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A novel multicomponent alloy, V2.5Cr1.2WMoCo0.04, produced from elements expected to favour a BCC crystal structure, and to be suitable for high temperature environments, was fabricated by arc melting and found to exhibit a multiphase dendritic microstructure with W-rich dendrites and V–Cr segregated to the inter-dendritic cores. The as-cast alloy displayed an apparent single-phase XRD pattern. Following heat treatment at 1187 °C for 500 h the alloy transformed into three different distinct phases - BCC, orthorhombic, and tetragonal in crystal structure. This attests to the BCC crystal structure observed in the as-cast state being metastable. The radiation damage response was investigated through room temperature 5 MeV Au+ ion irradiation studies. Metastable as-cast V2.5Cr1.2WMoCo0.04 shows good resistance to radiation induced damage up to 40 displacements per atom (dpa). 96 wt% of the as-cast single-phase BCC crystal structure remained intact, as exhibited by grazing incidence X-ray diffraction (GI-XRD) patterns, whilst the remainder of the alloy transformed into an additional BCC crystal structure with a similar lattice parameter. The exceptional phase stability seen here is attributed to a combination of self-healing processes and the BCC structure, rather than a high configurational entropy, as has been suggested for some of these multicomponent “High Entropy Alloy” types. The importance of the stability of metastable high entropy alloy phases for behaviour under irradiation is for the first time highlighted and the findings thus challenge the current understanding of phase stability after irradiation of systems like the HEAs.

Purpose: To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. Methods: A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Results: Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3–19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Conclusions: Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed. © 2017, Springer-Verlag Berlin Heidelberg and ESICM.

Adjuvant therapy is an important component in the management of breast cancer. Receipt of indicated adjuvant chemotherapy, radiation, and hormonal therapy significantly reduces disease recurrence and improves survival among women with early-stage breast cancer (Clarke et al. 2005; Early Breast Cancer Trialists’ Collaborative Group 2005). The National Institutes of Health (NIH) and a number of other leading medical organizations have developed evidence-based guidelines and recommendations regarding the use of adjuvant therapy for breast cancer (Eifel et al. 2001; National Comprehensive Cancer Network 2014). Despite the documented health benefits and recommendations, receipt of adjuvant therapy varies by several nonclinical factors such as race, health insurance, socioeconomic status (SES), and treatment facility characteristics (Griggs et al. 2007; Byers et al. 2008; Wu et al. 2008, 2012; Bhargava and Du 2009; Buist et al. 2009; Yen et al. 2010; Freedman et al. 2011). For example, black women have been shown to be less likely to receive adjuvant chemotherapy (Bhargava and Du 2009; Freedman et al. 2011) and hormonal therapy (Freedman et al. 2011). Compared with private insurance, having Medicaid insurance has been shown to be associated with lower rates of guideline-concordant chemotherapy (Wu et al. 2012). SES has been shown to be associated with breast cancer treatment patterns (Griggs et al. 2007; Byers et al. 2008; Wu et al. 2012), with patients of lower SES experiencing reduced rates of guideline-concordant chemo- and hormonal therapy (Wu et al. 2012). Receipt of adjuvant therapy may depend on treatment facility characteristics, with higher rates of guideline-concordance reported at American College of Surgeons’ Commission on Cancer (CoC)-approved cancer centers (Wu et al. 2012). Increasing age is inversely associated with adjuvant therapy use (Buist et al. 2009; Yen et al. 2010). Although previous studies have provided insight into the factors potentially influencing receipt of adjuvant therapy, little is known about the delivery of adjuvant therapy in nonmetropolitan settings. Rural breast cancer patients may be less likely to receive new treatments due to slower adoption of new technologies in rural locations. Rural patients may also face additional barriers to treatment, such as a lack of experienced providers, lack of technological support, and longer travel distances (Arrington et al. 2013). The present study examines the delivery of adjuvant therapy for breast cancer in the largely rural region of southwest Georgia (SWGA). Specifically, we examine the factors associated with receiving guideline-concordant (1) adjuvant chemotherapy, (2) adjuvant radiation therapy, and (3) adjuvant hormonal therapy, considered both individually and for all adjuvant therapies jointly, among SWGA breast cancer patients. This study presents an innovative approach to constructing a summary measure of “guideline-concordance” when there are multiple possible treatment components (here, different types of adjuvant therapy following breast cancer surgery) and the recommended treatment package for a patient is conditional on her particular clinical circumstances. Whether a patient is guideline-concordant, so defined, becomes an important indicator of the quality of cancer care. Because the summary measure is a two-level (Yes/No) variable, the patient- and provider-level determinants of variations in guideline-concordance can thus be investigated directly through binary logistic regression. In addition, this study examines guideline-concordance in breast cancer treatment within an important and relatively understudied segment of the U.S. population.

