Associations with sub-optimal clinic attendance and reasons for missed appointments among heterosexual women and men living with HIV in London.

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.

The association between use of chemsex drugs and HIV clinic attendance among gay and bisexual men living with HIV in London.

OBJECTIVES: To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London. METHODS: A cross-sectional survey of adults (> 18 years) diagnosed with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015). Participants self-completed an anonymous questionnaire linked to clinical data. Sub-optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non-attendance for > 1 year. RESULTS: Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub-optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub-optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub-optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10-2.65, P = 0.02). CONCLUSIONS: Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men.

COVID-19 restrictions and recreational fisheries in Ontario, Canada: Preliminary insights from an online angler survey.

The COVID-19 pandemic and corresponding public health mitigation strategies have altered many facets of human life. And yet, little is known about how public health measures have impacted complex socio-ecological systems such as recreational fisheries. Using an online snowball survey, we targeted resident anglers in Ontario, Canada, to obtain preliminary insights on how the pandemic has impacted recreational fishing and related activity. We also explored angler perspectives on pandemic-related restrictions and other aspects of fisheries management. Our results point to the value of recreational fisheries for the mental and physical well-being of participants, as well as the value and popularity of outdoor recreation during a pandemic. Although angling effort and fish consumption appeared to decline during the early phases of the pandemic, approximately 21 % of the anglers who responded to our survey self-identified as new entrants who had begun or resumed fishing in that time. Self-reported motivations to fish during the pandemic suggest that free time, importance to mental and physical health, and desires for self-sufficiency caused some anglers to fish more, whereas a lack of free time, poor or uncertain accessibility, and perceived risks caused some anglers to fish less. Respondents also expressed their desires for more clear and consistent communication about COVID-19 fishing restrictions from governments, and viewed angling as a safe pandemic activity. Information on recreational angler behaviours, motivations, and perspectives during the pandemic may prove valuable to fisheries managers and policy makers looking to optimize their strategies for confronting this and other similar crises.

Development and application of a new measure of engagement in out-patient HIV care.

OBJECTIVES: Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. METHODS: We conducted semi-structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow-up as "in care" (on or before the time of the next expected attendance) or "out of care" (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. RESULTS: The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person-months were "in care". Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. CONCLUSIONS: This algorithm describing engagement in HIV care incorporates a time-updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.

Building an Opt-Out Model for Service-Level Consent in the Context of New Data Regulations.

The General Data Protection Regulation (GDPR) was introduced in 2018 to harmonize data privacy and security laws across the European Union (EU). It applies to any organization collecting personal data in the EU. To date, service-level consent has been used as a proportionate approach for clinical trials, which implement low-risk, routine, service-wide interventions for which individual consent is considered inappropriate. In the context of public health research, GDPR now requires that individuals have the option to choose whether their data may be used for research, which presents a challenge when consent has been given by the clinical service and not by individual service users. We report here on development of a pragmatic opt-out solution to this consent paradox in the context of a partner notification intervention trial in sexual health clinics in the UK. Our approach supports the individual's right to withhold their data from trial analysis while routinely offering the same care to all patients.

Active Precipitation of Radiation Belt Electrons Using Rocket Exhaust Driven Amplification (REDA) of Man-Made Whistlers.

Ground-based very low frequency (VLF) transmitters located around the world generate signals that leak through the bottom side of the ionosphere in the form of whistler mode waves. Wave and particle measurements on satellites have observed that these man-made VLF waves can be strong enough to scatter trapped energetic electrons into low pitch angle orbits, causing loss by absorption in the lower atmosphere. This precipitation loss process is greatly enhanced by intentional amplification of the whistler waves using a newly discovered process called rocket exhaust driven amplification (REDA). Satellite measurements of REDA have shown between 30 and 50 dB intensification of VLF waves in space using a 60 s burn of the 150 g/s thruster on the Cygnus satellite that services the International Space Station. This controlled amplification process is adequate to deplete the energetic particle population on the affected field lines in a few minutes rather than the multi-day period it would take naturally. Numerical simulations of the pitch angle diffusion for radiation belt particles use the UCLA quasi-linear Fokker Planck model to assess the impact of REDA on radiation belt remediation of newly injected energetic electrons. The simulated precipitation fluxes of energetic electrons are applied to models of D-region electron density and bremsstrahlung X-rays for predictions of the modified environment that can be observed with satellite and ground-based sensors.

Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation.

Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products.

Microsuction aural toilet in ENT outpatients: a questionnaire to evaluate the patient experience.

Microsuction toilet of debris from the ear canal is a commonly performed procedure within the ENT outpatient clinic. This department has received two complaints from patients following microsuction aural toilet over the past year. These cases will be discussed. We wish to assess the frequency of side effects following aural microsuction in our department. A prospective questionnaire studied 164 patients undergoing aural microsuction over a 3 month period. From the total of 164 patients surveyed, only 74 (45%) did not report any adverse effects. Patients with mastoid cavities reported higher levels of vertigo when compared to those with normal ears (p < 0.001). A high proportion of patients have reported adverse side effects following aural microsuction. Medical staff should also be aware that certain patient subgroups are more prone to adverse effects. It would be appropriate to ensure that patients are counselled before suction takes place.

RETRACTED: IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas.

This article has been retracted at the request of the Editor-in-Chief due to concerns regarding the legitimacy of images and data presented in the paper. Though a corrigendum (Can. Lett. Vol. 469, 2020, pages 524-535) was previously published to address some of these concerns, this corrigendum has also been found to contain errors and therefore cannot stand. Specific concerns are listed below. The Editor and Publisher received a letter from the University of Portsmouth alerting us to an investigation into alleged research misconduct. The University concluded their investigation with external experts and determined that misconduct did take place in relation to the research involved in this paper. Upon our separate investigation, it has been determined that the paper headline relies on showing that there was considerable reduction of IGF1R, IL6R and EGFR post treatment in all cell lines. During review, it was determined that this cannot be concluded from the presented data. For example, in SEBTA-003 the EGFR levels go up and there is no difference in IGFR1. It is apparent from Fig 4d that in the SEBTA-003 cell line the EGFR level does not go down, which is stated in the Results section on page 32, it is rather going up. The data for IGFR1 are inconclusive and there are concerns regarding the blot. The general implications would be that the effects of the drug IP1867B does not seem to be the same for all tested cell lines, and this should have been discussed in detail by the authors. Additionally, in subsequent experiments (Fig. 4g and h) the SEBTA-003 cell line (no reduction of EGFR, rather increased expression) and the other 3 cell lines (reduction of EGFR) show similar responses. This is particularly evident in Fig. 4g: Two cell lines are compared, SEBTA-003 (increased EGFR expression) and UP-029 (decreased EGFR expression), both behave similarly after exposure to drugs. The corrigendum (https://doi.org/10.1016/j.canlet.2019.10.002) issue is with respect to the Supplemental Figure 6i EGFR, particularly panel IP1867B. The Corrigendum states that the left part is a cut out of the very right part. If so, the bands for IP1867B should show the same staining pattern - but they do not. Also, in the Corrigendum, there are incorrect mentions between day 14 in the Figure and day 19 in the Figure legend. All authors were informed of the retraction in advance. Drs. Pritchard and Duckworth agreed to the retraction. The corresponding author, Dr Hill, did not agree to the retraction. No response had been received from Drs. Mihajluk, Simms, Reay, Madureira, Howarth, Murray, Nasser and Pilkinton at the time of the retraction being published.

Ageing and the auditory system.

There are a number of pathophysiological processes underlying age related changes in the auditory system. The effects of hearing loss can have consequences beyond the immediate loss of hearing, and may have profound effects on the functioning of the person. While a deficit in hearing can be corrected to some degree by a hearing aid, auditory rehabilitation requires much more than simply amplifying external sound. It is important that those dealing with elderly people are aware of all the issues involved in age related hearing loss.

The inflammatory response of rabbit skin to topical arachidonic acid and its pharmacological modulation.

