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We present an experimental and theoretical study for the lattice vibrational (phonon) modes in the quasi-one-dimensional (or chain-like) antiferromagnet RbCoCl3 at low temperatures both above and below the two different magnetic phase transitions. Clear evidence is found for the role of spin-phonon interactions in providing a temperature-dependent contribution for the frequencies of the E1g and E2g symmetry phonons that occur with frequencies comparable to those of the spin wave excitations (magnons) in this compound. The behaviour in RbCoCl3, as studied here by Raman scattering experiments, is quite different from that typically observed in rutile-structure antiferromagnets where the spin-phonon coupling has been well characterized. The theory is modified to take account of the strong Ising-like component in the spin Hamiltonian. This enables the spin-phonon coupling parameters to be deduced, with the analysis also revealing the onset of an extra frequency shift for the phonons below the transition temperature TN1 = 28 K associated with magnetic ordering along the Co chains.

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METHODS AND PRINCIPAL FINDINGS: A retrospective study of imported VL to the HTD, London including patients diagnosed and/or managed at the HTD between January 1995 and July 2013. We analyse patient demographics, risk factors for developing VL, diagnosis, investigation, management and outcome. Twenty-eight patients were treated for VL at the HTD over an 18 year period. The median age at VL diagnosis was 44 years (range 4-87 years) with a male to female ratio of 2:1. Most patients were British and acquired their infection in the Mediterranean basin. The median time from first symptom to diagnosis was six months with a range of 1-12 months and diagnosis included microscopic visualisation of leishmania amastigotes, positive serological tests (DAT and k39 antibody) or identification of leishmania DNA. Nineteen patients had some form of immunocompromise and this has increased proportionally compared to previously described data. Within the immunocompromised group, the ratio of those with autoimmune disease has increased. Immunocompromised patients had lower cure and higher relapse rates. CONCLUSIONS: The rise of VL in patients with immunocompromise secondary to autoimmune disease on immunomodulatory drugs presents new diagnostic and therapeutic challenges. VL should be a differential diagnosis in immunocompromised patients with pyrexia of unknown origin returning from travel in leishmania endemic areas.

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Leprosy (or Hansen's disease) is a curable chronic infectious disease caused by the acid-fast bacillus Mycobacterium leprae. While leprosy remains one of the most common causes of neuropathy worldwide, its rarity in the UK means that many doctors are unfamiliar with the typical clinical features. This is problematic because early recognition and treatment is vital in order to minimise disease-related complications such as nerve injury. We describe a 75-year-old man who presented with multiple mononeuropathy (mononeuritis multiplex, particularly affecting the ulnar nerves) and typical granulomatous skin lesions, in whom the diagnosis was made on the basis of skin biopsy. We highlight the clinical features, investigations and treatment of the patient, and provide information about the epidemiology and pathogenesis of leprosy.

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Selective growth and self-organization of silicon-germanium (SiGe) nanowires (NWs) on focused ion beam (FIB) patterned Si(111) substrates is reported. In its first step, the process involves the selective synthesis of Au catalysts in SiO2-free areas; its second step involves the preferential nucleation and growth of SiGe NWs on the catalysts. The selective synthesis process is based on a simple, room-temperature reduction of gold salts (Au³âºCl4⁻) in aqueous solution, which provides well-organized Au catalysts. By optimizing the reduction process, we are able to generate a bidimensional regular array of Au catalysts with self-limited sizes positioned in SiO2-free windows opened in a SiO2/Si(111) substrate by FIB patterning. Such Au catalysts subsequently serve as preferential nucleation and growth sites of well-organized NWs. Furthermore, these NWs with tunable position and size exhibit the relevant features and bright luminescence that would find several applications in optoelectronic nanodevices.