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The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been named 'dematiaceous'. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana-Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients. © 2014 European Society of Clinical Microbiology and Infectious Diseases.

The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive treatment was reviewed. In addition, remarks about antifungal susceptibility testing were made. © 2013 European Society of Clinical Microbiology and Infectious Diseases.

This concise text delivers a basic introduction to neurology and is designed for use by medical students during their rotation in neurology and related disciplines. Updated and expanded, this second edition follows the same order as the first, starting with how to approach a patient with a neurologic problem followed by the latest information on the phenomenology, pathophysiology and symptoms of common adult and pediatric neurologic diseases. Supplementing the learning experience are clinical cases that begin each chapter and videos of examples ranging from how to perform the normal neurologic exam to abnormal exam findings. Easy-to-read and richly illustrated, Fundamentals of Neurologic Disease, 2nd Edition is an invaluable resource for anyone seeking to learn the fundamentals of neurology.

Mucosal candidiasis is frequent in immunocompromised HIV-infected highly active antiretroviral (HAART) naive patients or those who have failed therapy. Mucosal candidiasis is a marker of progressive immune deficiency. Because of the frequently marked and prompt immune reconstitution induced by HAART, there is no recommendation for primary antifungal prophylaxis of mucosal candidiasis in the HIV setting in Europe, although it has been evidenced as effective in the pre-HAART era. Fluconazole remains the first line of therapy for both oropharyngeal candidiasis and oesophageal candidiasis and should be preferred to itraconazole oral solution (or capsules when not available) due to fewer side effects. For patients who still present with fluconazole-refractory mucosal candidiasis, oral treatment with any other azole should be preferred based on precise Candida species identification and susceptibility testing results in addition to the optimization of HAART when feasible. For vaginal candidiasis, topical therapy is preferred. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

The process to develop a guideline in a European setting remains a challenge. The ESCMID Fungal Infection Study Group (EFISG) successfully achieved this endeavour. After two face-to-face meetings, numerous telephone conferences, and email correspondence, an ESCMID task force (basically composed of members of the Society's Fungal Infection Study Group, EFISG) finalized the ESCMID diagnostic and management/therapeutic guideline for Candida diseases. By appreciating various patient populations at risk for Candida diseases, four subgroups were predefined, mainly ICU patients, paediatric, HIV/AIDS and patients with malignancies including haematopoietic stem cell transplantation. Besides treatment recommendations, the ESCMID guidelines provide guidance for diagnostic procedures. For the guidelines, questions were formulated to phrase the intention of a given recommendation, for example, outcome. The recommendation was the clinical intervention, which was graded by a score of A-D for the 'Strength of a recommendation'. The 'level of evidence' received a score of I-III. The author panel was approved by ESCMID, European Organisation for Research and Treatment of Cancer, European Group for Blood and Marrow Transplantation, European Society of Intensive Care Medicine and the European Confederation of Medical Mycology. The guidelines followed the framework of GRADE and Appraisal of Guidelines, Research, and Evaluation. The drafted guideline was presented at ECCMID 2011 and points of discussion occurring during that meeting were incorporated into the manuscripts. These ESCMID guidelines for the diagnosis and management of Candida diseases provide guidance for clinicians in their daily decision-making process. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

