Gluteal lymphoedema associated with lower extremity lymphoedema: A preliminary study with indocyanine green lymphography and magnetic resonance imaging.

INTRODUCTION: Indocyanine green (ICG) lymphography studies have identified that one in three to five patients with cancer-related lower extremity lymphoedema (LEL) demonstrated dermal backflow extending to the gluteal region. This study aimed to further characterize gluteal lymphoedema using contemporaneous magnetic resonance imaging (MRI). PATIENTS AND METHODS: Twenty-eight patients with unilateral advanced LEL who underwent both ICG lymphography and MRI prior to any surgical procedure were included in this study. The patients were divided into two groups with/without gluteal lymphoedema by the presence of dermal backflow on ICG lymphography. MRI was used to evaluate tissue changes. RESULTS: Ten patients demonstrated gluteal lymphoedema on ICG lymphography and had a higher incidence of skin hypertrophy in the gluteal region. However, no difference in excess leg volume was found between the two groups. A trend of increasing gluteal subcutaneous tissue in the affected side was identified in patients with gluteal lymphoedema with a median increase of 20% compared with an 11% increase in the non-gluteal lymphoedema group. The excess gluteal subcutaneous tissue was positively correlated to ipsilateral excess leg volume. CONCLUSION: The gluteal lymphoedema group on ICG lymphography had skin thickening in the gluteal region and was likely identified in the secondary cancer-related group. Surgical and conservative management options for gluteal lymphoedema need to be considered in advanced LEL.

The Impact of Rate Formulations on Stochastic Molecular Motor Dynamics.

Cells are complex structures which require considerable amounts of organization via transport of large intracellular cargo. While passive diffusion is often sufficiently fast for the transport of smaller cargo, active transport is necessary to organize large structures on the short timescales necessary for biological function. The main mechanism of this transport is by cargo attachment to motors which walk in a directed fashion along intracellular filaments. There are a number of models which seek to describe the motion of motors with attached cargo, from detailed microscopic to coarse phenomenological descriptions. We focus on the intermediate-detailed discrete stochastic hopping models, and explore how cargo transport changes depending on the number of motors, motor interaction, system constraints and rate formulations, which are derived from common thermodynamic assumptions. We find that, despite obeying the same detailed balance constraint, the choice of rate formulation considerably affects the characteristics of the overall motion of the system, with one rate formulation exhibiting novel behavior of loaded motor groups moving faster than a single unloaded motor.

A very-high-energy component deep in the γ-ray burst afterglow.

Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Molecular self-assembly of substituted terephthalic acids at the liquid/solid interface: investigating the effect of solvent.

Self-assembly of three related molecules - terephthalic acid and its hydroxylated analogues - at liquid/solid interfaces (graphite/heptanoic acid and graphite/1-phenyloctane) has been studied using a combination of scanning tunnelling microscopy and molecular mechanics and molecular dynamics calculations. Brickwork-like patterns typical for terephthalic acid self-assembly have been observed for all three molecules. However, several differences became apparent: (i) formation or lack of adsorbed monolayers (self-assembled monolayers formed in all systems, with one notable exception of terephthalic acid at the graphite/1-phenyloctane interface where no adsorption was observed), (ii) the size of adsorbate islands (large islands at the interface with heptanoic acid and smaller ones at the interface with 1-phenyloctane), and (iii) polymorphism of the hydroxylated terephthalic acids' monolayers, dependent on the molecular structure and/or solvent. To rationalise this behaviour, molecular mechanics and molecular dynamics calculations have been performed, to analyse the three key aspects of the energetics of self-assembly: intermolecular, substrate-adsorbate and solvent-solute interactions. These energetic characteristics of self-assembly were brought together in a Born-Haber cycle, to obtain the overall energy effects of formation of self-assembled monolayers at these liquid/solid interfaces.

Improving Hospital at Home for frail older people: insights from a quality improvement project to achieve change across regional health and social care sectors.

