Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Melatonin as a treatment for mood disorders: a systematic review.

OBJECTIVE: Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders. METHOD: We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo. RESULTS: Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study. CONCLUSION: There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research.

Social activity and relationship changes experienced by people with bowel and bladder dysfunction following spinal cord injury.

STUDY DESIGN: Exploratory qualitative. OBJECTIVES: The aim of this study was to describe the experiences of bowel and bladder dysfunction on social activities and relationships in people with spinal cord injury living in the community. SETTING: People living with spinal cord injury experiencing bowel and bladder dysfunction. METHODS: Participants were recruited through the Australian Quadriplegic Association Victoria. Semi-structured in-depth interviews were undertaken with purposively selected participants to ensure representation of age, gender, spinal cord injury level and compensation status. A thematic analysis was performed to interpret patient experiences. RESULTS: Twenty-two participants took part in the study. Bladder and bowel dysfunction altered relationships because of issues with intimacy, strained partner relationships and role changes for family and friends. A lack of understanding from friends about bladder and bowel dysfunction caused frustration, as this impairment was often responsible for variable attendance at social activities. Issues with the number, location, access and cleanliness of bathrooms in public areas and in private residences negatively affected social engagement. Social activities were moderated by illness, such as urinary tract infections, rigid and unreliable bowel routines, stress and anxiety about incontinence and managing the public environment, and due to continuous changes in plans related to bowel and bladder issues. Social support and adaptation fostered participation in social activities. CONCLUSION: Tension exists between managing bowel and bladder dysfunction and the desire to participate in social activities. Multiple intersecting factors negatively affected the social relationships and activities of people with spinal cord injury and bowel and bladder dysfunction.

Delivering quality improvements in patient care: the application of the Leicester Model of interprofessional education.

BACKGROUND: This paper places the importance of evidence-based models of interprofessional education (IPE) within the context of a changing National Health Service (NHS). The coalition government has placed integrated care at the heart of its vision for England's health system. Its principles are to put patients at the centre of the NHS, empower clinicians to lead commissioning and change the emphasis of measurement to quality clinical outcomes. As a result, NHS services are being increasingly tendered along evidence-based care pathways and commissioners are introducing payment by results tariffs, requiring providers to achieve quality outcomes as a requirement of full payment. AIM: We argue that in preparing the health and social care workforce for outcome-based practice, the development of technical skills should be complemented with skills for effective teamworking and collaborative practice. METHODS: This paper shares the achievements of the Leicester Model of IPE which is underpinned by theoretical models of learning and implemented entirely in clinical practice; mixed research methods demonstrate that its learning potential is as relevant today as when it was first implemented in 1996. RESULTS: Our extensive research evidence demonstrates that students and healthcare professionals undertaking these programmes are enabled to perceive care pathways from service and providers perspectives; they gain valuable insights into how teams balance task- and patient-related issues, offer clarity about the team's effectiveness and gain new insights into collaborative opportunities to address patients' needs. CONCLUSION: We demonstrate that models such as ours offer evidence-based solutions which will support the achievement of quality outcomes for service providers, many of whom are reviewing their business plans to address the financial implications of payment by results. The current NHS reforms provide a hugely important lever in which IPE can come of age - in return we need to ensure that our NHS colleagues are informed of its potential.

Best strategies to recruit and enroll elderly Blacks into clinical and biomedical research.

BACKGROUND: Historically, Blacks have been disproportionately underrepresented in clinical trials. Outcomes associated with low Blacks' participation in research include poor understanding of the predictors and treatment of the disease, increasing health disparities, poor health equity, and suboptimal wellness of the nation as a whole. To address this gap in research participation, we analyzed our recruitment data to identify the most effective strategies for enrolling older Blacks in clinical trials. METHODS: Data used in these analyses were obtained from 3,266 potential volunteers, ages 50 or older, who completed a Mini-Mental State Exam as part of recruitment and screening for various clinical studies on Alzheimer's disease. In order to determine the most effective strategies for engaging Blacks in clinical research, we used tests of proportion to assess significant differences in recruitment sources, counts, and percentages for optimal recruitment strategies by gender. Finally, we employed regression analyses to confirm our findings. RESULTS: Of the total 3,266 screened, 2,830 Black volunteers were identified for further analysis. Overall, more women than men (73.8% vs 26.2%) participated in our recruitment activities. However, a significantly higher proportion of men than women were engaged through family (3.86% vs 1.30%, p=0.0004) and referral sources (5.89% vs 2.59%, p=0.0005). Compared to other sources for recruitment, we encountered a higher proportion of volunteers at health fairs (42.95%), and through advertisements (14.97%). In our sample, years of education and age did not appear to influence the likelihood of an encounter, screening, and potential participation. CONCLUSION: Our findings indicate Black men and women in our sample were predominantly recruited from health fairs and through advertisements tailored to their health needs and interests. Conversely, we mostly engaged Black men through family referrals and persons known to them, indicating a need for trust in their decision to engage study personnel and/or participate in clinical trials.

