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Moral injury is a relatively new, but increasingly studied, construct in the field of mental health, particularly in relation to current and ex-serving military personnel. Moral injury refers to the enduring psychosocial, spiritual or ethical harms that can result from exposure to high-stakes events that strongly clash with one’s moral beliefs. There is a pressing need for further research to advance understanding of the nature of moral injury; its relationship to mental disorders such as posttraumatic stress disorder and depression; triggering events and underpinning mechanisms; and prevalence, prevention and treatment. In the meantime, military leaders have an immediate need for guidance on how moral injury should be addressed and, where possible, prevented. Such guidance should be theoretically sound, evidence-informed and ethically responsible. Further, the implementation of any practice change based on the guidance should contribute to the advancement of science through robust evaluation. This paper draws together current research on moral injury, best-practice approaches in the adjacent field of psychological resilience, and principles of effective implementation and evaluation. This research is combined with the military and veteran mental health expertise of the authors to provide guidance on the design, implementation and evaluation of moral injury interventions in the military. The paper discusses relevant training in military ethical practice, as well as the key roles leaders have in creating cohesive teams and having frank discussions about the moral and ethical challenges that military personnel face.

IntroductionEvidence is growing regarding the impact of potentially morally injurious events (PMIEs) on mental health; yet how moral injury may affect an individual’s occupational and familial functioning remains poorly understood.MethodThirty male veterans who reported exposure to either traumatic or morally injurious events and 15 clinicians were recruited for semi-structured qualitative interviews.ResultsWhile many veterans experienced psychological distress postevent, those who experienced PMIEs especially reported social withdrawal and engagement in aggressive, risk-taking behaviours. This was highly distressing for family members and created a tense, volatile home and workplace environment that was difficult for others to navigate. Following PMIEs, employment could be used as a cognitive avoidance strategy or as a means to atone for transgressive acts. In cases of moral injury, clinicians considered that targeted support for spouses and accessible guidance to help children to better understand how their military parent may be feeling would be beneficial.ConclusionsThis study provides some of the first evidence of the pervasive negative impact of PMIEs on veterans’ familial and occupational functioning. These findings highlight the need to comprehensively screen for the impact of moral injury on daily functioning in future studies that goes beyond just an assessment of psychological symptoms.

AbstractAimsPolice employees may experience high levels of stress due to the challenging nature of their work which can then lead to sickness absence. To date, there has been limited research on sickness absence in the police. This exploratory analysis investigated sickness absence in UK police employees.MethodsSecondary data analyses were conducted using data from the Airwave Health Monitoring Study (2006–2015). Past year sickness absence was self-reported and categorised as none, low (1–5 days), moderate (6–19 days) and long-term sickness absence (LTSA, 20 or more days). Descriptive statistics and multinomial logistic regressions were used to examine sickness absence and exploratory associations with sociodemographic factors, occupational stressors, health risk behaviours, and mental health outcomes, controlling for rank, gender and age.ResultsFrom a sample of 40,343 police staff and police officers, forty-six per cent had no sickness absence within the previous year, 33% had a low amount, 13% a moderate amount and 8% were on LTSA. The groups that were more likely to take sick leave were women, non-uniformed police staff, divorced or separated, smokers and those with three or more general practitioner consultations in the past year, poorer mental health, low job satisfaction and high job strain.ConclusionsThe study highlights the groups of police employees who may be more likely to take sick leave and is unique in its use of a large cohort of police employees. The findings emphasise the importance of considering possible modifiable factors that may contribute to sickness absence in UK police forces.

The outbreak of COVID-19 and the subsequent pandemic brought unprecedented worldwide challenges born out of a rapidly escalating health and economic crisis. From emergency planners to healthcare workers on the front line, and everyone in between, the pandemic, and the uncertainty surrounding it, was likely to become a significant stressor, one with no immediate solution but with the potential to cause enduring distress beyond its conclusion. The UK Defence Medical Services recognised the need to provide an evidence-based programme of care intended to support personnel transitioning from assisting the national response back to normal duties. This was informed by a narrative review that targeted literature exploring strategies for supporting the mental health and well-being of healthcare workers during 21st-century infectious disease outbreaks. The literature identified the experiences most likely to cause enduring distress, which comprised morally challenging decisions, vulnerability, death and suffering, professional and personal challenges, and expectations. The opportunity to find meaning in these experiences, by discussing them with peers who share a contextual understanding, is important to limit the longer-term psychosocial impact of such events. This paper will discuss the design considerations and planned implementation strategy of the Recovery, Readjustment and Reintegration Programme to limit the incidence of distress or longer-term mental ill health among military personnel.

