'It is life threatening but I don't mind'. A qualitative study using photo elicitation interviews to explore adolescents' experiences of renal replacement therapies.

BACKGROUND: Renal replacement therapy (RRT) transforms the life prospects of young people with established renal failure. However, these treatments can have significant physiological and psychological implications for adolescents as they prepare to transition into adulthood. Health policies increasingly emphasize children and youth's active participation and consultation as users of health services, yet studies infrequently seek their experiences directly. METHODS: Adolescents receiving RRT in a large UK teaching hospital took photographs illustrating the impact of their condition and treatment on their lives. Qualitative photo elicitation interviews were conducted to explore the significance of the images and the young person's experiences. Interviews were analysed using descriptive thematic analysis. RESULTS: Ten young people aged 13-17 years participated. Themes identified were: (1) understanding and acceptance of treatment; (2) living in a non-functioning body; (3) impact upon daily life; (4) sources of support. Young people found treatments challenging and experienced significant impact on relationships and daily routines. Yet, health was prioritized over body image and participants demonstrated great emotional resilience. Young people valued support from family and friends, although were wary of disclosing their condition in case it resulted in being highlighted as different. Young people reported hospital staff as being caring and professional, but their biggest virtue appeared to be their willingness to treat the young people as 'normal'. CONCLUSIONS: Young people engaged readily with the research, and frankly described the impact of RRT on their everyday lives. Service providers must ensure that adolescents' developmental needs are met as traditional tasks of adolescence may lose priority. However, it is also clear that young people's ability to cope with treatments should not be underestimated.

Healthcare staff perceptions towards influenza and potential COVID-19 vaccination in the 2020 pandemic context.

The COVID-19 pandemic generated renewed focus on infectious disease transmission in healthcare settings. This study aimed to evaluate staff perceptions towards influenza vaccination in the COVID-19 context. All healthcare workers within a major UK tertiary referral hospital were invited to answer a survey conducted from September 2nd to 13th, 2020. In all, 593 responses were received across a spectrum of roles; 44% reported they were more likely to get an influenza vaccine this year due to COVID-19; however, 10% felt that an influenza vaccine was less important due to social distancing. Additional questions evaluated intention to receive COVID-19 vaccination. There were substantial differences of opinion between staff groups.

Phenotypic and functional analysis of positive selection in the gamma/delta T cell lineage.

Recent evidence suggests that T cells expressing gamma/delta antigen receptors (T cell receptor [TCR]) are subject to positive selection during development. We have shown that T cells expressing a class I major histocompatibility complex (MHC)-specific gamma/delta TCR transgene (tg) are not positively selected in class I MHC-deficient, beta 2-microglobulin (beta 2m) gene knockout mice (tg+ beta 2m-). In this report, we examine phenotypic and functional parameters of gamma/delta positive selection in this transgenic model system. TCR-gamma/delta tg+ thymocytes of mature surface phenotype (heat stable antigen-, CD5hi) were found in beta 2m+ but not in beta 2m- mice. Moreover, subsets of tg+ thymocytes with the phenotype of activated T cells (interleukin [IL]2R+, CD44hi, or Mel-14lo) were also present only in the beta 2m+ mice. Cyclosporine A, which blocks positive selection of TCR-alpha/beta T cells, also inhibited gamma/delta tg+ T cell development. These results support the idea that positive selection of TCR-gamma/delta requires active TCR-mediated signal transduction. Whereas tg+ beta 2m+ thymocytes produced IL-2 and proliferated when stimulated by alloantigen, TCR engagement of tg+ beta 2m- thymocytes by antigen induced IL-2R expression but was uncoupled from the signal transduction pathway leading to IL-2 production and autocrine proliferation. Overall, these results demonstrate significant parallels between gamma/delta and alpha/beta lineage development, and suggest a general role for TCR signaling in thymic maturation.

Clearance of hepatitis C in chimpanzees is associated with intrahepatic T-cell perforin expression during the late acute phase.