Digital Food Records in Community-Based Interventions: Mixed-Methods Pilot Study.

BACKGROUND: A pressing need exists to understand and optimize the use of dietary assessment tools that can be used in community-based participatory research (CBPR) interventions. A digital food record, which uses a mobile device to capture the dietary intake through text and photography inputs, is a particularly promising mobile assessment method. However, little is understood about the acceptability and feasibility of digital food records in CBPR and how to best tailor dietary assessment tools to the needs of a community. OBJECTIVE: The objective of our study was to evaluate the acceptability and feasibility of digital food records among church-based populations in resource-limited wards of Washington, DC, USA, using a mixed-methods approach. METHODS: This community-based pilot study was conducted as part of the Washington, DC Cardiovascular Health and Needs Assessment. Participants (n=17) received a mobile device (iPod Touch) to photodocument their dietary intake for a 3-day digital food record using a mobile app, FitNinja (Vibrent Health). The acceptability of the digital food record was explored through the thematic analysis of verbatim transcripts from a moderated focus group (n=8). In addition, the feasibility was evaluated by the percentage of participants complying with instructions (ie, capturing both before and after meal photos for at least 2 meals/day for 3 days). RESULTS: Qualitative themes identified were related to (1) the feasibility and acceptability of the mobile device and app, including issues in recording the dietary information and difficulty with photodocumentation; (2) suggestions for additional support and training experiences; and (3) comparisons with other mobile apps. Overall, the participants accepted the digital food record by demonstrating satisfaction with the tool and intent to continue the use (eg, participants recorded an average of 5.2, SD 7, consecutive days). Furthermore, of the 17 participants, 15 photodocumented at least 1 meal during the study period and 3 fully complied with the digital food record instructions. CONCLUSIONS: This study demonstrated digital food records as an acceptable tool in CBPR and identified contributors and barriers to the feasibility of digital food records for future research. Engaging community members in the implementation of novel assessment methods allows for the tailoring of technology to the needs of the community and optimizing community-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01927783; https://www.clinicaltrials.gov/ct2/show/NCT01927783 (Archived by WebCite at http://www.webcitation.org/70WzaFWb6).

Stability of A-150 plastic ionisation chamber response over a approximately 30-y period.

At the Northern Illinois University Institute for Neutron Therapy at Fermilab, the clinical tissue-equivalent ionisation chamber response is measured every treatment day using a cesium source that was configured to match readings obtained at the National Bureau of Standards. Daily measurements are performed in air using the air-to-tissue dose conversion factors given in AAPM Report #7. The measured exposure calibration factors have been tabulated and graphed as a function of time from 1978 to present. For A-150 plastic ionisation chambers, these factors exhibit a sinusoidal variation with a period of approximately 1 y and amplitude of +/- 1%. This variation, attributable to the hygroscopic nature of A-150 plastic, is correlated with the relative humidity of the facility, and is greater than the humidity corrections for gas described in the literature. The data suggest that chamber calibration should be performed at least weekly to accommodate these variations.

Calibration of the borated ion chamber at NIST reactor thermal column.

