Normal, dust-obscured galaxies in the epoch of reionization.

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1-3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4-7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare population of extreme starburst galaxies8-12 and companions of rare quasars13,14. These studies conclude that the contribution of dust-obscured galaxies to the cosmic star formation rate density at z > 6 is sub-dominant. Recent ALMA and Spitzer observations have identified a more abundant, less extreme population of obscured galaxies at z = 3-6 (refs. 15,16). However, this population has not been confirmed in the reionization epoch so far. Here, we report the discovery of two dust-obscured star-forming galaxies at z = 6.6813 ± 0.0005 and z = 7.3521 ± 0.0005. These objects are not detected in existing rest-frame UV data and were discovered only through their far-infrared [C II] lines and dust continuum emission as companions to typical UV-luminous galaxies at the same redshift. The two galaxies exhibit lower infrared luminosities and star-formation rates than extreme starbursts, in line with typical star-forming galaxies at z ≈ 7. This population of heavily dust-obscured galaxies appears to contribute 10-25% to the z > 6 cosmic star formation rate density.

Therapeutic approaches of diametaphyseal radius fractures in children.

BACKGROUND: There are clear standards for when to operate on both distal epiphyseal and diaphyseal forearm fractures in children. However, paediatric surgeons are often faced with fractures in the transition zone between metaphysis and diaphysis. This aim of the study is to compare different treatment approaches for diametaphyseal forearm fractures, to classify different types of these fractures, and to define further assessment parameters and treatment recommendations. METHODS: This retrospective study included all patients with diametaphyseal radial fractures who were seen at a paediatric surgery clinic between 01.01.2010 and 31.12.2013. Patients were treated either non-surgically (C) or surgically using bicortical Kirschner wire (BC-KW), intramedullary K-wire (IM-KW), elastic stable intramedullary nailing (ESIN), or combined bicortical and intramedullary K-wire (BCIM-KW). RESULTS: During the study period, 547 patients presented with forearm fractures of which 88 patients (16%) had a fracture in the diametaphyseal region. The majority of diametaphyseal fractures were greenstick fractures (54.4%) followed by transverse fractures (44.3%). Distal fractures were predominantly treated with bicortical K-wiring (BC-KW, 40.5%) or non-surgically (C, 26.2%). Proximal fractures were treated by ESIN osteosynthesis (50%), followed by IM-KW (30%). Intermediate fractures were just as likely to be treated with one out of the 5 above-mentioned techniques. The ulna was involved in 64 of 88 cases. Depending on the type of fracture, it was treated either by ESIN osteosynthesis or non-surgically. No superior operative technique was identified. CONCLUSIONS: The description of diametaphyseal fractures as a separate entity is important, because the therapy of these fractures is heterogeneous and challenging. A classification into proximal, intermediate, and distal may be useful in clinical decision-making. Despite the retrospective nature of this study, our data suggest that the use of a K-wire or combined technique BCIM-KW-technique, whenever technically feasible, achieves better radiological results without secondary dislocation. Further prospective studies are needed to provide better guidance to trauma surgeons.

Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer's disease.

Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. In this review, we discuss how neurologists manipulate brain oscillations with neuromodulation to treat diseases and how this can be leveraged to improve cognition and pathology underlying AD. While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.

Experimental manipulation of population-level MHC diversity controls pathogen virulence evolution in Mus musculus.

