Needle-like structures discovered on positively charged lightning branches.

Lightning is a dangerous yet poorly understood natural phenomenon. Lightning forms a network of plasma channels propagating away from the initiation point with both positively and negatively charged ends-called positive and negative leaders1. Negative leaders propagate in discrete steps, emitting copious radio pulses in the 30-300-megahertz frequency band2-8 that can be remotely sensed and imaged with high spatial and temporal resolution9-11. Positive leaders propagate more continuously and thus emit very little high-frequency radiation12. Radio emission from positive leaders has nevertheless been mapped13-15, and exhibits a pattern that is different from that of negative leaders11-13,16,17. Furthermore, it has been inferred that positive leaders can become transiently disconnected from negative leaders9,12,16,18-20, which may lead to current pulses that both reconnect positive leaders to negative leaders11,16,17,20-22 and cause multiple cloud-to-ground lightning events1. The disconnection process is thought to be due to negative differential resistance18, but this does not explain why the disconnections form primarily on positive leaders22, or why the current in cloud-to-ground lightning never goes to zero23. Indeed, it is still not understood how positive leaders emit radio-frequency radiation or why they behave differently from negative leaders. Here we report three-dimensional radio interferometric observations of lightning over the Netherlands with unprecedented spatiotemporal resolution. We find small plasma structures-which we call 'needles'-that are the dominant source of radio emission from the positive leaders. These structures appear to drain charge from the leader, and are probably the reason why positive leaders disconnect from negative ones, and why cloud-to-ground lightning connects to the ground multiple times.

A large light-mass component of cosmic rays at 10(17)-10(17.5) electronvolts from radio observations.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Clinically relevant dual probe difference specimen imaging (DDSI) protocol for freshly resected breast cancer specimen staining.

BACKGROUND: Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow. METHODS: In previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to < 10-min whilst maintaining robust benign and malignant tissue differentiation. RESULTS: We evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation. CONCLUSIONS: Successful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.

Probing Atmospheric Electric Fields in Thunderstorms through Radio Emission from Cosmic-Ray-Induced Air Showers.

We present measurements of radio emission from cosmic ray air showers that took place during thunderstorms. The intensity and polarization patterns of these air showers are radically different from those measured during fair-weather conditions. With the use of a simple two-layer model for the atmospheric electric field, these patterns can be well reproduced by state-of-the-art simulation codes. This in turn provides a novel way to study atmospheric electric fields.

A guide to assessing physical activity using accelerometry in cancer patients.

Increased physical activity (PA) has been associated with a decreased risk for the occurrence and recurrence of many cancers. PA is an important outcome measure in rehabilitation interventions within cancer and may be used as a proxy measure of recovery or deterioration in health status following treatment and in the palliative care setting. PA is a complex multi-dimensional construct which is challenging to measure accurately. Factors such as technical precision and feasibility influence the choice of PA measurement tool. Laboratory-based methods are precise and mainly used for validation purposes, but their clinical applicability is limited. Self-report methods such as questionnaires are widely used due to their simplicity and reasonable cost; however, accuracy can be questionable. Objective methods such as pedometers measure step count but do not measure intensity, frequency or duration of activity. Accelerometers can measure PA behaviour at both ends of the movement spectrum from sedentary to vigorous levels of activity and can also provide objective data about the frequency, intensity, type and duration of PA. Balancing precision with ease of use, accelerometry may be the best measure of PA in cancer-based studies, but only a small number of studies have incorporated this measurement. This review will provide a background to PA and an overview of accelerometer measurement as well as technical and practical considerations, so this useful tool could be more widely incorporated into clinical trial research within cancer.

Testing the 'teachable moment' premise: does physical activity increase in the early survivorship phase?