BACKGROUND: Against a background of rising numbers of frail older people, there is a need to improve quality and safety of services whilst containing costs. Improving patient outcomes requires change across hospital and community systems. Our objective was to change practice in order to deliver a Hospital at Home programme (admission avoidance and early supported discharge) for frail older people across a regional commissioning area. The programme, undertaken within the Northern, Eastern & Western Devon Clinical Commissioning Group (CCG) sub-localities of Exeter (population 120,000) and Woodbury, Exmouth and Budleigh Salterton (towns with populations of around 10,000), involved reconfiguration of existing services rather than being a stand-alone intervention. METHODS: Quality Improvement methodology, with hospital and community staff using Plan-Do-Study-Act (PDSA) cycles to implement and test service changes. OUTCOME MEASURES: 1) Discharge destination; 2) Length of stay; 3) Acute Community Team referrals. RESULTS: Against a backdrop of intense financial pressures, significant community bed closures, and difficult relations between hospital and community services, outcomes remained stable (discharge destination, length of hospital stay, and number of referrals to the community team). CONCLUSION: PDSA cycles enabled stakeholders across acute and community services to be involved, promoted a process of collaborative inquiry and ownership of findings, and improved motivation to act on results and produce change. Practitioners and managers seeking to improve the delivery of complex, cross-cutting services in other areas can learn from the experience of applying Quality Improvement methods reported here.

H.E.S.S. Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center.

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

Urothelial cells undergo epithelial-to-mesenchymal transition after exposure to muscle invasive bladder cancer exosomes.

Bladder cancer, the fourth most common noncutaneous malignancy in the United States, is characterized by high recurrence rate, with a subset of these cancers progressing to a deadly muscle invasive form of disease. Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA, thus potentially modulating signaling pathways in recipient cells. Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal stem cells. EMT has been implicated in the initiation of metastasis for cancer progression. We investigated the ability of bladder cancer-shed exosomes to induce EMT in urothelial cells. Exosomes were isolated by ultracentrifugation from T24 or UMUC3 invasive bladder cancer cell conditioned media or from patient urine or bladder barbotage samples. Exosomes were then added to the urothelial cells and EMT was assessed. Urothelial cells treated with bladder cancer exosomes showed an increased expression in several mesenchymal markers, including α-smooth muscle actin, S100A4 and snail, as compared with phosphate-buffered saline (PBS)-treated cells. Moreover, treatment of urothelial cells with bladder cancer exosomes resulted in decreased expression of epithelial markers E-cadherin and ß-catenin, as compared with the control, PBS-treated cells. Bladder cancer exosomes also increased the migration and invasion of urothelial cells, and this was blocked by heparin pretreatment. We further showed that exosomes isolated from patient urine and bladder barbotage samples were able to induce the expression of several mesenchymal markers in recipient urothelial cells. In conclusion, the research presented here represents both a new insight into the role of exosomes in transition of bladder cancer into invasive disease, as well as an introduction to a new platform for exosome research in urothelial cells.

Antidepressant-like responses to lithium in genetically diverse mouse strains.

A mood stabilizing and antidepressant response to lithium is only found in a subgroup of patients with bipolar disorder and depression. Identifying strains of mice that manifest differential behavioral responses to lithium may assist in the identification of genomic and other biologic factors that play a role in lithium responsiveness. Mouse strains were tested in the forced swim test (FST), tail suspension test (TST) and open-field test after acute and chronic systemic and intracerebroventricular (ICV) lithium treatments. Serum and brain lithium levels were measured. Three (129S6/SvEvTac, C3H/HeNHsd and C57BL/6J) of the eight inbred strains tested, and one (CD-1) of the three outbred strains, showed an antidepressant-like response in the FST following acute systemic administration of lithium. The three responsive inbred strains, as well as the DBA/2J strain, displayed antidepressant-like responses to lithium in the FST after chronic administration of lithium. However, in the TST, acute lithium resulted in an antidepressant-like effect only in C3H/HeNHsd mice. Only C57BL/6J and DBA/2J showed an antidepressant-like response to lithium in the TST after chronic administration. ICV lithium administration resulted in a similar response profile in BALB/cJ (non-responsive) and C57BL/6J (responsive) strains. Serum and brain lithium concentrations showed that behavioral results were not because of differential pharmacokinetics of lithium in individual strains, suggesting that genetic factors likely regulate these behavioral responses to lithium. Our results indicate that antidepressant-like responses to lithium in tests of antidepressant efficacy varies among genetically diverse mouse strains. These results will assist in identifying genomic factors associated with lithium responsiveness and the mechanisms of lithium action.

Potentially preventable tuberculosis among HIV-infected persons in the era of highly active antiretroviral treatment.

OBJECTIVE: To characterize the proportion of tuberculosis (TB) cases that could have been prevented among human immunodeficiency virus (HIV) infected persons receiving care in the era of highly active antiretroviral treatment (HAART). DESIGN: We conducted an observational cohort study among HIV-infected patients with >or=2 out-patient visits at the Comprehensive Care Center, Nashville, Tennessee, USA, between 1 January 1998 and 31 December 2005. METHODS: A potentially preventable TB case was defined as a case in which the patient received no screening tuberculin skin test (TST) prior to TB diagnosis or a case in which a patient with a positive screening TST did not complete treatment for latent infection. RESULTS: Of 3601 HIV-infected persons in care (13 905 person-years [p-y] of follow-up), 29 developed TB (230/100,000 p-y). Of the 29, 20 (69%) had not had TST performed as part of routine screening. Of the nine patients screened, four had a positive test, three of whom completed treatment for latent TB infection. Of 29 TB cases, 21 (72%) were therefore potentially preventable. CONCLUSIONS: Most TB cases in this cohort were potentially preventable had the patients undergone a screening TST followed by treatment of latent infection if they had a positive TST.

Public exposure to radio waves near GSM microcell and picocell base stations.

Exposures of the general public to radio waves at locations near 20 randomly selected GSM microcell and picocell base stations in the UK have been assessed in the context of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. Compliance distances were calculated for the antennas of the base stations from their reported radiated powers. Under pessimistic assumptions that would maximise exposures, the minimum height at which the general public reference level could potentially be exceeded near any of the base station antennas was calculated to be 2.4 m above ground level. The power densities of the broadcast carriers transmitted by the base stations have been measured and scaled to include all other possible carriers. Exposures were generally in the range 0.002-2% of the ICNIRP general public reference level, and the greatest exposure quotient near any of the base stations was 8.6%. Exposures close to microcell base stations were found to be generally greater than those close to macrocell base stations.

Assessment of occupational exposure to radiofrequency fields and radiation.

The use of personal monitors for the assessment of exposure to radiofrequency fields and radiation in potential future epidemiological studies of occupationally exposed populations has been investigated. Data loggers have been developed for use with a commercially available personal monitor and these allowed personal exposure records consisting of time-tagged measurements of electric and magnetic field strength to be accrued over extended periods of the working day. The instrumentation was worn by workers carrying out tasks representative of some of their typical daily activities at a variety of radio sites. The results indicated significant differences in the exposures of workers in various RF environments. A number of measures of exposure have been examined with a view to assessing possible exposure metrics for epidemiological studies. There was generally a good correlation between a given measure of electric field strength and the same measure of magnetic field strength.

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

A one-year experience with a capitated health care plan for infertility.

OBJECTIVE: To report on a one-year experience participating in a capitated healthcare plan for infertility. DESIGN: Prospective study. SETTING: University population. PATIENT(S): Reproductive-age women 15 to 50 years. INTERVENTION(S): The first-generation Lewin infertility algorithm and CATHI software were used to negotiate infertility services under a capitated arrangement for $0.50 per member per month. The following reports our experience for the fiscal year 1997. MAIN OUTCOME MEASURE(S): Infertility services rendered, pregnancy rate, cost of services, collection rates. RESULT(S): Five thousand forty-six women representing 39,689 member months generated 39 new and 198 return visits. Thirty-two percent of the patients required three visits or less; six patients generated 22% of the visits. Fifty-one percent listed infertility as one of their chief complaints; 31% had mixed diagnoses. Eight (7.6%) patients required surgery, 11 (10.5%) patients underwent either IVF or GIFT cycles. Total charges submitted were $176,636; the amount assigned to specialty care was $135,277, and to IVF/GIFT, $33,433. Total capitated payments, including copayments, was $126,256 under the reproductive medicine agreement and $32,891 under the infertility rider. This resulted in a 71% gross collections rate. CONCLUSION(S): This study indicates that entering into a capitated health care plan to provide an infertility benefit can produce a successful result.

The holmium:yttrium-aluminum-garnet laser in wrist arthroscopy: a five-year experience in the treatment of central triangular fibrocartilage complex tears by partial excision.

Arthroscopic debridement of the articular disk is an accepted method for the treatment of symptomatic central tears of the triangular fibrocartilage complex. Current techniques use punches, knives, and shavers to debride the torn disk back to a stable peripheral rim. The holmium:yttrium-aluminum-garnet laser offers an alternative method for disk debridement with potential advantages of enhanced speed, precision, and hemostasis. We present a retrospective review of 35 patients who underwent arthroscopic laser debridement for a Palmer type IA tear in the triangular fibrocartilage complex. Overall response to treatment was good to excellent in 68% of patients and return to work was seen in 88%. One patient developed a deep wound infection. Clinical results after arthroscopic laser debridement are comparable to those reported by other investigators using conventional techniques.

Constructing a financial case for a computerized patient data management system (PDMS) in a cardiothoracic intensive care unit.

