Monitoring the HIV continuum of care in key populations across Europe and Central Asia.

OBJECTIVES: The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. METHODS: Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. RESULTS: Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. CONCLUSIONS: Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities.

HIV continuum of care in Europe and Central Asia.

OBJECTIVES: The European Centre for Disease Prevention and Control (ECDC) supports countries to monitor progress in their response to the HIV epidemic. In line with these monitoring responsibilities, we assess how, and to what extent, the continuum of care is being measured across countries. METHODS: The ECDC sent out questionnaires to 55 countries in Europe and Central Asia in 2014. Nominated country representatives were questioned on how they defined and measured six elements of the continuum. We present our results using three previously described frameworks [breakpoints; Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; diagnosis and treatment quadrant]. RESULTS: Forty countries provided data for at least one element of the continuum. Countries reported most frequently on the number of people diagnosed with HIV infection (37; 93%), and on the number in receipt of antiretroviral therapy (ART) (35; 88%). There was little consensus across countries in their approach to defining linkage to, and retention in, care. The most common breakpoint (>19% reduction between two adjacent elements) related to the estimated number of people living with HIV who were diagnosed (18 of 23; 78%). CONCLUSIONS: We present continuum data from multiple countries that provide both a snapshot of care provision and a baseline against which changes over time in care provision across Europe and Central Asia may be measured. To better inform HIV testing and treatment programmes, standard data collection approaches and definitions across the HIV continuum of care are needed. If countries wish to ensure an unbroken HIV continuum of care, people living with HIV need to be diagnosed promptly, and ART needs to be offered to all those diagnosed.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

A record fuel hot-spot pressure P_{hs}=56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Sharp truth: health care workers remain at risk of bloodborne infection.

BACKGROUND: In 2013, new regulations for the prevention of sharps injuries were introduced in the UK. All health care employers are required to provide the safest possible working environment by preventing or controlling the risk of sharps injuries. AIMS: To analyse data on significant occupational sharps injuries among health care workers in England, Wales and Northern Ireland before the introduction of the 2013 regulations and to assess bloodborne virus seroconversions among health care workers sustaining a blood or body fluid exposure. METHODS: Analysis of 10 years of information on percutaneous and mucocutaneous exposures to blood or other body fluids from source patients infected with a bloodborne virus, collected in England, Wales and Northern Ireland through routine surveillance of health care workers reported for the period 2002-11. RESULTS: A total of 2947 sharps injuries involving a source patient infected with a bloodborne virus were reported by health care workers. Significant sharps injuries were 67% higher in 2011 compared with 2002. Sharps injuries involving an HIV-, hepatitis B virus- or hepatitis C virus (HCV)-infected source patient increased by 107, 69 and 60%, respectively, between 2002 and 2011. During the study period, 14 health care workers acquired HCV following a sharps injury. CONCLUSIONS: Our data show that during a 10-year period prior to the introduction of new regulations in 2013, health care workers were at risk of occupationally acquired bloodborne virus infection. To prevent sharps injuries, health care service employers should adopt safety-engineered devices, institute safe systems of work and promote adherence to standard infection control procedures.

scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints.

With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human interleukin-1-receptor antagonist (hIL-1Ra) or green fluorescent protein was packaged in AAV capsid serotypes 1, 2, 5, 8 and 9. Following infection of human and equine synovial fibroblasts in culture, we found that both were only receptive to transduction with AAV1, 2 and 5. For these serotypes, however, transgene expression from the equine cells was consistently at least 10-fold higher. Analyses of AAV surface receptor molecules and intracellular trafficking of vector genomes implicate enhanced viral uptake by the equine cells. Following delivery of 1 × 10(11) vector genomes of serotypes 2, 5 and 8 into the forelimb joints of the horse, all three enabled hIL-1Ra expression at biologically relevant levels and effectively transduced the same cell types, primarily synovial fibroblasts and, to a lesser degree, chondrocytes in articular cartilage. These results provide optimism that AAV vectors can be effectively adapted for gene delivery to large human joints affected by OA.

Ten-year mortality trends among persons diagnosed with HIV infection in England and Wales in the era of antiretroviral therapy: AIDS remains a silent killer.

OBJECTIVES: We present national trends in death rates and the proportion of deaths attributable to AIDS in the era of effective antiretroviral therapy (ART), and examine risk factors associated with an AIDS-related death. METHODS: Analyses of the national HIV-infected cohort for England and Wales linked to death records from the Office of National Statistics were performed. Annual all-cause mortality rates were calculated by age group and sex for the years 1999-2008 and rates for 2008 were compared with death rates in the general population. Risk factors associated with an AIDS-related death were investigated using a case-control study design. RESULTS: The all-cause mortality rate among persons diagnosed with HIV infection aged 15-59 years fell over the decade: from 217 per 10 000 in 1999 to 82 per 10 000 in 2008, with declines in all age groups and exposure categories except women aged 50-59 years and persons who inject drugs (rate fluctuations in both of these groups were probably a result of small numbers). Compared with the general population (15 per 10 000 in 2008), death rates among persons diagnosed with HIV infection remained high, especially in younger persons (aged 15-29 years) and persons who inject drugs (13 and 20 times higher, respectively). AIDS-related deaths accounted for 43% of all deaths over the decade (24% in 2008). Late diagnosis (CD4 count < 350 cells/µL) was the most important predictor of dying of AIDS [odds ratio (OR) 10.55; 95% confidence interval (CI) 8.22-13.54]. Sixty per cent of all-cause mortality and 81% of all AIDS-related deaths were attributable to late diagnosis. CONCLUSIONS: Despite substantial declines, death rates among persons diagnosed with HIV infection continue to exceed those of the general population in the ART era. Earlier diagnosis could have prevented 1600 AIDS-related deaths over the decade. These findings highlight the need to intensify efforts to offer and recommend an HIV test in a wider range of clinical and community settings.

HIV testing in black Africans living in England.

We examined the uptake of HIV testing in black Africans living in England before the introduction of national testing guidelines. Analyses were conducted using data from an anonymous self-completed questionnaire linked to oral fluid samples to establish HIV status in black Africans attending community venues in England in 2004. Of 946 participants, 44% had ever been tested for HIV and 29% had been tested in the previous 24 months. Of those with undiagnosed HIV, 45% had previously had a negative HIV test. Almost a third of people tested in the UK had been at general practice. Uptake of HIV testing was not associated with perceived risk of HIV. These findings highlight the need for the implementation of national HIV testing guidelines in the UK, including the promotion of testing in general practice. Regular testing in black Africans living in the UK should be promoted regardless of their HIV test history.

Safe travels? HIV transmission among Britons travelling abroad.

OBJECTIVES: The aim of the study was to identify and describe the characteristics of persons born in the UK who acquire HIV infection abroad. METHODS: Analyses using case reports and follow-up data from the national HIV database held at the Health Protection Agency were performed. RESULTS: Fifteen per cent (2066 of 13 891) of UK-born adults diagnosed in England, Wales and Northern Ireland between 2002 and 2010 acquired HIV infection abroad. Thailand (534), the USA (117) and South Africa (108) were the countries most commonly reported. As compared with UK-born adults acquiring HIV infection in the UK, those acquiring HIV infection abroad were significantly (P < 0.01) more likely to have acquired it heterosexually (70% vs. 22%, respectively), to be of older age at diagnosis (median 42 years vs. 36 years, respectively), and to have reported sex with a commercial sex worker (5.6% vs. 1%, respectively). Among men infected in Thailand, 11% reported sex with a commercial sex worker. CONCLUSIONS: A substantial number of UK-born adults are acquiring HIV infection in countries with generalized HIV epidemics, and in common holiday destinations. Of particular concern is the high proportion of men infected reporting sex with a commercial sex worker. We recommend HIV prevention and testing efforts be extended to include travellers abroad, and that sexual health advice be provided routinely in travel health consultations and in occupational health travel advice packs, particularly to those travelling to high HIV prevalence areas and destinations for sex tourism. Safer sex messages should include an awareness of the potential detrimental health and social impacts of the sex industry.

Therapeutic aerosol bioengineering of targeted, inhalable microparticle formulations to treat Mycobacterium tuberculosis (MTb).

Therapeutic aerosol bioengineering (TAB) of Mycobacterium tuberculosis (MTb) therapies using inhalable microparticles offers a unique opportunity to target drugs to the site of infection in the alveolar macrophages, thereby increasing dosing in the lungs and limiting systemic exposure to often toxic drugs. Previous work by us used sophisticated, high content analysis to design the optimal poly(lactide-co-glycolic) acid (PLGA) microparticle for delivery of drugs to alveolar macrophages. Herein, we applied this technology to three different anti-MTb drugs. These formulations were then tested for encapsulation efficiency, drug-release, in vitro killing against MTb and aerosol performance. Methods for encapsulating each of the drugs in the PLGA microparticles were successfully developed and found to be capable of controlling the release of the drug for up to 4 days. The efficacy of each of the encapsulated anti-MTb drugs was maintained and in some cases enhanced post-encapsulation. A method of processing these drug-loaded microparticles for inhalation using standard dry powder inhaler devices was successfully developed that enabled a very high respirable dose of the drug to be delivered from a simple dry powder inhaler device. Overall, TAB offers unique opportunities to more effectively treat MTb with many potential clinical and economic benefits resulting.

Tuberculosis and HIV co-infection in European Union and European Economic Area countries.

In order to ensure the availability of resources for tuberculosis (TB) and HIV management and control, it is imperative that countries monitor and plan for co-infection in order to identify, treat and prevent TB-HIV co-infection, thereby reducing TB burden and increasing the years of healthy life of people living with HIV. A systematic review was undertaken to determine the burden of TB-HIV infection in the European Union (EU) and European Economic Area (EEA). Data on the burden of HIV infection in TB patients and risk factors for TB-HIV co-infection in the EU/EEA were extracted from studies that collected information in 1996 and later, regardless of the year of initiation of data collection, and a narrative synthesis presented. The proportion of HIV-co-infected TB patients varied from 0 to 15%. Western and eastern countries had higher levels and increasing trends of infection over time compared with central EU/EEA countries. Groups at higher risk of TB-HIV co-infection were males, young adults, foreign-born persons, the homeless, injecting drug users and prisoners. Further research is needed into the burden and associated risk factors of co-infection in Europe, to help plan effective control measures. Increased HIV testing of TB patients and targeted and informed strategies for control and prevention could help curb the co-infection epidemic.

The burden of TB-HIV in the EU: how much do we know? A survey of surveillance practices and results.

Information on the burden of tuberculosis (TB)-HIV co-infection is critical for the planning and evaluation of TB-HIV control and treatment strategies. This study assessed current practices in countries of the European Union (EU) and European Economic Area (EEA) for monitoring HIV co-infection in TB surveillance systems, countries' current co-infection burden and associated clinical practice. An online survey was distributed to all national TB surveillance nominated European Centre for Disease Prevention and Control contact points in the EU/EEA. We received 25 responses from 30 countries (83% response rate). Patients' HIV status was collected in 18 out of the 25 TB surveillance systems, usually via clinician reporting (16 out of 18 surveillance systems). Although most countries recommended routine testing of TB patients for HIV, the proportion actually tested varied from 5% to 90%. The burden of HIV co-infection was found to be elevated in countries with higher levels of HIV testing and higher prevalence of HIV. We suggest that TB-HIV co-infection be monitored in all EU/EEA countries to facilitate the planning and evaluation of TB-HIV control strategies. Strengthening collaboration between TB and HIV clinicians and surveillance departments, and consideration of patient confidentiality restraints would be advantageous. The level of HIV testing in TB patients is low despite national recommendations and testing should be further promoted and monitored.

Travel for HIV care in England: a choice or a necessity?

OBJECTIVES: The aims of the study were (1) to measure the distance required to travel, and the distance actually travelled, to HIV services by HIV-infected adults, and (2) to calculate the proportion of patients who travelled beyond local services and identify socio-demographic and clinical predictors of use of non-local services. METHODS: The straight-line distance between a patient's residence and HIV services was determined for HIV-infected patients in England in 2007. 'Local services' were defined as the closest HIV service to a patient's residence and other services within an additional 5 km radius. Multivariable logistic regression was used to identify socio-demographic and clinical predictors of accessing non-local services. RESULTS: In 2007, nearly 57 000 adults with diagnosed HIV infection accessed HIV services in England; 42% lived in the most deprived areas. Overall, 81% of patients lived within 5 km of a service, and 8.7% used their closest HIV service. The median distance to the closest HIV service was 2.5 km [interquartile range (IQR) 1.5-4.2 km] and the median actual distance travelled was 4.8 km (IQR 2.5-9.7 km). A quarter of patients used a 'non-local' service. Patients living in the least deprived areas were twice as likely to use non-local services as those living in the most deprived areas [adjusted odds ratio (AOR) 2.16; 95% confidence interval (CI) 1.98-2.37]. Other predictors for accessing non-local services included living in an urban area (AOR 0.77; 95% CI 0.69-0.85) and being diagnosed more than 12 months (AOR 1.48; 95% CI 1.38-1.59). CONCLUSION: In England, 81% of HIV-infected patients live within 5 km of HIV services and a quarter of HIV-infected adults travel to non-local HIV services. Those living in deprived areas are less likely to travel to non-local services.

Trends over calendar time in antiretroviral treatment success and failure in HIV clinic populations.

OBJECTIVE: Effective antiretroviral therapy (ART) has transformed the care of people with HIV, but it is important to monitor time trends in indicators of treatment success and antic future changes. METHODS: We assessed time trends from 2000 to 2007 in several indicators of treatment success in the UK Collaborative HIV Cohort (CHIC) Study, and using national HIV data from the Health Protection Agency (HPA) we developed a model to project future trends. RESULTS: The proportion of patients on ART with a viral load <50 HIV-1 RNA copies/mL increased from 62% in 2000 to 84% in 2007, and the proportion of all patients with a CD4 count <200 cells/microL decreased from 21% to 10%. During this period, the number of patients who experienced extensive triple class failure (ETCF) rose from 147 (0.9%) to 1771 (3.9%). The number who experienced such ETCF and had a current viral load >50 copies/mL rose fromz 118 (0.7%) to 857 (1.9%). Projections to 2012 suggest sustained high levels of success, with a continued increase in the number of patients who have failed multiple drugs but a relatively stable number of such patients experiencing viral loads >50 copies/mL. Numbers of deaths are projected to remain low. CONCLUSIONS: There have been continued improvements in key indicators of success in patients with HIV from 2000 to 2007. Although the number of patients who have ETCF is projected to rise in the future, the number of such patients with viral loads >50 copies/mL is not projected to increase up to 2012. New drugs may be needed in future to sustain these positive trends.

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance.

OBJECTIVE: The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged > or =13 years. METHODS: A retrospective review of HIV diagnoses reported to well-established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted. RESULTS: Forty-two young people with vertically acquired HIV diagnosed aged > or =13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub-Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13-20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/microL (range, 0-689 cells/microL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis. CONCLUSION: A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age > or =13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV-infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Partial hospitalization: compatible with evidence-based and recovery-oriented treatment?

Partial hospitalization is a service modality that some have suggested is incompatible with both evidence-based and recovery-oriented treatment. The purpose of this study was to examine the accuracy of this assumption. Toward this end, a specific partial hospitalization program was examined using administrative data, self-reports regarding recovery orientation, and fidelity ratings from independent assessors. Findings support that the partial hospitalization program studied has reasonable lengths of stay, provides recovery-oriented services, and has implemented evidence-based practices. We conclude that partial hospitalization programs have the potential to become part of an evidence-based and recovery-oriented system.

Could male circumcision reduce HIV incidence in the UK?

We consider the public health relevance of three recent African clinical trials showing male circumcision (MC) to reduce female-to-male transmission of HIV for the UK. Although heterosexually acquired HIV infections now account for the majority of new diagnoses in the UK each year, it is important to note that when considering the public health relevance of MC for the UK a large majority of these infections are acquired abroad. Men who have sex with men (MSM) remain those most at risk of acquiring their HIV infection in the UK. The efficacy and effectiveness of MC among MSM and in particular its protective role in unprotected anal intercourse between men remains unknown. Any future consideration of the role of MC in reducing HIV incidence in the UK should not be at the expense of weakening existing effective interventions.

Situation of HIV infections and STIs in the United Kingdom in 2007.

In the United Kingdom (UK) in 2007, an estimated 77,400 persons were living with human immunodeficiency virus (HIV) of whom 28% are unaware of their infection. A total of 7,734 persons were newly diagnosed with HIV infection in 2007, of which 31% were diagnosed late. This highlights the need for wider HIV testing, especially in those areas with a high diagnosed prevalence, as recommended in recent national guidelines. Among newly diagnosed cases of HIV in 2007, 41% acquired their infection through sex between men (four in five of whom acquired their infection in the UK) and 55% through heterosexual contact (four in five of whom acquired their infection abroad, mainly in sub-Saharan Africa). Young persons aged 16 to 24 years are disproportionally affected by sexually transmitted diseases (STIs) accounting for 65% of genital chlamydia infections, 50% of cases of genital warts and 50% of cases of gonorrhoea that were diagnosed in 2007.

Appraisal, assessment and career development for doctors in training: the Mersey Deanery personal development portfolio.

OBJECTIVES: To develop a robust valid and exportable appraisal and assessment process for doctors in training which is portfolio based and works at all hospitals within the deanery. It is called the personal development portfolio. DESIGN: For every senior house officer, there was a recorded meeting with his or her supervisor, at the beginning, midterm and at the end of the post. An outside assessor witnessed the exit assessment meeting. SETTING: The Wirral Hospital, a District General Hospital with 72 senior house officers in 10 different specialties was used as a pilot site to develop the process. Then the process was exported and implemented at the other 12 trusts of the deanery. MAIN OUTCOME MEASURES: Records were kept of the induction, midterm and exit assessment meetings. A record was kept of the number of senior house officers succeeding and failing at their exit assessments. Also, the number promoted to the specialist registrar grade was recorded. RESULTS: The process was performed every 6 months on 11 occasions between 2000 and 2005. It involved 72 senior house officers in 10 different specialties. On each occasion, participation usually exceeded 70%: 623 were appraised and assessed and 609 of them (97.8%) had satisfactory exit assessments. For 14 doctors (2.2%), the process identified a cause for concern, which was usually accepted by the doctor and sometimes allowed remedial action to be taken. Twenty-six (4.2%) were promoted to the specialist registrar grade in this period. The process also identified the strengths and weaknesses of the senior house officer posts in the 10 different specialties that had such posts, and was used to encourage good medical teaching practice in them. Over 4 years, we exported the process to all the other 12 Trusts in the Mersey Deanery. Once established, the process was easy to use for both trainees and trainers, although it was time consuming. CONCLUSIONS: It was possible to develop and implement a portfolio based appraisal and assessment process, which was accepted by senior house officers and their trainers in all specialties at all hospitals within the deanery. Now that the senior house officer grade has been superseded by the Foundation and the training grade years, the principles of the personal development portfolio are being used to appraise and assess doctors in these grades too.

Impact of the duration of control of cattle lice with eprinomectin on leather quality.

The relationship between lice infestation in calves during their first winter and damage to the leather produced was investigated in a trial involving 500 calves, 100 of which were treated with a pour-on endectocide during the first winter. All the calves received routine lice treatment in the second winter and were reared to slaughter weight. The hides were removed at the abattoir, tanned, inspected for lice-related damage, and graded according to their suitability for the production of high quality leather. The untreated group developed natural infestations of the chewing louse (Bovicola bovis) during the first winter but none was observed in the second winter. Hides from cattle infested with lice in their first winter had higher levels of lice damage than hides from those treated with eprinomectin, at both the chrome-tanned and dried dyed-crust stages of leather production.