The virulence levels attained by serial passage of pathogens through similar host genotypes are much higher than observed in natural systems; however, it is unknown what keeps natural virulence levels below these empirically demonstrated maximum levels. One hypothesis suggests that host diversity impedes pathogen virulence, because adaptation to one host genotype carries trade-offs in the ability to replicate and cause disease in other host genotypes. To test this hypothesis, with the simplest level of population diversity within the loci of the major histocompatibility complex (MHC), we serially passaged Friend virus complex (FVC) through two rounds, in hosts with either the same MHC genotypes (pure passage) or hosts with different MHC genotypes (alternated passage). Alternated passages showed a significant overall reduction in viral titre (31%) and virulence (54%) when compared to pure passages. Furthermore, a resistant host genotype initially dominated any effects due to MHC diversity; however, when FVC was allowed to adapt to the resistant host genotype, predicted MHC effects emerged; that is, alternated lines show reduced virulence. These data indicate serial exposure to diverse MHC genotypes is an impediment to pathogen adaptation, suggesting genetic variation at MHC loci is important for limiting virulence in a rapidly evolving pathogen and supports negative frequency-dependent selection as a force maintaining MHC diversity in host populations.

Enhanced Multi-MeV Photon Emission by a Laser-Driven Electron Beam in a Self-Generated Magnetic Field.

We use numerical simulations to demonstrate that a source of collimated multi-MeV photons with high conversion efficiency can be achieved using an all-optical single beam setup at an intensity of 5×10^{22} W/cm^{2} that is already within reach of existing laser facilities. In the studied setup, an unprecedented quasistatic magnetic field (0.4 MT) is driven in a significantly overdense plasma, coupling three key aspects of laser-plasma interactions at high intensities: relativistic transparency, direct laser acceleration, and synchrotron photon emission. The quasistatic magnetic field enhances the photon emission process, which has a profound impact on electron dynamics via radiation reaction and yields tens of TW of directed MeV photons for a PW-class laser.

How young people describe the impact of living with and beyond a cancer diagnosis: feasibility of using social media as a research method.

OBJECTIVE: Young people with cancer exhibit unique needs. During a time of normal physical and psychological change, multiple disease and treatment-related symptoms cause short and long-term physical and psychosocial effects. Little is known about how young people cope with the impact of cancer and its treatment on daily routines and their strategies to manage the challenges of cancer and treatments. We aimed to determine how young people describe these challenges through a social media site. METHODS: Using the principles of virtual ethnography and watching videos on a social media site we gathered data from young people describing their cancer experience. Qualitative content analysis was employed to analyse and interpret the narrative from longitudinal 'video diaries' by 18 young people equating to 156 films and 27 h and 49 min of recording. Themes were described then organized and clustered into typologies grouping commonalities across themes. RESULTS: Four typologies emerged reflective of the cancer trajectory: treatment and relenting side effects, rehabilitation and getting on with life, relapse, facing more treatment and coming to terms with dying. CONCLUSIONS: This study confirms the need for young people to strive towards normality and creating a new normal, even where uncertainty prevailed. Strategies young people used to gain mastery over their illness and the types of stories they choose to tell provide the focus of the main narrative. Social Media sites can be examined as a source of data, to supplement or instead of more traditional routes of data collection known to be practically challenging with this population. Copyright © 2016 John Wiley & Sons, Ltd.

Intense star formation within resolved compact regions in a galaxy at z = 2.3.

Massive galaxies in the early Universe have been shown to be forming stars at surprisingly high rates. Prominent examples are dust-obscured galaxies which are luminous when observed at sub-millimetre wavelengths and which may be forming stars at a rate of 1,000 solar masses (M(middle dot in circle)) per year. These intense bursts of star formation are believed to be driven by mergers between gas-rich galaxies. Probing the properties of individual star-forming regions within these galaxies, however, is beyond the spatial resolution and sensitivity of even the largest telescopes at present. Here we report observations of the sub-millimetre galaxy SMMJ2135-0102 at redshift z = 2.3259, which has been gravitationally magnified by a factor of 32 by a massive foreground galaxy cluster lens. This magnification, when combined with high-resolution sub-millimetre imaging, resolves the star-forming regions at a linear scale of only 100 parsecs. We find that the luminosity densities of these star-forming regions are comparable to the dense cores of giant molecular clouds in the local Universe, but they are about a hundred times larger and 10(7) times more luminous. Although vigorously star-forming, the underlying physics of the star-formation processes at z approximately 2 appears to be similar to that seen in local galaxies, although the energetics are unlike anything found in the present-day Universe.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

ENCCA WP17-WP7 consensus paper on teenagers and young adults (TYA) with bone sarcomas.

Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.

Description of Dientamoeba fragilis cyst and precystic forms from human samples.

Dientamoeba fragilis is a common enteropathogen of humans. Recently a cyst stage of the parasite was described in an animal model; however, no cyst stage has been described in detail from clinical samples. We describe both cyst and precystic forms from human clinical samples.

'Just in case': the fertility information needs of teenagers and young adults with cancer.

Understanding the reproductive and fertility concerns of teenagers and young adults with cancer (TYA) is one aspect of comprehensive age appropriate care. However, limited options for fertility preservation, coupled with vague policy recommendations, give rise to variations in information-sharing between health care professionals and TYAs, particularly as it involves sensitive discussions regarding the short- and long-term effects of cancer and treatments on fertility and reproduction. This paper presents findings from a wider evaluation at a specialist unit for TYAs with cancer. Forty people participated in semi-structured interviews, including 20 young people, parents and partners. Young people were between 2 months and 4 years from finishing treatment. Most young people received mixed levels of information on fertility and counselling before treatment. Diagnosis in the early teens meant how, and from whom, young people received information varied. Young women tended to receive incomplete information. The majority of young people were unaware of their fertility status after treatment had finished. Findings point to the inherent challenges that exist in ensuring young people aged between 13 and 25 years receive comprehensive information on their fertility and potential risk, as well as advice on how to determine their fertility status after treatment has finished.

Development of an infection prevention and control pathway to facilitate high-throughput cataract surgery in Scotland.

INTRODUCTION: Cataract surgery offers significant improvement to quality of life for patients with cataracts. However, there are growing waiting lists and challenges in providing this type of surgery in a timely manner. Feedback from stakeholders had previously indicated infection prevention and control (IPC) as a potential barrier to high-throughput surgery. Antimicrobial Resistance and Healthcare Associated Infection Scotland was asked to support the implementation of high-throughput cataract surgery aimed at addressing these challenges. AIM: To develop an IPC pathway to facilitate high-throughput surgery. This would be based on best practice, and would address any barriers identified by stakeholders. METHODS: A short life working group with input from key stakeholders, including clinical teams, was established. A rapid literature review was also undertaken. RESULTS: An agreed patient pathway was developed, with the aim of helping to facilitate high-throughput surgery. Pre-, intra- and postoperative phases were considered. Where literature was unavailable, expert/consensus opinion was utilized. Facilities for high-throughput surgery were also considered, including the Jack and Jill theatre arrangement which lends itself well to this concept. CONCLUSION: Through collaboration with stakeholders, an IPC pathway was developed to facilitate high-throughput cataract surgery and address any potential IPC barriers to implementation. The process and the output described could be utilized to develop similar pathways for other surgeries that lend themselves well to high throughput, improving quality of life for patients and reducing waiting times. This study highlights the importance of establishing surveillance for postoperative endophthalmitis following implementation.

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis.

BACKGROUND: Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2)). METHODS: Questionnaires were completed by 91 men (response rate=86.67%) at T1 and 78 (85.71% response rate) at T2. RESULTS: In all, 44 (56.41%) banked sperm. They were younger and less likely to have children than non-bankers. In a subset of men who were not sure if they wanted children in the future (n=36), 24 banked sperm. Among this group, those who banked were younger, more satisfied with clinic appointments and less worried about the health of future children. At T2, there were no differences in quality of life between bankers and non-bankers. CONCLUSION: For those who are uncertain about future reproductive plans, decisions depend on their health on diagnosis and satisfaction with clinic care. We conclude that extra care should be taken in counselling younger men who may have given little consideration to future parenting. Results support previous findings that the role of the doctor is vital in facilitating decisions, especially for those who are undecided about whether they wanted children in the future or not.

