Interferon as a macrophage activating factor. I. Enhancement of cytotoxicity by fresh and matured human monocytes in the absence of other soluble signals

The cytolytic activity ofhuman peripheral blood monocytes in vitro against K-562 human leukaemic target cells was stimulated by human fibroblast (fi-) and leucocyte (a-) interferon (IFN). Stimulation was by up to several times the corresponding control activity, and was observed with freshly isolated monocytes, and with monocytes cultured for various periods up to 10 days. The cytolytic activity of untreated monocytes was detectable at very low effector: target ratios ( < 5: 1), and fell between days 1 and 4 in culture, normally rising again towards the initial activity at day 8; this pattern was also observed when IFN was present continuously, although the activities were then always higher than in the corresponding control cells. Cytolysis showed a lag of about 6 hr, in contrast to that by natural killer (NK) cells, and was routinely measured over 24 hr. The course of stimulation by IFN and its dose-response were studied. Stimulation required the presence of IFN for at least 24 hr, and was maximal with between 1,000 and 10,000 units of IFN/ml. When IFN containing media were removed and replaced with control media, the monocyte activity remained stimulated for at least 4 days. Stimulation by fl-IFN was blocked by a specific antibody to fl-IFN, under conditions in which assayable IFN activity was also neutralized. Several control experiments indicated that the action of IFN was on the monocytes and not on the target cells. The morphological maturation of monocytes was retarded by IFN, even in cultures containing up to 50% serum. The effectiveness of fibroblast IFN indicated that stimulation could not be attributed to the lymphokines which might contaminate a-IFN. The action of IFN did not require simultaneous or antecedent in vitro stimulation by endotoxin. This was indicated both by serum free experiments, and also by others in which polymixin B was used to complex with and render unavailable any endotoxin present. Endotoxin showed an independent stimulatory effect, which could be prevented by polymixin

Buprenorphine added on brief cognitive behavioral therapy for treatment of methamphetamine use disorder

Background: Methamphetamine (MA) use remains a major public health concern around the world. Recent findings suggest that buprenorphine may be helpful for cocaine use reduction. Moreover, animal studies described reduced dopamine peak effect following MA use, due to the administration of low dose buprenorphine. Objectives: This study examined the effectiveness of buprenorphine with brief cognitive behavioral therapy on MA use disorder. Methods: The study was conducted in an outpatient substance abuse treatment center in Qazvin, Iran. Nineteen MA users received buprenorphine for 24 weeks combined with brief cognitive behavioral therapy in an outpatient substance abuse treatment program, three times per week, as a before and after non - randomization study. Clinical outcomes included treatment retention, MA use, degree of MA dependency and craving, quality of life, cognitive abilities questionnaire, addiction severity and also adverse events. Data was analyzed by performing repeated measures analysis and the Friedman test for nonparametric variables. Results: Fifteen participants completed the study during six months and frequency of MA use was significantly decreased at 24 weeks (P &lt; 0.001). There were also significant reductions in craving (P &lt; 0.001), degree of MA dependence (P &lt; 0.001), and improvements in quality of life, cognitive ability, and some subscales of addiction severity. Conclusions: The results of this preliminary clinical study demonstrated that buprenorphine could potentially attenuate MA craving and alternate rewarding effects of MA and had promising effects on cognitive impairment. Furthermore, buprenorphine can be considered as a harm reduction intervention in some communities, in which the people, as a result of cultural beliefs, do not accept a therapy, which only consists of counseling and no medications

Design and Characterization of 1.8-3.2 THz Schottky-based Harmonic Mixers

A room-temperature Schottky diode-based WM-86 (WR-0.34) harmonic mixer was developed to build high-resolution spectrometers, and multi-pixel receivers in the THz region for applications such as radio astronomy, plasma diagnostics, and remote sensing. The mixer consists of a quartz-based Local Oscillator (LO), Intermediate-Frequency (IF) circuits, and a GaAs-based beam-lead THz circuit with an integrated diode. Measurements of the harmonic mixer were performed using a 2 THz solid-state source and 2.6906 THz QCL. A conversion loss of 27 dB for the 3rd harmonic mixing and a conversion loss of 30 dB for the 4th harmonic mixing was achieved. This is the first development of a wideband WM-86 (WR-0.34) harmonic mixer with planar Schottky diode integrated on a beam-lead THz circuit that uses a lower LO harmonic factor for 1.8-3.2 THz RF frequency. Furthermore, this result represents the best Schottky-based mixer in this frequency range

