Concept analysis of recovery in mental illness in young adulthood.

Recovery, as a concept, emerged as a core philosophy of the service user movement that began in the late 1960s and 1970s. Previous reviews on recovery in mental health have presented definitions or a conceptual framework; however, over time it has been open to disparate interpretations. The aim of this paper was to conduct the first concept analysis of mental health recovery in young adulthood within various multidisciplinary contexts. Rodgers's (2000) six-stepped evolutionary method enabled the analysis of recovery's conceptual characteristics, the identification of an exemplar and the proposition of a hypothesis with implications for practice. This analysis has revealed the derivation of the term recovery does not convey its identified conceptual characteristics. Identified attributes include the reawakening of hope, reclaiming a positive self and meaning through personal growth. Antecedents include the disruption of illness, stigmatization, internal inventory and contemplative recovery. Identified consequences include the return to normality, reconstruction of self and active social connection. The new conceptual definition is the reawakening of hope and rediscovery of a positive sense of self through finding meaning and purpose within personal growth and connection using creative self-care coping strategies. This paper reveals an apparent disparity between professional and personal interpretations of recovery. Therefore, the implication for mental health nursing is the congruence of recovery-orientated practice with the process of recovery experienced by young adult service users.

Clinician-performed ultrasound in hemodynamic and cardiac assessment: a synopsis of current indications and limitations.

Accurate hemodynamic and intravascular volume status assessment is essential in the diagnostic and therapeutic management of critically ill patients. Over the last two decades, a number of technological advances were translated into a variety of minimally invasive or non-invasive hemodynamic monitoring modalities. Despite the promise of less invasive technologies, the quality, reliability, reproducibility, and generalizability of resultant hemodynamic and intravascular volume status data have been lacking. Since its formal introduction, ultrasound technology has provided the medical community with a more standardized, higher quality, broadly applicable, and reproducible method of accomplishing the above-mentioned objectives. With the advent of portable, hand-carried devices, the importance of sonography in hemodynamic and volume status assessment became clear. From basic venous collapsibility and global cardiac assessment to more complex tasks such as the assessment of cardiac flow and tissue Doppler signals, the number of real-life indications for sonology continues to increase. This review will provide an outline of the essential ultrasound applications in hemodynamic and volume status assessment, focusing on evidence-based uses and indications.

Exploring the actual and potential role of the primary care nurse in the prevention of cancer: a mixed methods study.

The aim of this study was to investigate the actual and the potential role of the primary care nurse (PCN) in the prevention of cancer. International studies have indicated that a range of strategies can have an impact on the incidence of cancer. Due to their frequent front-line contact with the public, PCNs can play an important role in the primary prevention of cancer. Nonetheless, there is a lack of information on their actual and potential role in cancer prevention. A sequential confirmatory mixed methods approach was used. Postal questionnaires were administered to PCNs [n = 500; 225 returns (response rate 45%)] followed by semi-structured interviews (n = 15). PCNs provided high levels of cancer prevention activities, specifically focusing on smoking cessation, obesity and cervical screening. They considered that their cancer prevention role could be improved through additional practice-based training and more collaborative inter-professional working. They also identified the need for a better understanding of how to change people's attitudes and behaviours regarding cancer prevention. Evidence from this study provide important insights into the potential of the PCN to empower individuals to take responsibility for their own health and make more informed lifestyle choices.

Atom probe tomography analysis of poly(3-alkylthiophene)s.

Pulsed-laser atom-probe tomography is used to compare the field-evaporation mass spectrum and spatial distribution of molecular fragments from various poly(3-alkylthiophene) films deposited on sharpened aluminium specimen carriers using two different deposition methods. Films deposited via a modified solution-cast methodology yield small fragments with a uniform structural morphology whereas films deposited via an electrospray ionization methodology yield a wide range of fragments with a very non-uniform structural morphology. The main field-evaporated chemical species identified for both deposition types were, in order of typical relative abundance, C(2)H(5) (+), CH(3) (+), C(2)H(4) (+), followed by C(3)H(7,8) (+)/SC(+) and SCH(+). Thick electrospray depositions allowed investigation of the influence of laser-pulse energy on the analysis. Evidence is presented supporting the presence of a critical laser-pulse energy whereby changes in film morphology are signalled by the appearance of a new mass fragment at 190 Da.