The inflammatory reaction induced by the intradermal injection of arachidonic acid into the rabbit dermis has been investigated. Plasma extravasation was measured by the leakage of 125I-albumin into the tissues and polymorphonuclear leukocyte (PMNL) accumulation was assessed histologically. Arachidonic, 5,8,11,14,17-eicosapentaenoic and 8,11,14-eicosatrienoic acids, but not oleic, linoleic or linolenic acids, caused a concentration-related plasma extravasation following their intra-dermal injection. The plasma extravasation induced by arachidonic acid was dependent on PMNLs. PMNL infiltration and plasma extravasation into arachidonic acid-injected skin sites was inhibited by the mixed cyclo-oxygenase-lipoxygenase inhibitor, BW755C. Arachidonic acid-induced plasma extravasation was inhibited by cyclo-oxygenase and 5-lipoxygenase inhibitors but not by the Paf antagonist, kadsurenone. The inflammation induced by arachidonic acid in the rabbit dermis may be a useful model for evaluating 5-lipoxygenase inhibitors which could be potentially useful anti-inflammatory agents for the treatment of psoriasis and other inflammatory diseases.

Leukocyte recruitment in the subcutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B1.

The subcutaneous sponge implant model of acute inflammation in the rat has been evaluated as a suitable test system for evaluating the potential anti-inflammatory efficacy of 5-lipoxygenase inhibitors. The inflammatory parameters measured were exudate volume and leukocyte recruitment. Specific radioimmunoassays were used to measure (1) 5-lipoxygenase (LPO) and cyclo-oxygenase (CO) activity in exudate leukocytes stimulated ex vivo with A23187, and (2) the LTB4 and PGE2 content of inflammatory exudate. The NSAIDs flurbiprofen and indomethacin inhibited cell recruitment, exudate volume and CO activity with ED50S of approximately 1 mg per kg p.o. but failed to inhibit LPO activity at 10 mg per kg p.o. Nafazatrom (Bayer 6575), quercetin and NDGA, which inhibit LPO activity in vitro, were inactive against all parameters when dosed at 100 mg per kg p.o. The "mixed inhibitors" BW755C and phenidone were approximately equipotent inhibitors of LPO activity but BW755C was 10 times more potent than phenidone against CO activity. BW755C was also greater than 10 times more potent at inhibiting cell recruitment and exudate volume than phenidone suggesting that the anti-inflammatory efficacy of the mixed inhibitors reflect their potency against CO rather than LPO activity. Time course studies demonstrated that the inhibitor effects of BW755C and phenidone on leukocyte recruitment reflected a reduction in the PGE2 but not the LTB4 content of the inflammatory exudate. Polyester sponges soaked in high concentrations of LTB4 caused only a modest (2-fold) increase in leukocyte recruitment whilst physiological levels were inactive. The results taken together suggest that CO products make a major contribution to leukocyte recruitment in this model whilst the LPO product LTB4 has little role. This model therefore is of little value for evaluating the anti-inflammatory efficacy of 5-lipoxygenase inhibitors. Moreover, the rat would appear to be unsuitable for evaluating the role of LTB4 in acute inflammation.

Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS.