The liver is the primary site of hepatitis C virus (HCV) replication. Therefore, we undertook detailed intrahepatic studies of T-cell dynamics, apoptosis, and gene expression during the acute phase of infection using liver biopsies from chimpanzees that developed persistent infection or spontaneously cleared the virus. We examined more than 40 liver biopsies histologically and quantitatively for T-cell infiltration, hepatocyte apoptosis and perforin expression. These data were correlated with outcome and viral kinetics. We observed intrahepatic T-cell infiltration in both groups of animals with CD8(+) T cells representing the major population. The appearance of T cells was always associated with apoptosis and mild alanine aminotransferase (ALT) elevations. Apoptosis (5-20% of hepatocytes) always occurred prior to serum ALT peak. Quantification of intrahepatic ALT mRNA revealed no upregulation of gene expression confirming that serum ALT increases were due to release of this enzyme from cells. During the late acute phase, cleared animals showed an increased frequency of hepatocyte apoptosis relative to persistently infected animals (P < 0.05). This correlated with a higher intrahepatic CD8(+) T-cell frequency in the cleared group (P < 0.01) with a greater proportion of lymphocytes expressing perforin compared with the persistent group (P < 0.001). All infected animals mounted intrahepatic immune responses during the acute phase, but these were not maintained in frequency or efficacy in persistent infections. There is a reduction in the numbers of intrahepatic T cells during the late acute phase in infections that become persistent with significantly fewer of these cells functional in clearing the virus by killing infected hepatocytes.

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project.

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.

An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus.

The RNA genome of the hepatitis delta virus (HDV) appears to be made up of two parts: a small domain with a high degree of sequence conservation and structural features likely to promote replication; plus a second, larger domain that is less conserved and encodes the delta antigen. This report focuses on one of the several sets of data that have led to the proposal of this model: the existence of a novel structural element in HDV genomic RNA. This structural element lies within the highly conserved domain of HDV RNA and may be related to the local tertiary structure previously mapped to the central conserved region of the plant viroid genome. Both elements occur in regions with no apparent coding capacity and are distinctively responsive to ultraviolet (UV) light. Transcripts containing partial and full-length genomic sequences of HDV readily undergo a UV-induced crosslinking reaction, which establishes a covalent bond between two noncontiguous segments. By locking two segments of the overall structure into place, this crosslink has permitted the unbranched, rodlike model of HDV RNA to be examined and confirmed in the portion of the RNA analyzed. The clustering of the novel tertiary structure and the recently discovered self-cleavage sites into a highly conserved, but apparently noncoding, portion of the genome defines a viroid-like domain in HDV RNA and raises questions about the possible events leading up to the association of free-living RNAs with messenger RNAs and other RNA molecules.

Requirement for positive selection of gamma delta receptor-bearing T cells.

The alpha beta and gamma delta T cell receptors for antigen (TCR) delineate distinct T cell populations. TCR alpha beta-bearing thymocytes must be positively selected by binding of the TCR to major histocompatibility complex (MHC) molecules on thymic epithelium. To examine the requirement for positive selection of TCR gamma delta T cells, mice bearing a class I MHC-specific gamma delta transgene (Tg) were crossed to mice with disrupted beta 2 microglobulin (beta 2M) genes. The Tg+beta 2M- (class I MHC-) offspring had Tg+ thymocytes that did not proliferate to antigen or Tg-specific monoclonal antibody and few peripheral Tg+ cells. This is evidence for positive selection within the gamma delta T cell subset.

Cloned fragment of the hepatitis delta virus RNA genome: sequence and diagnostic application.

Hepatitis delta virus (HDV) is a replication-defective etiological agent of hepatitis that requires hepatitis B virus (HBV) as a helper. A complementary DNA (cDNA) fragment of the RNA genome of HDV was cloned into the plasmid vector pBR322, and the primary nucleotide sequence and predicted protein products of the cDNA fragment were determined. This cloned cDNA fragment has been used as a sensitive radioactive probe for the detection of HDV RNA in the serum of patients with either acute or chronic HDV infections.