PURPOSE: Little is known about objectively measured physical activity during the early survivorship period. This study measured physical activity, fatigue, and quality of life (QOL) in breast cancer patients over the first year after completion of chemotherapy and compared results to a matched non-cancer group. METHODS: Data was obtained from 24 breast cancer subjects (mean ± SD) 50.9 ± 12.8 years at time points of 6 weeks, 6 months and 1 year after completion of adjuvant chemotherapy and from 20 matched women. The following variables were assessed, physical activity (RT3 accelerometer and International Physical Activity Questionnaire), quality-of-life (EORTC QLQ C-30) and fatigue (Brief Fatigue Inventory). RESULTS: At 6 weeks after completion of chemotherapy, high levels of sedentary behaviour were found (6.8 ± 1.9 h sedentary per day), which did not improve, and was no different to the comparison group (6.5 ± 1.4 h). Less light activity was performed in the cancer cohort compared to the comparison group (p = 0.003). Body mass index (BMI) increased significantly in the cancer cohort (p = 0.015) and 1 year after chemotherapy finished only 13% (n = 3) had a BMI <25, while the comparable value was 45% (n = 9) in the non-cancer group. The QOL domain of cognitive function improved over the first 6 months (p = 0.034) but physical functioning declined (p = 0.008) over this time period. Fatigue did not change, and at the 1-year time point, 38% of the cancer patients (n = 11) reported high levels of fatigue. CONCLUSION: This study highlighted the unchanging sedentary behaviour and weight gain of breast cancer survivors during the first year after completion of chemotherapy, which may inform rehabilitation models in this population.

Multicenter, Prospective, Observational Study of Nonoperative Versus Operative Treatment for High-Energy Midshaft Clavicle Fractures.

OBJECTIVES: Evaluate if nonoperative or operative treatment of displaced clavicle fractures delivers reduced rates of nonunion and improved Disability of the Arm, Shoulder, and Hand (DASH) scores. DESIGN: Multicenter, prospective, observational. SETTING: Seven Level 1 Trauma Centers in the United States. PATIENT SELECTION CRITERIA: Adults with closed, displaced (100% displacement/shortened >1.5 cm) midshaft clavicle fractures (Orthopaedic Trauma Association 15.2) were treated nonoperatively, with plates and screw fixation, or with intramedullary fixation from 2003 to 2018. OUTCOME MEASURES AND COMPARISONS: DASH scores (2, 6 weeks, 3, 6, 12, and 24 months), reoperation, and nonunion were compared between the nonoperative, plate fixation, and intramedullary fixation groups. RESULTS: Four hundred twelve patients were enrolled, with 203 undergoing plate fixation, 26 receiving intramedullary fixation, and 183 treated nonoperatively. The average age of the nonoperative group was 40.1 (range 18-79) years versus 35.8 (range 18-74) in the plate group and 39.3 (range 19-56) in the intramedullary fixation group (P = 0.06). One hundred forty (76.5%) patients in the nonoperative group were male compared with 154 (75.9%) in the plate group and 18 (69.2%) in the intramedullary fixation group (P = 0.69). All groups showed similar DASH scores at 2 weeks, 12 months, and 24 months (P > 0.05). Plate fixation demonstrated better DASH scores (median = 20.8) than nonoperative (median = 28.3) at 6 weeks (P = 0.04). Intramedullary fixation had poorer DASH scores at 6 weeks, 3 months, and 6 months than plate fixation and worse DASH scores than nonoperative at 6 months (P < 0.05). The nonunion rate for nonoperative treatment (14.6%) was significantly higher than the plate group (0%) (P < 0.001). CONCLUSIONS: Operative treatment of displaced clavicle fractures provided lower rates of nonunion than nonoperative treatment. Except at 6 weeks, no difference was observed in DASH scores between plate fixation and nonoperative treatment. Intramedullary fixation resulted in worse DASH scores than plate fixation at 6 weeks, 3 months, and 6 months and worse DASH scores than nonoperative at 6 months. Implant removal was the leading reason for reoperation in the plate and intramedullary fixation groups, whereas surgery for nonunion was the primary reason for surgery in the nonoperative group. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The effect of aerobic exercise on metabolic and inflammatory markers in breast cancer survivors--a pilot study.