The impact of a managed transition of care upon psychosocial characteristics and patient satisfaction in a cohort of adult survivors of childhood cancer.

OBJECTIVE: Many adult survivors of childhood cancer receive care in paediatric departments, despite national policy to transition their care to adult services. When long-term follow-up care for survivors of childhood cancer in our region moved from a paediatric to an adult environment in 2009, we prospectively assessed the impact of this change on patient satisfaction. METHODS: Questionnaire data were collected in paediatric and adult clinical environments regarding the level of satisfaction with care and potential mediators: quality of life, psychological health and social difficulties. Predictors of satisfaction and optimum longitudinal risk-based care were described using path analysis and compared with previously described models. RESULTS: There was no significant difference in satisfaction between the paediatric and adult settings. Short waiting times and increased understanding of the purpose of follow-up were significantly associated with increased satisfaction. Those with a higher perception of health problems and those that were older were more likely to not attend all of their clinic appointments. CONCLUSIONS: Within our service, transition to adult care did not impact significantly upon patient satisfaction. Shorter waits and knowing why participants were attending the clinic increased satisfaction. Joint working between adult and paediatric cancer professionals enabled adult survivors of childhood cancer to receive highly satisfactory care in adult services.

Subtype distribution of Blastocystis isolates identified in a Sydney population and pathogenic potential of Blastocystis.

Blastocystis is one of the most common enteric parasites present in humans. There is still much uncertainty about the pathogenic potential of this parasite, and it was suggested that its pathogenicity could be subtype-related. This report aimed to study 98 Blastocystis isolates found in human stool specimens to identify the subtypes present and carry out phylogenetic analysis on these isolates. This study also aimed to show the relationship between subtype and symptoms. Five-hundred and thirteen stool samples were submitted to five different diagnostic techniques for the detection of Blastocystis. Polymerase chain reaction (PCR)-positive samples were then sequenced and the small subunit (SSU) rDNA sequences were aligned and submitted to phylogenetic analysis. Ninety-eight samples were positive by any of the diagnostic methods for Blastocystis and 96 were positive by PCR. There were seven different subtypes (1, 2, 3, 4, 6, 7 and 8) identified by PCR and sequencing. This is the first large-scale study to examine the occurrence of Blastocystis in Australia. This study reports the high incidence of subtype 3 (44 %) in this population and discusses the emerging idea of subtype-dependent pathogenicity.

Improving outcomes for teenagers and young adults (TYA) with cancer.

The management of TYA with cancer is characterized by biological features in comparison to children. Therefore specialized treatment units have been established within professional structures of care for this group, and a European multidisciplinary framework for the treatment of TYA with cancer was founded.Objectives are to promote interdisciplinary collaboration and provide strategic concepts to improve patient care centered to the special needs of this age group. Access to clinical trials for all TYA in the EU will be improved and research initiated, examining biology, epidemiology and health services.Special goals of the interprofessional cooperation are:Different measurements are discussed improving outcomes for TYA is proceeding at different speeds in different parts of the world. In some there are established teams, bringing together paediatric and adult specialists from many healthcare professions, reviewing and contributing to the optimal care of all TYA with cancer as part of national health policy.

Cancer burden in adolescents and young adults in Europe.

BACKGROUND: Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries. PATIENTS AND METHODS: We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population. RESULTS: Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment. CONCLUSIONS: Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden.

In vitro susceptibility testing of Dientamoeba fragilis.

Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to evaluate the susceptibility of D. fragilis to several commonly used antiparasitic agents: diloxanide furoate, furazolidone, iodoquinol, metronidazole, nitazoxanide, ornidazole, paromomycin, secnidazole, ronidazole, tetracycline, and tinidazole. Antibiotic susceptibility testing was performed on four clinical strains of D. fragilis, designated A, E, M, and V, respectively. Molecular testing followed, and all strains were determined to be genotype 1. The activities of antiprotozoal compounds at concentrations ranging from 2 µg/ml to 500 µg/ml were determined via cell counts of D. fragilis trophozoites grown in dixenic culture. Minimum lethal concentrations (MLCs) were as follows: ornidazole, 8 to 16 µg/ml; ronidazole, 8 to 16 µg/ml; tinidazole, 31 µg/ml; metronidazole, 31 µg/ml; secnidazole, 31 to 63 µg/ml; nitazoxanide, 63 µg/ml; tetracycline, 250 µg/ml; furazolidone, 250 to 500 µg/ml; iodoquinol, 500 µg/ml; paromomycin, 500 µg/ml; and diloxanide furoate, >500 µg/ml. This is the first study to report the profiles of susceptibility to a wide range of commonly used treatments for clinical isolates of D. fragilis. Our study indicated 5-nitroimidazole derivatives to be the most active compounds in vitro against D. fragilis.

Comparing school environments with and without legislation for the prevention and management of anaphylaxis.

BACKGROUND: School personnel in contact with students with life-threatening allergies often lack necessary supports, creating a potentially dangerous situation. Sabrina's Law, the first legislation in the world designed to protect such children, requires all Ontario public schools to have a plan to protect children at risk. Although it has captured international attention, the differences a legislative approach makes have not been identified. Our study compared the approaches to anaphylaxis prevention and management in schools with and without legislation. METHODS: Legislated (Ontario) and nonlegislated (Alberta, British Columbia, Newfoundland and Labrador, and Quebec) environments were compared. School board anaphylaxis policies were assessed for consistency with Canadian anaphylaxis guidelines. Parents of at-risk children and school personnel were surveyed to determine their perspectives on school practices. School personnel's EpiPen5 technique was assessed. RESULTS: Consistency of school board policies with anaphylaxis guidelines was significantly better in a legislated environment (P=0.009). Parents in a legislated environment reported more comprehensive anaphylaxis emergency forms (P<0.001), while school personnel in nonlegislated environments reported more comprehensive forms (P=0.004). Despite school personnel in both environments receiving EpiPen5 training (>80%), suboptimal technique was commonly observed. However, school personnel in the legislated environment had better technique (P<0.001). CONCLUSION: Our results suggest that school boards in legislated environments have made greater efforts to support students at risk for anaphylaxis compared to nonlegislated environments. However, significant gaps exist in both environments, especially with respect to EpiPen5 administration, content, and distribution of anaphylaxis emergency forms, and awareness of school procedures by school personnel and parents.

Myositis due to the microsporidian Anncaliia (Brachiola) algerae in a lung transplant recipient.

Microsporidia are obligate intracellular parasites, more closely related to fungi than protozoa on molecular phylogenetic analysis, and are known to be a rare cause of opportunistic infection in immune compromised patients including human immunodeficiency virus-positive patients and solid organ transplant recipients. We report the first case to our knowledge of microsporidial myositis in a lung transplant recipient. He was 49 years old and had received a lung transplant in 2000 for cystic fibrosis. He presented in 2009 with fevers, chronic diarrhea, myalgia, and pancytopenia, and developed progressive weakness and neurological symptoms before his death 35 days after hospital admission. Multiple investigations, including stool culture, rectal biopsy, colonoscopy, cerebrospinal fluid examination, bone marrow biopsy, lung biopsy, and bronchoalveolar lavage, failed to reveal a definite cause for the patient's deterioration. The diagnosis of microsporidial infection was made on post-mortem light microscopic examination of tissue sections of the tongue and deltoid muscle. Light microscopy diagnosed a microsporidial myositis, confirmed by transmission electron microscopy, which suggested that the organism was Brachiola species. The identity of the organism was confirmed by polymerase chain reaction as Brachiola algerae (recently renamed Anncaliia algerae). The case highlights the need to consider protozoal organisms in the differential diagnosis of myalgia and multisystemic infections in immune compromised patients.