ObjectivesAlthough the effect of ultraviolet radiation (UVR) on human skin has been extensively studied, very little is known on how UVR impacts on hair follicle (HF) homeostasis. Here, we investigated how solar spectrum UVR that hits the human skin surface impacts on HF biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.MethodsHuman scalp skin with terminal HFs was irradiated transepidermally ex vivo using either 10 J/cm2 UVA (340–440 nm) + 20 mJ/cm2 UVB (290–320 nm) (low dose) or 50 J/cm2 UVA + 50 mJ/cm2 UVB (high dose) and organ‐cultured under serum‐free conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to UV exposure with 40 J/cm2 UVA + 40 mJ/cm2 UVB and for 3 days after UVR. The effects on various toxicity and vitality read‐out parameters were measured in defined skin and HF compartments.ResultsConsistent with previous results, transepidermal UVR exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low UVA+UVB doses also induced oxidative DNA damage and cytotoxicity in human HFs. In addition, it decreased proliferation and promoted apoptosis of HF outer root sheath (ORS) and hair matrix (HM) keratinocytes, stimulated catagen development, differentially regulated the expression of HF growth factors, and induced perifollicular mast cell degranulation. UVR‐mediated HF damage was more severe after irradiation with high UVR dose and reached also proximal HF compartments. The topical application of 0.1% caffeine did not induce skin or HF cytotoxicity and stimulated the expression of IGF‐1 in the proximal HF ORS. However, it promoted keratinocyte apoptosis in selected HF compartments. Moreover, caffeine provided protection towards UVR‐mediated HF cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential up‐regulation of the catagen‐promoting growth factor.ConclusionOur study highlights the clinical relevance of our scalp UV irradiation ex vivo assay and provides the first evidence that transepidermal UV radiation negatively affects important human HF functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as HF photoprotectants into sun‐protective cosmeceutical and nutraceutical formulations.

In this survey, HIV-positive MSM had significantly different drug use behaviour which may explain the higher HCV burden. However, HCV was also associated with HIV-negative MSM engaging in high-risk sexual practices. All MSM attending sexual health clinics must have a risk assessment and HCV screening should be offered based on the risk. Further studies are warranted to explore the interplay between HCV and HIV risk associated with drug use versus sexual practices.

Reports of sexualised drug taking (chemsex) have increased significantly in recent years. There is currently limited intelligence on chemsex outside of London. An anonymous survey was promoted via several sources including voluntary services and a sexual health clinic in order to establish the risks associated with chemsex, and how support services can best be tailored to meet the needs of those in Greater Manchester, UK. Quantitative and qualitative data were collected on demographics, drug use, sexual practices and barriers and facilitators to accessing support. Fifty-two men who have sex with men completed the online survey. Thirty-nine (75%) were HIV-positive and 11 (21%) were hepatitis C virus (HCV) positive, all of whom were HIV/HCV co-infected. The most commonly used drugs were mephedrone (81%) and gamma hydroxybutyrate/gamma butyrolactone (79%). Nineteen (37%) reported ever injecting drugs. High-risk sexual practices were reported by respondents. Barriers to accessing support included a fear of being recognised. Findings demonstrate those engaging in chemsex are participating in a number of high-risk sexual practices, taking substances with significant risks and administering these substances in potentially high-risk ways. Results demonstrate the need for promotion of existing services, with key areas to target where chemsex sessions are most commonly arranged. Results may be useful in other metropolitan cities, both for commissioning and tailoring of chemsex support services.

Recurrence of mucocutaneous herpes simplex virus (HSV) infections is common in immunosuppressed patients. Thymidine kinase mutations conferring resistance to the antiviral agent aciclovir have been observed in such patients. Recommended second-line therapeutic agents against HSV are associated with significant side effects contributing to disease burden. We present a case of aciclovir-resistant herpes simplex virus 2 (HSV-2) in an immunosuppressed (HIV negative) allogenic peripheral blood stem cell transplant (SCT) recipient which was refractory to second-line therapy. Compassionate acquisition of the novel oral helicase-primase inhibitor pritelivir provided both symptomatic and virological control for the duration of its use. We believe this to be the first clinical use of this therapeutic agent in the United Kingdom

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Blue Gene/L uses a large number of low power processors, together with multiple integrated interconnection networks, to build a supercomputer with low cost, space and power consumption. It uses a novel system software architecture designed with application scalability in mind. However, whether real applications will scale to tens of thousands of processors has been an open question. In this paper, we describe early experience with several applications on a 16,384 node Blue Gene/L system. This study establishes that applications from a broad variety of scientific disciplines can effectively scale to thousands of processors. The results reported in this study represent the highest performance ever demonstrated for most of these applications, and in fact, show effective scaling for the first time ever on thousands of processors.

Recreational drug use (RDU) has been reported to be disproportionately higher in men who have sex with men (MSM) when compared to their heterosexual counterparts. To identify RDU, links to risky sexual practices and infections for MSM attending three sexual health clinics across Manchester, United Kingdom, a retrospective case note review was conducted using a random powered sample of service users attending three sites during 2014. Three hundred and fifty-seven case notes were reviewed across three sites. Eighteen per cent of service users reported any type of RDU. Use of at least one of the three drugs associated with chemsex (crystal methamphetamine, mephedrone, gamma hydroxybutyrate/gamma butyrolactone) was reported by 3.6%. A statistically significant difference was identified between non-drug users and any-drug users reporting: group sex (odds ratio [OR] 5.88, p = 0.013), condomless receptive anal intercourse (CRAI) (OR 2.77, p = 0.003) and condomless oral intercourse (OR 2.52, p = 0.016). A statistically significant difference was identified between chemsex-related drug user and non-drug user groups reporting: group sex (OR 13.05, p = 0.023), CRAI (OR 3.69, p = 0.029) and condomless insertive anal intercourse (OR 1.27, p = 0.039). There was also a statistically higher incidence of gonorrhoea infection in chemsex-related drug use compared with those not using drugs (p = 0.002, OR 6.88). This study identifies that substance use is common in MSM attending sexual health clinics in Manchester. High-risk sexual practices and certain sexually transmitted infections are more common in MSM reporting RDU.

To develop an architecture for information technology service management (ITSM) and design integrated solutions, it is necessary to establish a common understanding of the key conceptual domains involved in delivering IT services-organization, process, tools, and technology-and how they interrelate. This paper presents an integration model for ITSM practitioners. The model is a framework for organizing the assets that constitute an ITSM design. Using this framework, an organization can document the available set of IT services offered and understand how they are composed from finergrained services delivered by internal or external providers. Different service designs are supported, depending on the service requirements and organizational context. This integration model is applicable to both in-house IT organizations and IT service providers, regardless of industry or size of enterprise. It may be used by management software vendors to describe the capabilities of their ITSM offerings and to align those with the needs of different customers, by consultants and integrators to develop engagement materials and solution offerings, and by IT service delivery organizations to document their service designs.