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We report on the optical properties of SiGe nanowires (NWs) grown by molecular beam epitaxy (MBE) in ordered arrays on SiO2/Si(111) substrates. The production method employs Au catalysts with self-limited sizes deposited in SiO2-free sites opened-up in the substrate by focused ion beam patterning for the preferential nucleation and growth of these well-organized NWs. The NWs thus produced have a diameter of 200 nm, a length of 200 nm, and a Ge concentration x = 0.15. Their photoluminescence (PL) spectra were measured at low temperatures (from 6 to 25 K) with excitation at 405 and 458 nm. There are four major features in the energy range of interest (980-1120 meV) at energies of 1040.7, 1082.8, 1092.5, and 1098.5 meV, which are assigned to the NW-transverse optic (TO) Si-Si mode, NW-transverse acoustic (TA), Si-substrate-TO and NW-no-phonon (NP) lines, respectively. From these results the NW TA and TO phonon energies are found to be 15.7 and 57.8 meV, respectively, which agree very well with the values expected for bulk Si1- x Ge x with x = 0.15, while the measured NW NP energy of 1099 meV would indicate a bulk-like Ge concentration of x = 0.14. Both of these concentrations values, as determined from PL, are in agreement with the target value. The NWs are too large in diameter for a quantum confinement induced energy shift in the band gap. Nevertheless, NW PL is readily observed, indicating that efficient carrier recombination is occurring within the NWs.

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BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

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BACKGROUND AND PURPOSE: Deriving accurate language lateralization from fMRI studies in the clinical context can be difficult, with 10%-20% incorrect conclusions. Most interpretations are qualitative, performed by neuroimaging experts. Quantitative lateralization has been widely described but with little implementation in the clinical setting and is disadvantaged by the use of arbitrary threshold techniques. We investigated the application and utility of a nonthreshold CLI, in a clinical setting, as applied by a group of practicing neuroradiologists. MATERIALS AND METHODS: Twenty-two patients with known language lateralization (11 left and 11 nonleft dominant) had their images reviewed by 8 neuroradiologists in 2 settings, all randomized, once by using a CLI and once without using a CLI. For each review, neuroradiologists recorded their impressions of lateralization for each language sequence, the overall lateralization conclusion, their impression of scan quality and noise, and the subjective confidence in their conclusion. RESULTS: The inter-rater κ for lateralization was 0.64, which increased to 0.70 with the use of CLI. The group accuracy of overall lateralization was 78%, which increased to 81% with the use of a CLI. Using a CLI removed 2 instances of significant errors, with a neuroradiologist's impression of left lateralization in a patient with known right lateralization. Using a CLI had no effect on examinations with conclusions formed with either high confidence or no confidence. CONCLUSIONS: Although the overall clinical benefit of a CLI is modest, the most significant impact is to reduce the most harmful misclassification errors, particularly in fMRI examinations that are suboptimal.

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BACKGROUND: Both leprosy and human immunodeficiency virus (HIV) are infectious diseases, and are an important global health problem. Patients with leprosy who are co-infected with HIV seem to be at higher risk of developing leprosy reactions. AIM: To examine the histological features of leprosy in patients with HIV and leprosy co-infection, particularly to determine whether the typical leprosy histopathology is present in skin biopsies, and to assess the histological features of leprosy reactions in co-infected patients. METHODS: This was a matched cohort study with 11 co-infected patients and 31 HIV-negative patients with leprosy. A structured protocol for skin-biopsy evaluation was followed, focusing on inflammation of the skin and dermal nerves. RESULTS: Of the 11 HIV-positive patients, 7 (63%) had borderline tuberculoid (BT) leprosy and 5 (70%) of these 7 patients had developed a type 1 reaction. The lesions in these patients were immunologically active, with 100% of biopsies having evidence of compact granulomas, 90% evidence of oedema and 30% evidence of necrosis. CONCLUSIONS: In this study, patients co-infected with HIV and M. leprae had the typical histological lesions of leprosy. There was evidence of immune activation in patients who received combination antiretroviral therapy, and these patients had BT leprosy and leprosy-upgrading reactions.