This part of the EFISG guidelines focuses on non-neutropenic adult patients. Only a few of the numerous recommendations can be summarized in the abstract. Prophylactic usage of fluconazole is supported in patients with recent abdominal surgery and recurrent gastrointestinal perforations or anastomotic leakages. Candida isolation from respiratory secretions alone should never prompt treatment. For the targeted initial treatment of candidaemia, echinocandins are strongly recommended while liposomal amphotericin B and voriconazole are supported with moderate, and fluconazole with marginal strength. Treatment duration for candidaemia should be a minimum of 14days after the end of candidaemia, which can be determined by one blood culture per day until negativity. Switching to oral treatment after 10days of intravenous therapy has been safe in stable patients with susceptible Candida species. In candidaemia, removal of indwelling catheters is strongly recommended. If catheters cannot be removed, lipid-based amphotericin B or echinocandins should be preferred over azoles. Transoesophageal echocardiography and fundoscopy should be performed to detect organ involvement. Native valve endocarditis requires surgery within a week, while in prosthetic valve endocarditis, earlier surgery may be beneficial. The antifungal regimen of choice is liposomal amphotericin B+/-flucytosine. In ocular candidiasis, liposomal amphotericin B+/-flucytosine is recommended when the susceptibility of the isolate is unknown, and in susceptible isolates, fluconazole and voriconazole are alternatives. Amphotericin B deoxycholate is not recommended for any indication due to severe side effects. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Invasive candidiasis (IC) is a relatively common syndrome in neonates and children and is associated with significant morbidity and mortality. These guidelines provide recommendations for the prevention and treatment of IC in neonates and children. Appropriate agents for the prevention of IC in neonates at high risk include fluconazole (A-I), nystatin (B-II) or lactoferrin±Lactobacillus (B-II). The treatment of IC in neonates is complicated by the high likelihood of disseminated disease, including the possibility of infection within the central nervous system. Amphotericin B deoxycholate (B-II), liposomal amphotericin B (B-II), amphotericin B lipid complex (ABLC) (C-II), fluconazole (B-II), micafungin (B-II) and caspofungin (C-II) can all be potentially used. Recommendations for the prevention of IC in children are largely extrapolated from studies performed in adults with concomitant pharmacokinetic data and models in children. For allogeneic HSCT recipients, fluconazole (A-I), voriconazole (A-I), micafungin (A-I), itraconazole (B-II) and posaconazole (B-II) can all be used. Similar recommendations are made for the prevention of IC in children in other risk groups. With several exceptions, recommendations for the treatment of IC in children are extrapolated from adult studies, with concomitant pharmacokinetic studies. Amphotericin B deoxycholate (C-I), liposomal amphotericin B (A-I), ABLC (B-II), micafungin (A-I), caspofungin (A-I), anidulafungin (B-II), fluconazole (B-I) and voriconazole (B-I) can all be used. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Fungal diseases still play a major role in morbidity and mortality in patients with haematological malignancies, including those undergoing haematopoietic stem cell transplantation. Although Aspergillus and other filamentous fungal diseases remain a major concern, Candida infections are still a major cause of mortality. This part of the ESCMID guidelines focuses on this patient population and reviews pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida diseases. Anti-Candida prophylaxis is only recommended for patients receiving allogeneic stem cell transplantation. The authors recognize that the recommendations would have most likely been different if the purpose would have been prevention of all fungal infections (e.g. aspergillosis). In targeted treatment of candidaemia, recommendations for treatment are available for all echinocandins, that is anidulafungin (AI), caspofungin (AI) and micafungin (AI), although a warning for resistance is expressed. Liposomal amphotericin B received a BI recommendation due to higher number of reported adverse events in the trials. Amphotericin B deoxycholate should not be used (DII); and fluconazole was rated CI because of a change in epidemiology in some areas in Europe. Removal of central venous catheters is recommended during candidaemia but if catheter retention is a clinical necessity, treatment with an echinocandin is an option (CIIt). In chronic disseminated candidiasis therapy, recommendations are liposomal amphotericin B for 8weeks (AIII), fluconazole for >3months or other azoles (BIII). Granulocyte transfusions are only an option in desperate cases of patients with Candida disease and neutropenia (CIII). © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Growth of moulds in moisture-damaged buildings has various adverse health effects, such as allergic diseases. To protect the inhabitants being harmed by moulds or their toxins, indoor microbiota need to be investigated; therefore an efficient identification method is needed. To assess the diversity of fungi colonizing temporarily damp indoor building materials in northern European countries (Finland, Sweden, Denmark, and U.K.), 62 samples from 22 houses were taken. In total 234 pure cultures were acquired and identified using morphological and molecular techniques (sequence comparison of rDNA internal transcribed spacer and BT2 [partial b-tubulin]). Comparing CBS-database with GenBank by blasting ITS and BT2 sequences we found correct identification down to species level by GenBank in only 12.8 % and 16.0 %, respectively. GenBank is an inadequate tool for reliable identification of less common fungi. Final identification of fungi is based on internal databases at CBS validated by ex-type strains. Within all samples we identified strains affiliated to 43 species belonging to 20 genera. Predominant were oligotrophic fungi such as Penicillium, Aspergillus and Cladosporium; some may serve as indicator organisms for indoor moisture problems. Based on final identifications, species-specific probes were developed for fast identification of moulds in indoor environments.