PURPOSE: Physical activity is associated with a reduced risk of breast cancer development and recurrence. There are several hypothesised mechanisms for this including positive effects on metabolic and inflammatory biomarkers and favourable changes in anthropometric variables. This pilot study examined the effect of an 8-week aerobic exercise intervention on several of these outcomes, including body composition, the metabolic syndrome, C-reactive protein (CRP) and physical activity, in breast cancer survivors 2-6 months post-chemotherapy. METHODS: Assessments were completed at baseline, at 8-weeks and 3-months post-intervention. Measures taken following a 12-h fast included body composition (bioimpedance analysis), metabolic syndrome (waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides and fasting glucose), insulin resistance (homeostatic model assessment), CRP and physical activity (accelerometry and questionnaire). Participants were randomized to either an 8-week moderate-intensity aerobic exercise group or a usual-care control group. Analysis was completed using repeated-measures analysis of variance (ANOVA) (p = 0.05). RESULTS: Twenty-six breast cancer survivors participated (mean (standard deviation) age 48.1 (8.8) years, exercise group; n = 16, control group; n = 10). At baseline, 13 participants were overweight, 6 were obese and 19 centrally obese. Intention-to-treat analysis revealed no significant differences between the exercise and control groups in any of the outcomes measures; however, analysis of those who adhered to >90 % of the supervised exercise class showed a significant decrease in waist circumference (p = 0.05) and a significant increase in subjectively reported "total weekly" (p = 0.005) activity. CONCLUSION: While this 8-week aerobic exercise pilot intervention did not elicit significant improvements in biomarkers of breast cancer risk, there was some suggestion of improvements in waist circumference and subjectively measured physical activity in participants with >90 % adherence to the programme. A trial of longer duration and greater subject numbers is warranted.

Osteoporotic hip fractures: the burden of fixation failure.

Osteoporotic hip fractures are a major cause of morbidity and mortality in the elderly. Furthermore, reduced implant anchorage in osteoporotic bone predisposes towards fixation failure and with an ageing population, even low failure rates represent a significant challenge to healthcare systems. Fixation failure in fragility fractures of the hip ranges from 5% in peritrochanteric fractures through to 15% and 41% in undisplaced and displaced fractures of the femoral neck, respectively. Our findings, in general, support the view that failed internal fixation of these fragility fractures carries a poor prognosis: it leads to a twofold increase in the length of hospital stay and a doubling of healthcare costs. Patients are more likely to suffer a downgrade in their residential status upon discharge with a consequent increase in social dependency. Furthermore, the marked disability and reduction in quality of life evident before salvage procedures may persist at long-term followup. The risk, of course, for the elderly patient with a prolonged period of decreased functioning is that the disability becomes permanent. Despite this, however, no clear link between revision surgery and an increase in mortality has been demonstrated in the literature.

Dual probe difference specimen imaging for prostate cancer margin assessment.

Significance: Positive margin status due to incomplete removal of tumor tissue during radical prostatectomy for high-risk localized prostate cancer requires reoperation or adjuvant therapy, which increases morbidity and mortality. Adverse effects of prostate cancer treatments commonly include erectile dysfunction, urinary incontinence, and bowel dysfunction, making successful initial curative prostatectomy imperative. Aim: Current intraoperative tumor margin assessment is largely limited to frozen section analysis, which is a lengthy, labor-intensive process that is obtrusive to the clinical workflow within the operating room (OR). Therefore, a rapid method for prostate cancer margin assessment in the OR could improve outcomes for patients. Approach: Dual probe difference specimen imaging (DDSI), which uses paired antibody-based probes that are labeled with spectrally distinct fluorophores, was shown herein for prostate cancer margin assessment. The paired antibody-based probes consisted of a targeted probe to prostate-specific membrane antigen (PSMA) and an untargeted probe, which were used as a cocktail to stain resected murine tissue specimens including prostate tumor, adipose, muscle, and normal prostate. Ratiometric images (i.e., DDSI) of the difference between targeted and untargeted probe uptake were calculated and evaluated for accuracy using receiver operator characteristic curve analysis with area under the curve values used to evaluate the utility of the DDSI method to detect PSMA positive prostate cancer. Results: Targeted and untargeted probe uptake was similar between the high and low PSMA expressing tumor due to nonspecific probe uptake after topical administration. The ratiometric DDSI approach showed substantial contrast difference between the PSMA positive tumors and their respective normal tissues (prostate, adipose, muscle). Furthermore, DDSI showed substantial contrast difference between the high PSMA expressing tumors and the minimally PSMA expressing tumors due to the ratiometric correction for the nonspecific uptake patterns in resected tissues. Conclusions: Previous work has shown that ratiometic imaging has strong predictive value for breast cancer margin status using topical administration. Translation of the ratiometric DDSI methodology herein from breast to prostate cancers demonstrates it as a robust, ratiometric technique that provides a molecularly specific imaging modality for intraoperative margin detection. Using the validated DDSI protocol on resected prostate cancers permitted rapid and accurate assessment of PSMA status as a surrogate for prostate cancer margin status. Future studies will further evaluate the utility of this technology to quantitatively characterize prostate margin status using PSMA as a biomarker.