Quitting patient care and career break intentions among general practitioners in South West England: findings of a census survey of general practitioners

Objective: Given recent concerns regarding general practitioner (GP) workforce capacity, we aimed to describe GPs’ career intentions, especially those which might impact on GP workforce availability over the next 5 years. Design: Census survey, conducted between April and June 2016 using postal and online responses , of all GPs on the National Health Service performers list and eligible to practise in primary care. Two reminders were used as necessary. Setting: South West England (population 3.5  million), a region with low overall socioeconomic deprivation. Participants: Eligible GPs were 2248 out of 3370 (67 % response rate). Main outcome measures: Reported likelihood of permanently leaving or reducing hours spent in direct patient care or of taking a career break within the next 5 years and present morale weighted for non-response. Results: Responders included 217 7 GPs engaged in patient care. Of these, 863 (37% weighted, 95%  CI 35 % to 39 %) reported a high likelihood of quitting direct patient care within the next 5 years. Overall, 1535 (70% weighted, 95%  CI 68 % to 72 %) respondents reported a career intention that would negatively impact GP workforce capacity over the next 5 years, through permanently leaving or reducing hours spent in direct patient care, or through taking a career break. GP age was an important predictor of career intentions; sharp increases in the proportion of GPs intending to quit patient care were evident from 52 years. Only 305 (14% weighted, 95%  CI 13 % to 16 %) reported high morale, while 1195 ( 54 % weighted, 95%  CI 52 % to 56 %) reported low morale. Low morale was particularly common among GP partners. Current morale strongly predicted GPs’ career intentions; those with very low morale were particularly likely to report intentions to quit patient care or to take a career break. Conclusions: A substantial majority of GPs in South West England report low morale. Many are considering career intentions which, if implemented, would adversely impact GP workforce capacity within a short time period. Study registration: NIHR HS&DR - 14/196/02, UKCRN ID 20700

Wolbachia Induces Male-Specific Mortality in the Mosquito Culex pipiens (LIN Strain)

Background: Wolbachia are maternally inherited endosymbionts that infect a diverse range of invertebrates, including insects, arachnids, crustaceans and filarial nematodes. Wolbachia are responsible for causing diverse reproductive alterations in their invertebrate hosts that maximize their transmission to the next generation. Evolutionary theory suggests that due to maternal inheritance, Wolbachia should evolve toward mutualism in infected females, but strict maternal inheritance means there is no corresponding force to select for Wolbachia strains that are mutualistic in males. Methodology/Principal findings: Using cohort life-table analysis, we demonstrate that in the mosquito Culex pipiens (LIN strain), Wolbachia-infected females show no fitness costs due to infection. However, Wolbachia induces up to a 30% reduction in male lifespan. Conclusions/significance: These results indicate that the Wolbachia infection of the Culex pipiens LIN strain is virulent in a sex-specific manner. Under laboratory situations where mosquitoes generally mate at young ages, Wolbachia strains that reduce male survival could evolve by drift because increased mortality in older males is not a significant selective force

A methodology for obtaining plasticity characteristics of metallic coatings via instrumented indentation

A methodology is presented for inferring the yield stress and work-hardening characteristics of metallic coatings from indentation data. It involves iterative use of FEM modelling, with predicted outcomes (load-displacement relationships and residual indent shapes) being systematically compared with experimental data. The cases being considered are ones in which the indenter penetration depth is a significant fraction of the coating thickness, so that the properties of the substrate, and possibly of the interface, are of significance. The methodology is thus suitable for the testing of thin coatings. In the present work, the coatings were in fact relatively thick (hundreds of microns) and the (spherical) indenter penetration was a substantial fraction of this. In this way, the basic validity of the methodology could be investigated with minimal complications from effects related to microstructure, oxide films, surface roughness etc. Furthermore, the properties of both coating and substrate (in the through-thickness direction) were established separately via conventional compression testing. The systems studied were copper (yield stress ~15 MPa) on stainless steel (yield stress ~350 MPa) and vice versa. Both exhibited significant work hardening. It is concluded that the methodology is basically reliable, with relatively good sensitivity and resolution, although this does depend on several factors, which are highlighted in the paper. It is unlikely to be suitable for very thin (sub-micron) films, but should be reasonably accurate for coatings of thickness down to a few microns.This work has been supported by EPSRC (grant RG62695) and also by AWE, as part of an ongoing collaboration aimed at the development of robust and user-friendly tools for the extraction of mechanical property characteristics from instrumented indentation data.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ijsolstr.2015.10.029 In compliance with current EPSRC requirements, the input data for the indentation modeling described in this paper, including meshing and boundary condition specifications, are available at the following URL: www.ccg.msm.cam.ac.uk/publications/resources. These files can be downloaded and used in ABAQUS FEM models. Data supplied are for a representative case (with a spherical indenter and radial symmetry)