Attitudes to cancer and cancer prevention: what do people aged 35-54 years think?

The aim of this study was to explore the knowledge, attitudes and behaviours of people in mid-life towards cancer prevention. The study was undertaken in Northern Ireland between 2003 and 2007. This was a mixed methods study using a sequential exploratory design. The theoretical framework was the Theory of Planned Behaviour and the methodology was based on Sutton's framework. There were three methodological stages in the study using focus groups, a large cross-sectional survey and a volunteer sample survey. This paper focuses on the findings of the cross-sectional survey relating to the attitudes of people in mid-life towards cancer and cancer prevention. Findings are considered in relation to the respondents' level of knowledge, age, gender, level of educational attainment and socio-economic status. Evidence from this study shows that attitudes towards cancer and cancer prevention are associated significantly with level of knowledge about cancer, gender, socio-economic status and level of educational attainment. In conclusion, the evidence from this study shows that men, those with a lower level of education, those with a lower level of knowledge and those in a lower socio-economic group were more likely to hold negative attitudes about cancer and cancer prevention.

The mutation spectrum associated with type 3 von Willebrand disease in a cohort of patients from the north west of England.

Type 3 von Willebrand disease (VWD) is a severe autosomal recessive inherited bleeding disorder. In affected individuals the underlying von Willebrand factor gene (VWF) mutations frequently remain uncharacterized. The aim of this study was to investigate the molecular basis of type 3 VWD in patients (11 Caucasians and 9 of Asian origin) attending the haemophilia centres at Central Manchester NHS Trust. A combination of DNA sequencing of VWF genomic and complementary DNA was performed to identify mutations in the patient cohort. Fifteen different VWF mutations were identified at the genomic DNA level: two gene conversion events, three nonsense, three frameshift, one missense, two splice site, one insertion-deletion and three deletion mutations. Homozygosity or compound heterozygosity for mutations was present in 15 of the 20 patients. In the remaining five individuals, heterozygosity for a single VWF mutation was identified in four cases and one patient had no detectable VWF mutation. Analysis of platelet-derived VWF RNA from these five individuals revealed heterozygosity for a deletion of exons 4 and 5 in four cases. The remaining patient was heterozygous for a three base deletion which had already been identified at the DNA level. Overall the observed VWF genotype explained the phenotype in 18 of the 20 patients investigated. In genetic studies in type 3 VWD, if VWF mutations are not detected at the DNA level, RNA analysis should be performed to search for intronic mutations, heterozygous deletions or aberrant splicing/post-transcriptional events. However, this may still not explain all cases of previously phenotypically diagnosed type 3 VWD.

The molecular analysis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organisation Haemophilia Genetics Laboratory Network.

von Willebrand disease (VWD) is a common autosomally inherited bleeding disorder associated with mucosal or trauma-related bleeding in affected individuals. VWD results from a quantitative or qualitative deficiency of von Willebrand factor (VWF), a glycoprotein that is essential for primary haemostasis and that carries and protects coagulation factor VIII (FVIII) in the circulation. Through characterization of the phenotype and identification of mutations in the VWF gene in patients with VWD, understanding of the genetics and biochemistry of VWF and VWD has advanced considerably. The importance of specific regions of VWF for its interaction with other components of the vasculature has been revealed, and this has facilitated the formal classification of VWD into three subtypes based upon quantitative (types 1 and 3) and qualitative (type 2) deficiency of VWF. The underlying genetic lesions and associated molecular pathology have been identified in many cases of the qualitative type 2 VWD variants (2A, 2B, 2M, 2N) and in the severe quantitative deficiency, type 3 VWD. However in the partial quantitative deficiency, type 1 VWD, the picture is less clear: there is a variable relationship between plasma levels of VWF and bleeding, there is incomplete penetrance and variable expressivity within affected families, the causative molecular defect is unknown in a substantial number of cases, and even in those cases where the causative mutation is known, the associated molecular pathology is not necessarily understood. This guideline aims to provide a framework for best laboratory practice for the genetic diagnosis of VWD, based upon current knowledge and understanding.