Standards for research ethics committees: purpose, problems and the possibilities of other approaches.

Criticism of ethical review of research continues and research ethics committees (RECs) need to demonstrate that they are "fit for purpose" by meeting acknowledged standards of process, debate and outcome. This paper reports a workshop in Warsaw in April 2008, organised by the European Forum for Good Clinical Practice, on the problems of setting standards for RECs in the European Union. Representatives from 27 countries were invited; 16 were represented. Problems identified were the limited and variable resources, difficulties of setting standards for ethical debate and its outcomes and that REC members, as volunteers, may resent the imposition of standards. Other ways to set standards were discussed, including analysis of current multicentre review, collecting REC member reports for review, learning from appeals and feedback from applicants, and use of other regional and national meetings. The place of a central, national board or ethics committee was debated as was the need for collaborating with partners in other fields.

Nosocomial outbreak of measles amongst a highly vaccinated population in an English hospital setting.

In May 2017 a patient attended the emergency department at a hospital in England, with a presumed allergic reaction. He was subsequently diagnosed with measles. There were seven further confirmed cases, five of whom had received two doses of MMR vaccine. This outbreak highlights the importance of not relying on vaccination status to rule out the diagnosis of measles. Epidemiological investigations of this outbreak were particularly challenging due to the highly infectious nature of the measles virus, and prevented full elucidation of either the source of this outbreak or the transmission pathways.

You can love it so much. Heart shape.

Diagnostic imaging can sometimes reveal interesting shapes. In this case we describe a transoesophageal echocardiogram of a mitral valve prolapse in shape of a heart sign, which was successfully repaired.

How can we provide effective training for research ethics committee members? A European assessment.

Training for members of research ethics committees (RECs) varies from state to state in Europe. To follow this up, the European Forum for Good Clinical Practice organised a workshop in March 2007 to explore these issues and look for solutions. This article summarises the discussion, providing ways forward to develop REC training.

Influence of atrial fibrillation on outcome following mitral valve repair.

BACKGROUND: To investigate the outcome of patients in atrial fibrillation (AF) following mitral valve repair, clinical and echocardiographic follow-up was undertaken in 400 consecutive patients who underwent mitral valvuloplasty from 1987 to 1999. METHODS AND RESULTS: The main indications for surgery were degenerative (81.4%), endocarditis (7.1%), rheumatic (6.6%), ischemic (4.6%), and traumatic (0.3%) mitral valve disease. After excluding 6 paced patients and 1 patient in nodal rhythm, we compared the outcomes of 152 patients in AF against 241 patients in sinus rhythm. For patients in AF versus those in sinus rhythm, more AF patients were older (mean age 67.2+/-8.8 versus 61.9+/-11.8 years, respectively; P<0.001), more were assigned to a poorer New York Heart Association (NYHA) class (77.6% versus 66.0% in NYHA III/IV, respectively; P=0.01), and more demonstrated impaired ventricular function (78.9% versus 46.2% with moderate or severe impairment, respectively; P<0.001). For patients in AF versus those in sinus rhythm, there was no difference in 30-day mortality (2.0% versus 2.1%, respectively; P=0.95), repair failure (5.4% versus 3.6%, respectively; P=0.41), stroke (5.4% versus 2.2%, respectively; P=0.11), or endocarditis (2.3% versus 0.9%, respectively; P=0.27) on follow-up at a median of 2.8 years (interquartile range 1.1 to 6.0). On echocardiography, the proportion of patients with mild regurgitation or worse was 13.3% (AF patients) versus 10.8% (patients in sinus rhythm) (P=0.70). Patients in AF versus those in sinus rhythm had lower survival at 3 years (83% versus 93%, respectively) and 5 years (73% versus 88%, respectively). Univariate analysis identified factors affecting survival as AF (P=0.002), age >70 years (P=0.041), and poor ventricular function (P<0.001). However, by use of a multivariate model, only poor ventricular function remained significant (P=0.01). CONCLUSIONS: AF does not affect early outcome or durability of mitral repair. The onset of AF may be indicative of disease progression because of its association with poor left ventricular function.