Diagnosing the doctors' departure: survey on sources of dissatisfaction among Irish junior doctors.

There has been a significant decline in the number of applications for non-consultant hospital doctor (NCHD) posts in Ireland over the last 18 months. We conducted an online, anonymous survey of Irish NCHDs to establish levels of satisfaction, sources of dissatisfaction and the major reasons for junior doctors seeking work abroad. 522 NCHDs took the survey, including 64 (12.3%) currently working outside of the Republic. 219 (45.8%) were slightly dissatisfied and 142 (29.7%) were extremely dissatisfied with practising medicine in Ireland. Major sources of dissatisfaction included the state of the health care system, staffing cover for leave and illness, the dearth of consultant posts and the need to move around Ireland. The most important reason for NCHDs wishing to leave was to seek better training and career opportunities abroad.

MicroRNA therapeutics.

MicroRNAs (miRNAs) provide new therapeutic targets for many diseases, while their myriad roles in development and cellular processes make them fascinating to study. We still do not fully understand the molecular mechanisms by which miRNAs regulate gene expression nor do we know the complete repertoire of mRNAs each miRNA regulates. However, recent progress in the development of effective strategies to block miRNAs suggests that anti-miRNA drugs may soon be used in the clinic.

Markedly poor physical functioning status of people experiencing homelessness admitted to an acute hospital setting.

Adults who are homeless experience poor health and frequently require hospital in-patient care but the physical functioning ability of this group is rarely considered. The objective of this study was to evaluate a broad range of physical functioning variables to enable better future planning of targeted health and accommodation services for this group. This cross-sectional, observational study was conducted in a large acute hospital in Dublin, Ireland. A comprehensive ward-based test battery evaluated physical functioning in 65 in-patients registered as homeless with an age range of 23-80 years. Less than 10% (n = 5) were > 70 years. 58/65 (83%) of participants had mobility limitations and 35/65 (54%) reported at least one fall in the previous six months. Only 25/66 (35%) were able to walk for 6 min and 20/65 (31%) were able to climb one flight of stairs. 45/63 (70%) of participants were pre-frail or frail. Muscular mass was normal in the majority of participants but grip strength was low. This study revealed hospital in-patients registered as homeless displayed particularly poor physical functioning levels and mobility regardless of age. Health and housing services should address the unmet physical functioning needs of this vulnerable group.

A comparison of performances of consultant surgeons, NCHDs and medical students in a modified HPAT examination.

Following the implementation of the Fottrell report, entry to medical school in Ireland has undergone significant change. Medical school studentship is now awarded based on a combination of points obtained from the final examination of Irish secondary schools (the leaving certificate) combined with HPAT scores (Health Professions Admissions Test). The HPAT is designed to test a candidate's knowledge in several different fields including problem solving skills, logical and non verbal reasoning. A sample HPAT was administered to a test group composed of consultant surgeons, non consultant hospital doctors, and medical students. Statistical analysis was performed and no significant difference was found between the performances of the groups. This is surprising as it was expected that groups with greater experience at medical problem solving would have translated to higher scores. This exposes a flaw within the HPAT system and a potential weakness in the process of doctor selection.