C1584 in von Willebrand factor is necessary for enhanced proteolysis by ADAMTS13 in vitro.

The cysteine variant of the amino acid change tyrosine/cysteine 1584 (Y/C1584) in von Willebrand factor (VWF) has previously been shown to cosegregate with increased susceptibility of VWF to proteolysis by ADAMTS13. It is not known whether C1584 itself confers increased proteolysis or is linked to a causative change elsewhere in VWF. To address whether C1584 underlies enhanced susceptibility of VWF to ADAMTS13-mediated proteolysis, a single family comprising two heterozygous Y/C1584 individuals and four homozygous Y/Y1584 individuals was investigated. The essential regions of the VWF gene were sequenced in all six individuals and ADAMTS13-mediated proteolysis of plasma VWF was assessed for each individual. Comparison of the VWF coding sequences for the Y/C1584 individuals with those for the Y/Y1584 individuals revealed that two amino acid variants were unique to the heterozygotes: R484 and C1584. The plasma VWF of the two heterozygotes showed increased susceptibility to proteolysis in vitro compared with that of the four homozygotes. In the present study we demonstrate that R484, in the absence of C1584, does not influence VWF proteolysis. Enhanced proteolysis occurred only in the presence of Cys1584. Thus, Cys1584 is necessary for increased susceptibility of VWF to proteolysis by ADAMTS13.

Clinical supervision for mental health nurses in Northern Ireland: formulating best practice guidelines.

Nurses work in a constantly challenging and changing environment. Within this context, there is a continuing need for support. Such support will help increase morale, decrease strain and burnout, and encourage self-awareness and self-expression. Clinical supervision address all these issues and enhances the quality of care for patients. While clinical supervision is a policy imperative in Northern Ireland, it was clear that there were problems in its implementation in mental health nursing. The aim of this project was to explore ways to make clinical supervision available to all mental health nurses and to improve and evaluate their contribution to patient care. The research team undertook a comprehensive literature review and a baseline survey of relevant stakeholders. Results represent the outcome of the group work. They will assist healthcare providers to develop local policies and procedures on clinical supervision for practising mental health nurses.

Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages.

Meiosis pairs and segregates homologous chromosomes and thereby forms haploid germ cells to compensate the genome doubling at fertilization. Homologue pairing in many eukaryotic species depends on formation of DNA double strand breaks (DSBs) during early prophase I when telomeres begin to cluster at the nuclear periphery (bouquet stage). By fluorescence in situ hybridization criteria, we observe that mid-preleptotene and bouquet stage frequencies are altered in male mice deficient for proteins required for recombination, ubiquitin conjugation and telomere length control. The generally low frequencies of mid-preleptotene spermatocytes were significantly increased in male mice lacking recombination proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice with only one copy of the telomere length regulator Terf1. The bouquet stage was significantly enriched in Atm(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-), Terf1(+/-) and Hr6b(-/-) spermatogenesis, but not in mice lacking recombination proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies. A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit defect. Insignificant changes of bouquet frequencies in mice with defects in early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM-specific influence on bouquet stage duration. Altogether, it appears that several pathways influence telomere dynamics in mammalian meiosis.

Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation.

Homologous recombination is essential for accurate chromosome segregation during meiosis in most sexual organisms. Meiotic recombination is initiated by the formation of DSBs (DNA double-strand breaks) made by the Spo11 protein. We review here recent findings pertaining to protein-protein interactions important for DSB formation, the mechanism of an early step in the processing of Spo11-generated DSBs, and regulation of DSB formation by protein kinases.

The molecular analysis of haemophilia B: a guideline from the UK haemophilia centre doctors' organization haemophilia genetics laboratory network.

Haemophilia B is one of the most common inherited bleeding disorders and has a well understood pathophysiology. Our understanding of the molecular genetics of the disease has allowed the development of comprehensive carrier and prenatal diagnosis for this single gene disorder. Continuing technological developments improve our ability to provide genetic analysis in a rapid and cost-effective manner. This guideline aims to provide advice on current best laboratory practice when approaching genetic diagnosis of haemophilia B.

