Palliative Care in Adolescents and Young Adults With Cancer-Why Do Adolescents Need Special Attention?

Meeting shortfalls in the provision of care to adolescents and young adults with cancer has focused largely on improving outcomes and psychosocial support. A significant percentage of adolescents and young adults with cancer will die of disease because of initial poor prognosis conditions or disease relapse. In adults, progress has been made in the concept of an integrated cancer/palliative care service.

Protocadherin-1 is essential for cell entry by New World hantaviruses.

The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS). No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1) as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV).

Are inequalities in cancer diagnosis through emergency presentation narrowing, widening or remaining unchanged? Longitudinal analysis of English population-based data 2006-2013.

Background: Diagnosis of cancer through emergency presentation is associated with poorer prognosis. While reductions in emergency presentations have been described, whether known sociodemographic inequalities are changing is uncertain.

Methods: We analysed 'Routes to Diagnosis' data on patients aged ≥25 years diagnosed in England during 2006-2013 with any of 33 common or rarer cancers.

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes.

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50-85% at various anatomical sites, determine skeletal health throughout life.

Trends in Hospital Admissions for Nonfatal Adversity-Related Injury Among Youths in England, 2002-2016.

This study examines temporal trends in nonfatal adversity-related injury admissions overall and for self-inflicted injury among young people in England.

Discussing death: Making end of life implicit or explicit in paediatric palliative care consultations.

Objective: To consider whether and how family members and clinicians discuss end of life during paediatric palliative care consultations.

Methods: Nine naturally occurring paediatric palliative care consultations were video recorded and analysed using conversation analytic methods.

Analysis: Focusing on three consultations in which end of life was treated as a certain outcome, analysis explored ways in which end of life was made either implicit or explicit within these consultations.

Biomechanics of the jaw of the durophagous bonnethead shark.

Durophagy in chondrichthyan fishes is thought to entail a set of morphological characteristics, such as hypertrophied adductor muscles, molariform teeth, and high bite forces. However, these characteristics are not common to all durophagous chondrichthyans. In some durophagous chondrichthyans, the jaws are better suited biomechanically to resist bending in the area where prey is processed.

Stage-specific incidence trends of melanoma in an English region, 1996-2015: longitudinal analyses of population-based data.

The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group.

Vision Impairment and Risk of Dementia: Findings from the English Longitudinal Study of Ageing.

Objectives: To determine whether vision impairment is independently associated cross-sectionally and longitudinally with dementia.

Design: Retrospective cohort study.

Setting: English Longitudinal Study of Ageing.

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.

Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model.

A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.

The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells.

Associations between diagnostic pathways and care experience in colorectal cancer: evidence from patient-reported data.

Objective: To examine how different pathways to diagnosis of colorectal cancer may be associated with the experience of subsequent care.

Design: Patient survey linked to information on diagnostic route.English patients with colorectal cancer (analysis sample n=6837) who responded to a patient survey soon after their hospital treatment.

Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children's Health Service.

Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed.

Pediatric Headache Clinic Model: Implementation of Integrative Therapies in Practice.

The demand for integrative medicine has risen in recent years as research has demonstrated the efficacy of such treatments. The public has also become more conscientious of the potential limitations of conventional treatment alone. Because primary headache syndromes are often the culmination of genetics, lifestyle, stress, trauma, and environmental factors, they are best treated with therapies that are equally multifaceted.

Post-Exposure Protection in Mice against Sudan Virus by a Two Antibody Cocktail.

Sudan virus (SUDV) and Ebola viruses (EBOV) are both members of the genus and have been sources of epidemics and outbreaks for several decades. We present here the generation and characterization of cross-reactive antibodies to both SUDV and EBOV, which were produced in a cell-free system and protective against SUDV in mice. A non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of SUDV-Boniface (8A).

Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs.

Healthcare Users' Experiences of Communicating with Healthcare Professionals About Children Who Have Life-Limiting Conditions: A Qualitative Systematic Review.

Background: Globally, an estimated eight million children could benefit from palliative care each year. Effective communication about children with life-limiting conditions is well recognized as a critical component of high-quality pediatric palliative care.

Objective: To synthesize existing qualitative research exploring healthcare users' experiences of communicating with healthcare professionals about children with life-limiting conditions.

An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy.

C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1-5 linked to repeats 18-20 (FH), that was effective in experimental C3G.

Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohort.

Background: Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness.

Methods: We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12-24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015.

Evaluation of a countrywide implementation of the world health organisation surgical safety checklist in Madagascar.

Background: The 2009 World Health Organisation (WHO) surgical safety checklist significantly reduces surgical mortality and morbidity (up to 47%). Yet in 2016, only 25% of East African anesthetists regularly use the checklist. Nationwide implementation of the checklist is reported in high-income countries, but in low- and middle-income countries (LMICs) reports of successful implementations are sparse, limited to single institutions and require intensive support.

Visible-Light Photoredox/Nickel Dual Catalysis for the Cross-Coupling of Sulfinic Acid Salts with Aryl Iodides.

An efficient cross-coupling of sodium or lithium sulfinates with aryl iodides, using a combination of nickel and photoredox catalysis, is described. The dual catalyst system enables a versatile synthesis of aryl sulfones at room temperature in good yields and displays a broad functional group compatibility. The potential utility of this method in the late-stage diversification of complex molecules and in the conversion of organolithium reagents and sulfur dioxide into sulfones is demonstrated.

A Retrospective Review of Resuscitation Planning at a Children's Hospital.

Resuscitation plans (RP) are an important clinical indicator relating to care at the end of life in paediatrics. A retrospective review of the medical records of children who had been referred to the Royal Children's Hospital, Brisbane, Australia who died in the calendar year 2011 was performed. Of 62 records available, 40 patients (65%) had a life limiting condition and 43 medical records (69%) contained a documented RP.

No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes.

Background: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance.

Aim: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners.

Methods: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK).