 kHz), monostatic sonar with a narrow beam (5° -3 dB beam width). The randomization of the waveguide, range of propagation, directionality of the sonar, and spatial extent of the scatterers each contribute to the degree to which the echo statistics are non-Rayleigh. Of critical importance are the deterministic and stochastic processes that induce multipath and drive the one-way acoustic pressure field to saturation (i.e., complex-Gaussian statistics). In this limit predictable statistics of echo envelopes are obtained at all ranges. A computationally low-budget phasor summation can successfully predict the probability density functions when the beam pattern and number of scatterers ensonified are known quantities.

Use of the distorted wave born approximation to predict scattering by inhomogeneous objects: application to squid.

A new method has been developed to predict acoustic scattering by weakly scattering objects with three-dimensional variability in sound speed and density. This variability can take the form of inhomogeneities within the body of the scatterer and/or geometries where the acoustic wave passes through part of the scattering body, into the surrounding medium, and back into the body. This method applies the distorted wave Born approximation (DWBA) using a numerical approach that rigorously accounts for the phase changes within a scattering volume. Ranges of validity with respect to material properties and numerical considerations are first explored through comparisons with modal-series-based predictions of scattering by fluid-filled spherical and cylindrical fluid shells. The method is then applied to squid and incorporates high resolution spiral computerized tomography (SCT) scans of the complex morphology of the organism. Target strength predictions based on the SCT scans are compared with published backscattering data from live, freely swimming and tethered squid. The new method shows significant improvement for both single-orientation and orientation-averaged scattering predictions over the DWBA-homogeneous-prolate-spheroid model.

Classification of broadband echoes from prey of a foraging Blainville's beaked whale.

Blainville's beaked whales (Mesoplodon densirostris) use broadband, ultrasonic echolocation signals with a -10 dB bandwidth from 26 to 51 kHz to search for, localize, and approach prey that generally consist of mid-water and deep-water fishes and squid. Although it is well known that the spectral characteristics of broadband echoes from marine organisms vary as a function of size, shape, orientation, and anatomical group, there is little evidence as to whether or not free-ranging toothed whales use spectral cues in discriminating between prey and nonprey. In order to study the prey-classification process, a stereo acoustic tag was deployed on a Blainville's beaked whale so that emitted clicks and the corresponding echoes from targets in the water could be recorded. A comparison of echoes from targets apparently selected by the whale and those from a sample of scatterers that were not selected suggests that spectral features of the echoes, target strengths, or both may have been used by the whale to discriminate between echoes. Specifically, the whale appears to favor targets with one or more nulls in the echo spectra and to seek prey with higher target strengths at deeper depths.

Sex and age differences in coping styles among children with chronic pain.

The purpose of this study was to examine sex and age differences in coping strategies among pediatric patients with chronic pain. Sex differences are reported in the adult pain and coping literatures, but little attention has been given to possible distinctions in coping styles in the pediatric chronic pain population. Investigating pain coping skills at an early age may provide clinicians with a better understanding of the evolution of characteristic coping styles and identify areas for intervention. Pain intensity (Visual Analog Scale), pain coping strategies (Pain Coping Questionnaire), and coping efficacy were assessed in children (ages 8-12 years) and adolescents (ages 13-18 years), presenting to a pediatric chronic pain clinic (n=272). Significant sex differences in coping strategies were found. After controlling for pain intensity, girls used social support seeking more than boys, while boys used more behavioral distraction techniques. Adolescents engaged in more positive self-statements (a cognitive strategy) than children. Both boys and girls showed a trend toward pain coping efficacy being negatively correlated with average pain intensity. For girls, pain coping efficacy was also significantly negatively correlated with internalizing/catastrophizing. However, no sex or age differences in coping efficacy were found. This study demonstrates the early emergence of sex- and aged-based preferences in coping strategies among children and adolescents with chronic pain. The findings establish a basis for further research on early social influences in the development of pain coping styles in males and females. Implications for further clinical research in this area are discussed.

Psychosocial risks for disability in children with chronic back pain.

UNLABELLED: Psychosocial factors related to disability in adults with chronic back pain have been well studied, but little is known about factors associated with functional impairment in pediatric patients with chronic back pain. The purpose of this study was to examine whether 2 potential risk factors-use of catastrophizing as a coping technique and presence of a familial pain history-were associated with disability in pediatric back pain patients. Participants were 65 patients (ages 8-18) with chronic back pain seen at a multidisciplinary pain clinic. Patients completed measures of pain (visual analog scales), disability (Functional Disability Inventory), and catastrophizing (Internalizing/Catastrophizing subscale of the Pain Coping Questionnaire). Parents provided demographic information and familial pain history. Patients reported that chronic back pain caused disruptions in their daily functioning and they missed, on average, 2.5 days of school every month. Catastrophizing and familial chronic pain history both were significantly associated with greater disability, with use of catastrophizing being the stronger predictor of disability. This study presents important findings on potential psychosocial risk factors of functional disability in children and adolescents with chronic back pain. Future research might clarify mechanisms by which such coping styles are developed and explore how familial communication about pain might influence a child's coping ability. PERSPECTIVE: Pediatric patients seeking treatment for chronic back pain often present with substantial functional impairment that is not well explained by disease variables or pain intensity. Two important psychosocial variables (catastrophizing and familial pain history) may provide a context for a better understanding of pain-related disability in children.

Efficacy of cognitive-behavioral intervention for juvenile primary fibromyalgia syndrome.

OBJECTIVE: There are currently no controlled studies of behavioral interventions for juvenile primary fibromyalgia syndrome (JPFM). In this small-sample randomized study, we tested the efficacy of a behavioral intervention, i.e., coping skills training (CST), for the treatment of adolescents with JPFM. Outcomes tested in this study were functional disability, pain intensity, pain-coping efficacy, and depressive symptoms. METHODS: Thirty patients with JPFM were randomly assigned to 8 weeks of either CST or self-monitoring. Adolescents in the CST condition received training in active pain-coping techniques, while those in the self-monitoring condition monitored daily pain intensity and sleep quality with no instructions about behavior change. After posttreatment assessment, subjects were crossed over into the opposite treatment arm for 8 weeks (so that all adolescents eventually received both CST and self-monitoring) and were reassessed at Week 16. RESULTS: At Week 8, adolescents in both conditions showed significant decrease in depressive symptoms and functional disability. Those who received CST showed significantly greater ability to cope with pain than those in the self-monitoring condition and a trend toward decreased pain intensity. At Week 16, adolescents had significantly lower levels of disability and depressive symptoms compared to baseline, but those who received self-monitoring followed by CST seemed to receive the most benefit. CONCLUSION: CST can lead to improved functioning among JPFM patients. Although some of the improvement may be due to increased monitoring and attention, CST provides the specific benefit of improving adolescents' ability to cope with pain.