In boron neutron capture therapy and boron neutron capture enhanced fast neutron therapy, the absorbed dose of tissue due to the boron neutron capture reaction is difficult to measure directly. This dose can be computed from the measured thermal neutron fluence rate and the (10)B concentration at the site of interest. A borated tissue-equivalent (TE) ion chamber can be used to directly measure the boron dose in a phantom under irradiation by a neutron beam. Fermilab has two Exradin 0.5 cm(3) Spokas thimble TE ion chambers, one loaded with boron, available for such measurements. At the Fermilab Neutron Therapy Facility, these ion chambers are generally used with air as the filling gas. Since alpha particles and lithium ions from the (10)B(n,alpha)(7)Li reactions have very short ranges in air, the Bragg-Gray principle may not be satisfied for the borated TE ion chamber. A calibration method is described in this paper for the determination of boron capture dose using paired ion chambers. The two TE ion chambers were calibrated in the thermal column of the National Institute of Standards and Technology (NIST) research reactor. The borated TE ion chamber is loaded with 1,000 ppm of natural boron (184 ppm of (10)B). The NIST thermal column has a cadmium ratio of greater than 400 as determined by gold activation. The thermal neutron fluence rate during the calibration was determined using a NIST fission chamber to an accuracy of 5.1%. The chambers were calibrated at two different thermal neutron fluence rates: 5.11 x 10(6) and 4.46 x 10(7)n cm(-2) s(-1). The non-borated ion chamber reading was used to subtract collected charge not due to boron neutron capture reactions. An optically thick lithium slab was used to attenuate the thermal neutrons from the neutron beam port so the responses of the chambers could be corrected for fast neutrons and gamma rays in the beam. The calibration factor of the borated ion chamber was determined to be 1.83 x 10(9) +/- 5.5% (+/- 1sigma) n cm(-2) per nC at standard temperature and pressure condition.

Adherence with physical activity monitoring wearable devices in a community-based population: observations from the Washington, D.C., Cardiovascular Health and Needs Assessment.

Wearable mobile health (mHealth) technologies offer approaches for targeting physical activity (PA) in resource-limited, community-based interventions. We sought to explore user characteristics of PA tracking, wearable technology among a community-based population within a health and needs assessment. In 2014-2015, we conducted the Washington, D.C., Cardiovascular Health and Needs Assessment in predominantly African-American churches among communities with higher obesity rates and lower household incomes. Participants received a mHealth PA monitor and wirelessly uploaded PA data weekly to church data collection hubs. Participants (n = 99) were 59 ± 12 years, 79% female, and 99% African-American, with a mean body mass index of 33 ± 7 kg/m2. Eighty-one percent of participants uploaded PA data to the hub and were termed "PA device users." Though PA device users were more likely to report lower household incomes, no differences existed between device users and non-users for device ownership or technology fluency. Findings suggest that mHealth systems with a wearable device and data collection hub may feasibly target PA in resource-limited communities.

Community Engagement to Optimize the Use of Web-Based and Wearable Technology in a Cardiovascular Health and Needs Assessment Study: A Mixed Methods Approach.

BACKGROUND: Resource-limited communities in Washington, D.C. have high rates of obesity-related cardiovascular disease in addition to inadequate physical activity (PA) facilities and limited Internet access. Engaging community members in the design and implementation of studies to address these health disparities is essential to the success of community-based PA interventions. OBJECTIVE: The objective of the study was to use qualitative and quantitative methods to evaluate the feasibility and acceptability of PA-monitoring wristbands and Web-based technology by predominantly African American, church-based populations in resource-limited Washington, D.C. neighborhoods. METHODS: To address cardiovascular health in at-risk populations in Washington, D.C., we joined community leaders to establish a community advisory board, the D.C. Cardiovascular Health and Obesity Collaborative (D.C. CHOC). As their first initiative, the Washington, D.C. Cardiovascular Health and Needs Assessment intends to evaluate cardiovascular health, social determinants of health, and PA-monitoring technologies. At the recommendation of D.C. CHOC members, we conducted a focus group and piloted the proposed PA-monitoring system with community members representing churches that would be targeted by the Cardiovascular Health and Needs Assessment. Participants (n=8) agreed to wear a PA-monitoring wristband for two weeks and to log cardiovascular health factors on a secure Internet account. Wristbands collected accelerometer-based data that participants uploaded to a wireless hub at their church. Participants agreed to return after two weeks to participate in a moderated focus group to share experiences using this technology. Feasibility was measured by Internet account usage, wristband utilization, and objective PA data. Acceptability was evaluated through thematic analysis of verbatim focus group transcripts. RESULTS: Study participants (5 males, 3 females) were African American and age 28-70 years. Participant wristbands recorded data on 10.1±1.6 days. Two participants logged cardiovascular health factors on the website. Focus group transcripts revealed that participants felt positively about incorporating the device into their church-based populations, given improvements were made to device training, hub accessibility, and device feedback. CONCLUSIONS: PA-monitoring wristbands for objectively measuring PA appear to be a feasible and acceptable technology in Washington, D.C., resource-limited communities. User preferences include immediate device feedback, hands-on device training, explicit instructions, improved central hub accessibility, and designation of a church member as a trained point-of-contact. When implementing technology-based interventions in resource-limited communities, engaging the targeted community may aid in early identification of issues, suggestions, and preferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT01927783; https://clinicaltrials.gov/ct2/show/NCT01927783 (Archived by WebCite at http://www.webcitation.org/6f8wL117u).