Neisseria meningitidis as a Cause of Septic Arthritis: An Unusual Case of Periprosthetic Joint Infection.

One of the most feared complications after arthroplasty is infection due to its significant impact on patient morbidity. Infection may transfer to the joint at the time of surgery or be seeded, haematologically, to the prosthetic joint from another infection source. In this case, a 72-year-old female presented with symptoms of septic arthritis seven years after her original arthroplasty surgery. At presentation, she denied trauma and any comorbidity which would predispose her to infection. Culturing of samples taken revealed the patient was infected with Neisseria meningitidis, and the patient underwent a DAIR procedure. She continued postoperative long-term antimicrobial therapy with resolution of her infection. Follow-up at one year showed complete resolution of the patient's illness with a return to premorbid baseline. To our knowledge, this is the third reported case of septic arthritis caused by Neisseria meningitidis in a prosthetic joint in the literature.

Thyroid radiation shields: A potential source of intraoperative infection.

INTRODUCTION: Thyroid radiation shields are often uncovered by the surgical gown and may represent a preventable source of wound contamination. The aims of this study are to define the common pathogens found on thyroid radiation shields and evaluate the effectiveness of a simple cleaning method. METHODS: Samples were obtained from 29 community thyroid shields collected from the operating theatres of 3 teaching hospitals. Each shield was swabbed under strict sterile technique using a separate swab for each of 4 designated zones. After sampling, shields were cleaned with a readily available disinfectant and sampling was repeated after 5 min. All swabs were cultured in ambient air at 37 °C on 5% sheeps blood agar for 48 hrs and subsequent growth was identified by a MALDI-TOF Walkaway mass spectrometer. RESULTS: Before cleaning, 100% of thyroid shields (29/29) and 68% of shield zones (79/116) grew at least 1 type of bacteria. Coagulase negative staphylococci, including S. epidermidis, S. capitis, S. cohnii, S. haemolyticus and S. hominis, were most commonly isolated. Enterobacteriaceae and S. aureus were also cultured. After cleaning, culturable contamination was reduced by 86.3% and 64.5%, respectively (p < 0.001). CONCLUSION: The most common pathogens associated with SSIs can be isolated on thyroid radiation shields. Appropriate cleaning of thyroid shields with readily available disinfectant can significantly reduce the bacterial burden as detectable by culture. Hospitals should facilitate staff education and reinforce their policies on cleaning these shields which may often be overlooked.

Near-infrared nerve-binding fluorophores for buried nerve tissue imaging.

Nerve-binding fluorophores with near-infrared (NIR; 650 to 900 nm) emission could reduce iatrogenic nerve injury rates by providing surgeons precise, real-time visualization of the peripheral nervous system. Unfortunately, current systemically administered nerve contrast agents predominantly emit at visible wavelengths and show nonspecific uptake in surrounding tissues such as adipose, muscle, and facia, thus limiting detection to surgically exposed surface-level nerves. Here, a focused NIR fluorophore library was synthesized and screened through multi-tiered optical and pharmacological assays to identify nerve-binding fluorophore candidates for clinical translation. NIR nerve probes enabled micrometer-scale nerve visualization at the greatest reported tissue depths (~2 to 3 mm), a feat unachievable with previous visibly emissive contrast agents. Laparoscopic fluorescent surgical navigation delineated deep lumbar and iliac nerves in swine, most of which were invisible in conventional white-light endoscopy. Critically, NIR oxazines generated contrast against all key surgical tissue classes (muscle, adipose, vasculature, and fascia) with nerve signal-to-background ratios ranging from ~2 (2- to 3-mm depth) to 25 (exposed nerve). Clinical translation of NIR nerve-specific agents will substantially reduce comorbidities associated with surgical nerve damage.