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BACKGROUND: Leprosy is complicated by immunological reactions which can occur before, during and after successful completion of multidrug therapy. Genetic studies have suggested that polymorphisms in toll-like receptors (TLRs) may affect the susceptibility of an individual with leprosy to developing Type 1 reactions. OBJECTIVES: To examine the gene and protein expression of TLRs in the cutaneous lesions of leprosy Type 1 reactions at the onset of reaction and during systemic corticosteroid therapy. METHODS: Patients who were being treated for leprosy type 1 reactions with corticosteroids as part of a randomized controlled trial of corticosteroid treatment had skin biopsies performed before, during and at the end of treatment. The gene and protein expression of TLR2 and TLR4 were measured. RESULTS: We have demonstrated that the gene hARP-P0 is a suitable control gene for TLR gene expression studies in this population. The gene and protein expression of TLR2 and TLR4 were both reduced significantly during corticosteroid treatment. CONCLUSIONS: This is the first study to examine the expression of TLR2 and TLR4 in vivo in individuals experiencing leprosy Type 1 reactions. The data support the possibility of an important role for TLR2 and TLR4 in the pathogenesis of this important complication of leprosy.

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WHAT IS KNOWN AND OBJECTIVE: Intravenous sodium stibogluconate (SbV) is the mainstay of treatment for mucocutaneous leishmaniasis. Incidence of this disease is increasing in the UK, partly because of returning military personnel. SbV has a side effect profile that requires treatment interruption in up to 28% of patients. Side effects can be unpleasant and - in the case of QTc prolongation - dangerous. CASE SUMMARY: A volunteer medical worker returning from Guatemala was diagnosed with mucocutaneous leishmaniasis. Because of previous renal problems, NSAIDs were contraindicated. Severe side effects of myalgia and arthralgia would have necessitated a treatment interruption, but a trial of prednisolone gave excellent symptomatic relief. The patient's QTc, amylase and C-reactive protein also fell following initiation of steroid treatment. The SbV treatment course was completed successfully. WHAT IS NEW AND CONCLUSION: This is the first reported case of the dangerous and disabling side effects of SbV being treated very effectively with glucocorticoids. Of note is the normalization of the apparently sodium stibogluconate-induced prolongation of the QTc interval. Further investigation into this potential beneficial effect is warranted.

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The available treatment options for visceral leishmaniasis (VL) have problems relating to efficacy, adverse effects and cost, making treatment a complex issue. We review the evidence relating to the different methods of treatment in relation to - efficacy and toxicity of the drugs in different areas of the world; ability to monitor side effects, length of treatment; ability of patients to pay for and stay safe during treatment, ability of the healthcare services to give intramuscular, intravenous or oral therapy; the sex and child-bearing potential of the patient and the immune status of the patient. The high mortality of untreated/ poorly treated VL infection makes the decisions paramount, but a unified and coordinated response by each area is likely to be more effective and informative to future policies than an ad hoc response. For patients in resource-rich countries, liposomal amphotericin B appears to be the optimal treatment. In South Asia, miltefosine is being used; the combination of single dose liposomal amphotericin B and short course miltefosine looks encouraging but has the problem of potential reproductive toxicities in females. In Africa, the evidence to switch from SSG is not yet compelling. The need to monitor and plan for evolving drug failure, secondary to leishmania parasite resistance, is paramount. With a few drugs the options may be limited; however, we await key ongoing trials in both Africa and India to explore the effects of combination treatment. If safe and reliable combinations are revealed by the ongoing studies, it is far from clear as to whether this will avoid leishmania parasite resistance. The development of new drugs to add to the armamentarium is paramount. Lessons can be learnt from the management of diseases such as tuberculosis and malaria in terms of planning the switch to combination treatment. As important as establishing the best choice for specific antileishmanial agent is ensuring treatment centers, which can best manage the problems encountered during treatment, specifically malnutrition, bleeding, intercurrent infections, drug side effects and detecting and treating underlying immunosuppression.