The immunofluorescent distribution of ZO-1, a tight junction-associated protein, was studied in murine circumventricular organs. These regions generally express a less restrictive blood-brain barrier than is found in other areas of the CNS. In the remaining brain parenchyma, where a characteristic blood-brain barrier exists, ZO-1 was localized in discrete, continuous lines along blood vessels, presumably in association with endothelial cell tight junctions. The ependymal cells in the ventricular walls displayed a more punctate pattern of ZO-1 distribution, indicative of discontinuous tight junctions. In two of the circumventricular organs examined, the median eminence and the subfornical organ, many capillaries lacked detectable ZO-1 immunoreactivity while the apical aspects of the specialized ependymal cells (tanycytes) revealed an unbroken ZO-1 distribution. Scant labelling of ZO-1 in blood vessels was found in the area postrema, and only weak and discontinuous ZO-1 labelling was present in the ventricular wall. Capillaries of the organum vasculosum laminae terminalis expressed ZO-1 immunoreactivity which was comparable to the pattern observed in CNS regions with typical blood-brain barrier. The subcommissural organ, known to contain a blood-brain barrier, also displayed continuous ZO-1 staining in blood vessels. Unbroken ZO-1 distribution was observed in the specialized ependymal cells adjacent to both the organum vasculosum laminae terminalis and subcommissural organ. These immunocytochemical data demonstrate a distribution of ZO-1 in CNS parenchyma outside the circumventricular organs that is consistent with an organization of tight junctions which prevent free paracellular exchange of substances between blood and neuropil but which allow for continuity between CSF and the neuronal environment. The ZO-1 staining pattern in blood vessels and ventricular walls of the circumventricular organs is heterogeneous despite the prevalent absence of a functional blood-brain barrier.

Biochemical indices of osteomalacia in pregnant Asian immigrants in Britain.

Serum calcium, phosphate and alkaline phosphatase, and urinary calcium excretion were examined during the second trimester of uncomplicated normal pregnancy in Asian immigrants to Britain and in local Caucasians. The mean serum calcium was significantly lower in Asians than in Caucasians, and the mean serum alkaline phosphatase was significantly higher in Asians. The geometric mean of the urinary calcium excretion was highly significantly lower in Asians than in Caucasians. The variances of the serum calcium, serum alkaline phosphatase, and urine calcium excretion did not differ significantly in the two populations. This indicates that there is a shift in values of immigrant Asians as a group compared with Caucasians. A comparison with figures obtained on normal nonpregnant persons of both suggests that the shift is not an inherent feature of the Asian population.

The Leeds regional quality control scheme for clinical biochemistry: a progress report.

The results from a regional quality control scheme for clinical biochemistry are analysed. Comparison with results from an earlier period shows that the quality of several of the 15 routine analyses has improved. The methods by which the sera are produced and distributed, and the weekly results are analysed, are described. Each of the 25 laboratories receives an individual weekly computer printout within 24 hours of the deadline for the receipt of results. At the end of each six-month period a printout is produced ranking each laboratory for ;accuracy' and ;precision' for each test.

Method for rapid isolation and analysis of algal virus DNA.

A quick method has been developed for isolating viral DNA from small cultures of eukaryotic algae infected with PBCV-1 or similar viruses. The DNA preparations are virtually free of contaminating host DNA and are suitable substrates for restriction enzymes. 5 ml cultures yield 8-25 micrograms of viral DNA. Many plaque-purified isolates from environmental water samples can be analyzed in a day.

Intrathecal fibrinolytic therapy after subarachnoid hemorrhage: dosage study in a primate model and review of the literature.

Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currently investigating intrathecal thrombolytic therapy with human, recombinant, tissue plasminogen activator (rt-PA) in a primate model of subarachnoid hemorrhage (SAH) and cerebral vasospasm (VSP). In the present study 16 monkeys were divided into 4 groups of 4, and each group received a different dose of sustained-release gel rt-PA at the time of experimental SAH. Cerebral angiography seven days later showed that whereas no VSP occurred in the groups receiving 0.5 or 0.75 mg of rt-PA, mild to moderate VSP occurred in the groups receiving 0.125 or 0.25 mg of rt-PA. Analysis of the combined 2 smaller dosage groups revealed significant (P less than 0.05) reduction of lumen caliber in the clot-side internal carotid (C3 and C4), proximal anterior cerebral (A1) and middle cerebral (MCA) arteries. Gross subarachnoid clot remained in all of the animals in the 0.125 and 0.25 mg dose groups, in 2 of the animals in the 0.5 mg dose group, and none of the animals in the 0.75 mg dose group. It was concluded that 0.75 mg of gel rt-PA is sufficient to completely lyse a 4.25 ml SAH and prevent VSP in our primate model. The literature on fibrinolysis and erythrocyte clearance in cerebrospinal fluid (CSF) is reviewed.