Transiently elevated diastolic blood pressure is associated with a gender-dependent effect on cardiovascular risk.

We assessed the morbidity and mortality of subjects with transiently elevated diastolic pressure in the General Practice Hypertension Study Group (GPHSG) population. A total of 23 578 patients (aged 18-65 years) from seven UK general practices were screened in 1974 for a diastolic blood pressure (DBP4) of > or = 90 mmHg. Two further readings of DBP4 determined hypertensive (either DBP4 > or = 90 mmHg) or transient hypertensive (both DBP4 < 90 mmHg) status. Transients (n = 850) were matched with normotensive controls (n = 824) and risk ratios calculated over a mean follow-up of 18.7 years. Rescreening was conducted in six of the practices (n = 20 942) after 7.7 years. Male transients had a higher relative hazard for cardiovascular mortality than controls (11.8%, 8.6%, adjusted relative hazard 1.59, P = 0.056). Female transients had a lower relative hazard for cardiovascular mortality than controls (3.6%, 5.4%, adjusted relative hazard 0.39, P = 0.018). In all, 422 patients with transient hypertension were rescreened along with 367 matched controls. Significantly more transients were on antihypertensive treatment compared with their controls (odds ratio (OR) [95% CI]) for both male (4.2 [1.6-11.1]) and female patients (2.4 [1.0-5.56]) and more untreated female transients developed hypertension. Male transients had a higher rates of diabetes mellitus (adj OR = 5.1, P = 0.04) and stroke (adj OR 15.9, P = 0.03). This study has shown that transiently elevated DBP in GPHSG is associated with a significantly higher risk of later hypertension in men and women and of diabetes, stroke and cardiovascular mortality in men. Women with this condition have a significantly lower cardiovascular mortality.

Vocal fold palsy due to plombage for tuberculosis.

A 67-year-old patient, who had previously undergone Lucite ball plombage for pulmonary tuberculosis, presented with a hoarse voice, intermittent stridor and breathlessness. Direct laryngoscopy confirmed a left vocal fold palsy. A left supraclavicular mass became apparent and a computerized tomograph (CT) scan showed that a Lucite ball had migrated into her supraclavicular fossa. Subsequently she developed left arm pain and weakness. The balls were removed surgically, following which her arm symptoms improved but her voice remained unchanged. Migration of implanted material should be considered when new symptoms appear in patients who have undergone plombage treatment.

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

Massive hemothorax due to enlarging arteriovenous fistula in pregnancy.

A 37-year-old woman with hereditary telangiectasia suffered a life-threatening hemothorax due to an enlarging pulmonary arteriovenous malformation in pregnancy. This was treated by emergency right lower lobectomy and excision of arteriovenous malformations in the right middle and upper lobes, with no postoperative complications, and the subsequent delivery of a normal infant. Women with hereditary telangiectasia contemplating pregnancy should be screened for the presence of PAVM to anticipate complications.

Clinical experience and physiologic results with an implantable intratracheal oxygen catheter.

Ten patients with chronic lung disease received an implanted ITOC. Seven patients continue to use their catheters after a mean period of 14.75 months. Four catheters were removed, 2 at 1 month, 1 after 10 months and 1 after 13 months. One patient requested a second catheter. Three patients experienced mucus plug formation; this was transient in two patients, but led to removal of the catheter in the third. To determine the degree of oxygen-saving afforded by the ITOC, SaO2 was measured at rest and during exercise for eight of the ten subjects using a double-blind technique. The calculated oxygen savings were around 40 percent both at rest and during exercise. The ITOCs were well received by the majority of our patients and were shown to produce a useful saving of oxygen which is of benefit to patients using portable systems and those who require high oxygen flow rates.