Advanced diagnostic imaging and surgical treatment of an odontogenic retromasseteric abscess in a guinea pig.

A two-year-old guinea pig presented for difficulty chewing. Examination and diagnostic imaging, including computed tomography and magnetic resonance, revealed an odontogenic retromasseteric abscess associated with a mandibular cheek tooth. Treatment included removal of the abscess and marsupialisation of the surgical site for repeated debridement and healing by second intention. Unique features of this case included the use of advanced diagnostic imaging and utilisation of marsupialisation for surgical correction.

Gerstmann-Sträussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients.

We present two patients with Gerstmann-Sträussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129.

An update on malignant salivary gland tumors treated with neutrons at Fermilab.

One hundred and thirteen cases of recurrent and/or unresectable malignant salivary gland tumors, treated with fast neutron therapy at Fermilab between September 1976 and December 1984, are analyzed for local control, sites of failure, and treatment-related morbidity. Sixty-three patients had major and 55 had minor salivary gland tumors. Local control was achieved in 67% of patients with major and 58% of patients with minor salivary gland tumors. In the subgroup of patients with oropharyngeal and oral cavity lesions, 19/24 (80%) had local control. However, only four of 15 patients with maxillary antrum tumors had successful control of their disease. Seventy-four percent of patients with lesions measuring 5 cm or less and 30% of patients with larger lesions had their local disease controlled. Histology did not influence the local control rate. Both observed and adjusted median survival for patients with major salivary gland tumors was 36 months. Disease-free survival was 31 months. Observed and adjusted median survivals for patients with minor salivary gland tumors are 48 and 57 months respectively. Twenty of 86 patients (23%) had major morbidity; this was directly related to the total dose delivered. In the dose range 20-24 Gy the complication rate was 16%. Most of these complications were successfully managed with minimal functional disability. We have concluded that fast neutron irradiation is an appropriate treatment for malignant salivary gland tumors.

Normal tissue reactions and complications following high-energy neutron beam therapy: I. Crude response rates.

The incidence of significant complications (fibrosis, ulceration, necrosis of bone or soft tissue or serious functional impairment) was determined in relation to neutron dosage and follow-up time for 5 anatomical sites totalling 617 patients who had survived 2 or more years following treatment. The regions studied were head and neck (268 patients), thorax (lung and esophagus, 76 patients), upper abdomen (132 patients), pelvis (prostate and bladder, 114 patients) and extremities (27 patients). Neutron doses ranged from 16 to 28 Gy. All patients were followed until death or up to 10 years after treatment. A total of 109 complications were observed yielding a crude complication rate of 18% for the whole series. Observed complication rates were 7% in the 16-20 Gy dose range, 19% between 20 and 24 Gy, and 33% in patients receiving more than 24 Gy. Probit analysis of the data indicated a median effective dose (50% complications) of 29 (+/- 0.5) Gy with an estimated standard deviation of 8 Gy. A reasonable estimate of "tolerance" may then be taken as 29 - 8 = 21 Gy. Comparing the 5 anatomical sites revealed no significant differences in estimated tolerance doses. With the available data, no effect of field-size or target volume could be demonstrated. The incidence of complications apparently increases with time in long-term survivors. Although the overall incidence is only 18%, actuarial analysis of the data suggests that the complication rate might have exceeded 50% if all treated patients had survived 10 years. It is concluded that, with the exception of the nervous system and possibly other viscera, a neutron dose of 20 Gy (in 12 fractions over 4 weeks) represents a practical tolerance limit for all sites.

Re-irradiation of locally recurrent tumors with fast neutrons.

Forty-six patients with locally recurrent disease were re-irradiated with fast neutrons at Fermilab. All had received prior radical radiation therapy either with or without surgery. Six were palliative. Forty patients treated with curative intent were analyzed for local response, survival, and complications. The overall response rate was 78% (31/40); 50% (20/40) had a complete local response. Ten of 16 patients (63%) with non-epidermoid carcinomas in the head and neck regions had complete response, whereas only nine of twenty patients (45%) with epidermoid carcinomas were complete responders. In a subset of 12 patients with salivary gland type tumors, 10 had a complete response (83%). Two of these 10 patients are alive beyond 5 years. Observed median survival for the forty patients was 9.3 months, and for complete responders 14.4 months. Observed median survival for partial responders was only 7.5 months. Four of six patients treated for palliation had significant subjective improvement. Significant morbidity, Grade III or greater (EORTC/RTOG scale), was seen in only 10 patients (25%), and this was found to depend directly on the total dose delivered. We conclude that neutron beam therapy can be used as a therapeutic modality for patients with recurrent tumors with an acceptable degree of morbidity.

Failure of accelerated neutron therapy to control high grade astrocytomas.

Sixty-two patients with high grade malignant astrocytoma were treated with fast neutrons using three different treatment schemes to evaluate the effect of shortening the overall time. Dose and fraction number were kept constant. The total dose was 16-18 neutron Gy delivered in six fractions, weekly for 6 weeks, twice a week over 3-4 weeks, or three times a week over 2 weeks. There were no obvious differences in survival times among the three groups. We conclude that accelerated neutron therapy does not improve survival of patients with grade 3 and 4 astrocytoma.

Neutron irradiation of human pelvic tissues yields a steep dose-response function for late sequelae.

PURPOSE: Analysis of the dose-response function in normal tissues following pelvic irradiation for carcinoma of the prostate. METHODS AND MATERIALS: A homogeneous group of 136 patients with locally advanced carcinoma of the prostate were treated with the Fermilab high-energy neutron beam at three dose levels: 19, 20.4, and 21 Gy, using the same treatment plan and fractionation scheme for all patients. RESULTS: Tumor control rates were about 83% at the three dose levels studied. However, the normal tissue complication rate (late sequelae) varied with dose: 0 out of 5 at 19 Gy, 5 out of 58 (8.6%) at 20.4 Gy, and 9 out of 73 (12.3%) at 21 Gy. CONCLUSIONS: Neutron therapy to the pelvis reveals a steep dose-response function for late effects with a coefficient of variation of only 11%. This is lower than that usually observed with photons or with less uniform clinical data sets, and may be characteristic for well-planned high-LET radiotherapy.

Monozygotic twins concordant for late-onset probable Alzheimer disease with suspected Alzheimer disease in four sibs.

Probable Alzheimer disease (AD) is described in 79-year-old male twins with monozygosity confirmed by DNA examination. The first twin to be affected began to show signs of intellectual deterioration at age 70. In the other, onset was at age 72. Four of their living sibs (current age range = 75-92) are also suspected to have AD. The possible roles of genetic and environmental factors in the development of AD in this sibship are discussed.

Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: II. Further cytogenetic analysis of the marker and characterization of the high-level repeat sequences using fluorescence in situ hybridization.

We have further characterized an unusual 22p+ marker chromosome with a double nucleolus organizer region (dNOR) previously identified in a family with late-onset dementia of the Alzheimer type. G-banding and morphology of the marker's q arm were typically normal. However, the p+ arm had a terminal cytological satellite and a GT-positive region at the midpoint. Standard C-banding documented 2 C-positive regions: one was associated with the primary centromere; the other, which was at the midpoint of the p arm, was not associated with a constriction. With replication-banding, there was a darkly staining region in the middle of the p+ arm that resembled the pericentromeric region of a chromosome 21 or 22. Fluorescence in situ hybridization with pXlr 101, a probe recognizing the full repeating unit of rDNA, indicated that the marker had an unusually larger rDNA region; with pU 1.2, a probe recognizing the human rDNA promoter, the signal was a doublet. The marker had 2 signals with a beta-satellite probe, and a second signal in addition to that present at the primary centromere under low stringency with alpha-satellite probes and a classic satellite probe. Immunostaining of chromosome spreads after R-banding and ultraviolet (UV) denaturation showed that the major portion of the marker's p arm was highly methylated.

Microcirculatory studies in erectile disorders.

Local microcirculatory disturbances and fibrosis are thought to contribute to the pathogenesis of erectile dysfunction (ED). The assessment of these disturbances is now possible using non-invasive techniques such as laser Doppler flowmetry (LDF) and measuring transcutaneous pO2 and pCO2. However, these techniques need standardisation (e.g. in terms of equipment, conditions in which the examination is carried out and duration of measurement). Nevertheless, these techniques have a qualitative value. Marked alterations are seen in smokers and hypertensive patients. LDF has also been used to monitor the effect of treatment (e.g. after intracavernosal PGE1). These techniques remain non-diagnostic in individual patients. However, in groups of patients they may produce useful information (e.g. to assess treatments for ED).