The molecular analysis of haemophilia A: a guideline from the UK haemophilia centre doctors' organization haemophilia genetics laboratory network.

Haemophilia A is a common inherited bleeding disorder that has a well-understood pathophysiology. Our understanding of the molecular genetics of the disease has allowed the development of comprehensive carrier and prenatal diagnosis for this single gene defect. Continuing technological developments improve our ability to provide genetic analysis in a rapid and cost effective manner. This guideline aims to provide advice on current best laboratory practice when approaching genetic diagnosis of haemophilia A.

A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency.

Factor XI (FXI) deficiency is a mild bleeding disorder that is particularly common in Ashkenazi Jews, but has been reported in all populations. In Jews, two FXI gene (F11) mutations (a stop codon in exon 5, E117X, type II, and a point mutation in exon 9, F283L, type III) are particularly common, but in other populations a variety of different mutations have been described. In the Basque region of France one mutation, C38R in exon 3, was found in eight of 12 families studied, haplotype analysis suggesting a founder effect. In the course of screening 78 unrelated individuals (including 15 Jewish and 12 Asian) we have found 10 Caucasian non-Jewish patients with the mutation C128X in exon 5. Individuals were investigated because of a personal or family history of bleeding, or finding a prolonged activated partial thromboplastin time. Individuals negative for the type II and type III mutations were screened by a combination of SSCP and heteroduplex analysis. The C128X mutation was found in 10 families (one previously described). Among three individuals with severe FXI deficiency, one was homozygous for the C128X mutation, and two were compound heterozygotes for the C128X and another mutation; other individuals were carriers of the C128X mutation. This is a nonsense mutation producing a truncated protein; individuals have FXI antigen levels concordant with FXI coagulant activity. Haplotype analysis of 11 families, including a further kindred previously reported from the USA, but which originally came from the UK (in which the index patient was homozygous for C128X), suggests a founder effect.

The molecular biology of von Willebrand disease.

von Willebrand disease (VWD) is a common autosomally inherited bleeding disorder associated with mucosal or trauma-related bleeding in affected individuals. VWD results from either a quantitative or qualitative deficiency of von Willebrand factor (VWF)--a glycoprotein with essential roles in primary haemostasis and as a carrier of coagulation factor VIII (FVIII) in the circulation. In recent years the identification of mutations in the VWF gene in patients with VWD has improved our understanding of the structure and function of the VWF protein, and has illustrated the importance of specific regions of VWF for its interaction with other components of the vasculature. The underlying genetic lesions and associated molecular pathology have been identified in many cases of type 2A, type 2B, type 2M, type 2N and type 3 VWD. However in the most common variant, type 1 VWD, the causative molecular defect is unknown in the large majority of cases. In the absence of an understanding of the molecular pathology underlying type 1 VWD, precise diagnosis and classification of this common disorder remains problematic.

Mechanism and control of meiotic recombination initiation.

Homologous recombination is essential during meiosis in most sexually reproducing organisms. In budding yeast, and most likely in other organisms as well, meiotic recombination proceeds via the formation and repair of DNA double-strand breaks (DSBs). These breaks appear to be formed by the Spo11 protein, with assistance from a large number of other gene products, by a topoisomerase-like transesterase mechanism. Recent studies in fission yeast, multicellular fungi, flies, worms, plants, and mammals indicate that the role of Spo11 in meiotic recombination initiation is highly conserved. This chapter reviews the properties of Spo11 and the other gene products required for meiotic DSB formation in a number of organisms and discusses ways in which recombination initiation is coordinated with other events occurring in the meiotic cell.

Recombinational DNA double-strand breaks in mice precede synapsis.

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.

Meiotic recombination: Making and breaking go hand in hand.

Accurate segregation of homologous chromosomes at the first meiotic division requires the tight coordination of DNA replication, homologous recombination and chromosome organization. Recent studies suggest that the initiation of meiotic recombination is mechanistically coupled to premeiotic DNA replication.