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We report a retrospective and descriptive study of four immunocompromised patients (three with HIV-1 and one with idiopathic CD4+-lymphopenia) with relapsing visceral leishmaniasis seen at the Hospital for Tropical Diseases, London, in whom pentamidine was used as secondary prophylaxis to prevent relapse. Patients experienced between one and four relapses before commencing prophylaxis with subsequent relapse-free periods ranging from 5 to 98 months. Based on these observational data, we recommend large trials to investigate the efficacy of pentamidine over other agents in preventing relapse of VL in the immunocompromised patient.

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The general problem of the pairing of strongly interacting elementary excitations producing new quasiparticles such as polarons arises in many areas of solid state physics. Recent interest in polaron formation in semiconductor quantum dots has been motivated by the need to understand the physical nature of the carrier relaxation processes and their role in quantum-dot based devices. We report on the direct observation of polarons in InAs/GaAs self-assembled quantum dots populated by few electrons where the polarons are strongly coupled modes of quantum dot phonons and electron intersublevel transitions. The degree of coupling is varied in a systematic way in a set of samples having electron intersublevel spacing changing from larger to smaller than the longitudinal optical phonon energy. The signature of polarons is evidenced clearly by the observation of a large (12-20 meV) anticrossing for both InAs and GaAs-like quantum dot phonons using resonant Raman spectroscopy.

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Erythema nodosum leprosum (ENL) is an immune-mediated complication of leprosy presenting with inflammatory skin nodules and involvement of multiple organ systems, often running a protracted course. Immune complex production and deposition as well as complement activation have long been regarded as the principal aetiology of ENL. However, new data show that cell-mediated immunity is also important. We have performed a critical analysis of studies on the pathology of ENL. Our main findings are as follows. ENL is characterised by an inflammatory infiltrate of neutrophils with vasculitis and/or panniculitis. There is deposition of immune complexes and complement together with Mycobacterium leprae antigens in the skin. Changes in serum levels of Igs indicate a transient, localised immune response. The major T-cell subtype in ENL is the CD4 cell, in contrast to lepromatous leprosy where CD8 cells predominate. The cytokines TNFalpha and IL-6 are consistently found whilst IL-4 is low or absent in ENL lesions, indicating a T(H)1 type response. Keratinocyte 1a and intercellular adhesion molecule-1 (ICAM-1) have been shown to be present in the epidermis in ENL, which is evidence of a cell-mediated immune response. Co-stimulatory molecules such as B7-1 have also been studied but further work is needed to draw strong conclusions. We also highlight potential areas for future research.

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BACKGROUND: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. METHODS: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. RESULTS: Reactions were under-diagnosed, with 32-62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34-53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. CONCLUSIONS: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.

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Leprosy type 1 reactions (T1R) are immune-mediated events with inflammation of peripheral nerves and skin. We report the clinical outcomes of a closely monitored open prospective trial in which eight Nepali and 33 Ethiopian patients with T1Rs were treated with an Indian generic formulation of ciclosporin (Cn; 5-7.5 mg/kg/day) for 12 weeks and followed up for 24 weeks after starting treatment. Outcomes were measured using a clinical severity score. Among the Nepalis, 75-100% improved in all acute clinical parameters; 67-100% patients maintained improvement, except for those with acute sensory nerve impairment among whom 67% relapsed after stopping treatment. The skin lesions of all Ethiopians on 5 mg/kg/day of Cn improved and 50-60% had peripheral nerve function improvement. Most Ethiopians needed a higher dose of Cn to improve nerve impairment and neuritis, and 50-78% of them developed worse clinical severity scores when Cn was stopped. Four Ethiopians and two Nepalis developed elevated serum creatinine levels on 7.5 mg/kg/day Cn, and three (9%) Ethiopians developed treatable hypertension. This suggests that Cn monotherapy is an effective treatment for severe T1R with few adverse effects. A dose of 5 mg/kg/day seems efficacious in Nepalis, but a higher dose may be required in Ethiopian patients.

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