Understanding why primary care doctors leave direct patient care: a systematic review of qualitative research

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: All data relevant to the study are included in the article or uploaded as supplementary information. No additional data available.Background UK general practitioners (GPs) are leaving direct patient care in significant numbers. We undertook a systematic review of qualitative research to identify factors affecting GPs’ leaving behaviour in the workforce as part of a wider mixed methods study (ReGROUP). Objective To identify factors that affect GPs’ decisions to leave direct patient care. Methods Qualitative interview-based studies were identified and their quality was assessed. A thematic analysis was performed and an explanatory model was constructed providing an overview of factors affecting UK GPs. Non-UK studies were considered separately. Results Six UK interview-based studies and one Australian interview-based study were identified. Three central dynamics that are key to understanding UK GP leaving behaviour were identified: factors associated with low job satisfaction, high job satisfaction and those linked to the doctor–patient relationship. The importance of contextual influence on job satisfaction emerged. GPs with high job satisfaction described feeling supported by good practice relationships, while GPs with poor job satisfaction described feeling overworked and unsupported with negatively impacted doctor–patient relationships. Conclusions Many GPs report that job satisfaction directly relates to the quality of the doctor–patient relationship. Combined with changing relationships with patients and interfaces with secondary care, and the gradual sense of loss of autonomy within the workplace, many GPs report a reduction in job satisfaction. Once job satisfaction has become negatively impacted, the combined pressure of increased patient demand and workload, together with other stress factors, has left many feeling unsupported and vulnerable to burn-out and ill health, and ultimately to the decision to leave general practice

A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: a cross sectional study comparing Osgood Schlatter disease with controls

Background Osgood–Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. Purpose This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. Study Design Cross-sectional study. Methods Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). Results Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2). Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, −0.05, 95% CI: −0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, −0.09, 95% CI: −0.4 to 0.2, p = 0.04; distal mean difference, −0.6, 95% CI: −0.9 to −0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = −2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. Conclusion Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. Clinical Relevance Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD

Using interpretative phenomenological analysis to inform physiotherapy practice: An introduction with reference to the lived experience of cerebellar ataxia

The attached file is a pre-published version of the full and final paper which can be found at the link below.This article has been made available through the Brunel Open Access Publishing Fund.Qualitative research methods that focus on the lived experience of people with health conditions are relatively underutilised in physiotherapy research. This article aims to introduce interpretative phenomenological analysis (IPA), a research methodology oriented toward exploring and understanding the experience of a particular phenomenon (e.g., living with spinal cord injury or chronic pain, or being the carer of someone with a particular health condition). Researchers using IPA try to find out how people make sense of their experiences and the meanings they attach to them. The findings from IPA research are highly nuanced and offer a fine grained understanding that can be used to contextualise existing quantitative research, to inform understanding of novel or underresearched topics or, in their own right, to provoke a reappraisal of what is considered known about a specified phenomenon. We advocate IPA as a useful and accessible approach to qualitative research that can be used in the clinical setting to inform physiotherapy practice and the development of services from the perspective of individuals with particular health conditions.This article is available through the Brunel Open Access Publishing Fund

Phase Locking Of A 2.5 THz Quantum Cascade Laser To A Microwave Reference Using THz Schottky Mixer

The frequency of a 2.5 THz QCL are stabilized to sub-hertz accuracy by phase-locking to a stable 100 MHz microwave reference, using a 2.3–3.2 THz room temperature Schottky diode based harmonic mixer. The down-converted phase locked beat note is stable over a long term test