A number of claims are made for computerized patient data management systems (PDMS) which make them of interest to medical and nursing staff who wish to optimize patient care. Comparatively little has been published concerning cost effectiveness of these systems. In this article a financial case is put forward based on the premise that a PDMS can save nursing time, and this saving can then be translated into employing a smaller nursing workforce. An analysis of the relevant costs suggests that over an 8-year period these systems can show substantial profits, but it is also suggested that more research is required to substantiate this finding.

Safety and acceptability of a baggy latex condom.

A total of 104 couples participated in a randomized crossover trial to compare a new baggy condom with a straight-shaft condom produced by the same manufacturer. Participants completed a coital log after using each condom. All couples used five condoms of each type. Among 102 couples who did not report major deviations from the protocol, the breakage rate was eight of 510 (1.6%) for the baggy condom, and six of 510 (1.2%) for the standard condom (rate difference, RD = 0. 4%, 95% confidence interval of the RD, CI = -1.0%; +1.8%). Slippage was reported in 50 baggy condom logs and in 58 standard condom logs; the slippage rate was 50 of 510 (9.8%) for the baggy condom, and 58 of 510 (11.4%) for the standard condom (RD = -1.6%, 95% CI = -5.4%; +2.2%). Slippage was most often partial (<1 inch) and may not indicate condom failure. Severe slippage rates were 11 of 510 (2.2%) for the baggy condom, and 18 of 510 (3.5%) for the standard condom (RD = -1.4%, 95% CI = -3.4%; +0.7%). The findings support the conclusion that the two condoms are equivalent with respect to breakage and slippage. The participants appeared to prefer the baggy condom, suggesting that the new product may be more acceptable to the public than the traditional straight-shaft condoms, and may be easier to use consistently over long time periods.

Hidden costs of infertility treatment in employee health benefits plans.

OBJECTIVES: Many employers exclude infertility treatment from coverage under their health benefits plans. However, infertility treatment is often provided under other diagnoses or in association with therapy rendered for other disease processes. This study attempted to estimate those hidden costs and to determine what the impact would be of providing coverage for infertility treatment. STUDY DESIGN: A 1-year retrospective analysis was carried out to isolate the hidden costs of infertility treatment from specific medical claims data gathered from a large representative employer with no infertility benefit provided. Data were analyzed in the context of the claims experience of a health plan covering approximately 28,000 employees. Infertility treatment was excluded under this plan. Medical claims for specific procedures and diagnoses in 1996 were analyzed by using Current Procedural Terminology codes in conjunction with International Classification of Diseases, Ninth Revision codes to estimate the hidden costs of infertility treatment. Forty-one Current Procedural Terminology codes and 68 International Classification of Diseases, Ninth Revision codes were used for the analysis. Clinical practice experience was used to set boundaries (conservative and moderate estimate) regarding the likelihood of a given treatment being associated with infertility. This was compared with 100% covered charges to generate claims per employee per month. Procedures covered operative, diagnostic, and laboratory services. These figures were used to compute a range of cost for infertility treatment per member per month. RESULTS: Forty-one Current Procedural Terminology codes were identified that indicated possible infertility treatment. These covered the areas of laparoscopic and hysteroscopic surgery, lysis of adhesions, neosalpingostomy, cyst drainage, oocyte retrieval or embryo transfer, echography, and various hormonal analyses. Sixty-eight International Classification of Diseases, Ninth Revision codes indicated the possibility of infertility treatment. These included endocrine disorders, various uterine pathologic conditions, pelvic pain, endometriosis, pregnancy loss, irregular menses, and various ovulatory dysfunctions. The retrospective analysis found that 35 Current Procedural Terminology codes were involved in claims highly indicative of infertility services, such as 56353, hysteroscopic division of uterine septum, and 58345, transcervical fallopian tube catheterization. According to the 35 Current Procedural Terminology codes, $603,807.95 would have been paid if 100% of the charges had been covered; this would have resulted in a claim per employee per month of $1.12 by conservative estimate to $0.60 by moderate estimate. Computed cost figures per member per month showed the hidden costs of infertility to range between $0.27 and $0.50. CONCLUSION: On the basis of various cost studies, rate filings, and employee data, the cost of providing coverage for infertility treatment has previously been shown to vary between $0.20 and $2.00 per member per month. Through appropriate cost sharing, managed care, and algorithms, infertility coverage can be offered at a cost of $0.40 to $0.50 per member per month. This analysis indicates that at least some employers already pay this much even when infertility is specifically excluded under the plan.