IntroductionPredeployment stress management/mental health training is routinely delivered in an effort to mitigate potential adverse psychological effects. Little is known about the effectiveness of such interventions.MethodsA systematic literature review explored research outcomes related to this subject, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. An electronic database search using key terms identified studies published between January 2007 and March 2019. Comprehensive inclusion/exclusion criteria were applied and study quality was appraised by two reviewers using 12 criteria adapted from the Critical Appraisal Skills Programme (CASP) checklist. Papers were excluded if they were allocated CASP scores ≤10 out of 24.Results2003 references were identified; 15 papers fulfilled inclusion criteria and quality threshold requirements. Included studies were randomised controlled trial design (n=8), quasi-experimental (n=5), case report (n=1) and cross-sectional (n=1). Duration of follow-up assessment varied from immediately postintervention to 24 months. The included studies were heterogeneous so clear recommendations relating to predeployment training for military personnel could not be made. Although somewhat disparate, predeployment interventions shared the aim of promoting prior to, during and after deployment health and well-being. Social benefits such as improved cohesion and improved stress management skills were identified in some studies, although substantial mental health and well-being benefits were not found.ConclusionsEvidence for the effectiveness of predeployment psychological interventions is scant. Every attempt should be made to use methods and measures to facilitate comparisons across studies, to attempt a longer follow-up timescale and to clarify key trainer characteristics.

IntroductionResearch suggests that moral injury (MI) in US veterans is associated with poor psychological outcomes and disruption in functioning. However, little is known about how MI may impact UK Armed Forces (AF) veterans. This study aimed to explore the impact of MI on veteran psychological well-being and functioning.MethodsSix veterans identified as having had exposure to MI and four clinicians who treated veterans with MI were recruited from a UK charitable organisation which provides psychological care for veterans. Data were analysed using thematic analysis.ResultsMI was perceived to cause substantial psychological distress in this sample. Our data suggest that some veterans held extremely negative self-appraisals which appeared to contribute towards and maintain their distress. Issues relating to spirituality following MI were thought to be infrequent; however, a loss of faith was perceived by clinicians to be more common in morally injured veterans than heightened spiritual/religious views. Several difficulties relating to employment were described, including increased trouble coping with occupational stress and authority figures. Interpersonal difficulties were frequently reported, with withdrawal from others often leading to relationship breakdown with spouses and children.ConclusionThis study provides some of the first evidence of the impact of MI on UK AF veterans’ psychological, spiritual, social and day-to-day functioning all of which would pose challenges to clinicians aiming to manage such difficulties. These findings highlight several gaps in existing care provision for morally injured veterans, including addressing issues related to spirituality, employment and family functioning, which could ultimately improve veteran well-being.

As disasters become increasingly prevalent, and reported on, a wealth of literature on post-disaster mental health has been published. Most published evidence focuses on symptoms of mental health problems (such as post-traumatic stress disorder, depression and anxiety) and psychosocial factors increasing the risk of such symptoms. However, a recent shift in the literature has moved to exploring resilience and the absence of adverse lasting mental health effects following a disaster. This paper undertakes a qualitative review of the literature to explore factors affecting psychological resilience, as well as the potential positive impact of experiencing a disaster (post-traumatic growth) by examining the literature on employees in disaster-exposed organisations. We identify several protective factors: training, experience, and perceived (personal) competence; social support; and effective coping strategies. Post-traumatic growth frequently appeared to occur at both personal and professional levels for those rescue staff after a disaster, giving employees a greater appreciation of life and their relationships, enhancing their self-esteem and providing a sense of accomplishment and better understanding of their work. Implications, in terms of how to build a resilient workforce, are discussed.

Morally injurious incidents may present ethical or legal quandaries, yet how military or civilian clinicians should manage such disclosures is poorly understood. Individuals who experience moral injury may be reluctant to seek help due to concerns about the legal ramifications of disclosure. Guidance on breaching patient confidentiality differs by regulatory body but also by profession, geography and context. As moral injury continues to become recognised in clinical practice, in the military and elsewhere, clarity is needed regarding best practice in managing moral injury cases and the dilemmas they present.

BackgroundGenetic research may have therapeutic value for mental and physical disorders and could have an indicative or preventative capacity. Little is known about the extent, form and utility of military-specific genetic research.MethodA systematic review was conducted to evaluate existing genetic well-being studies of service personnel. The review specifically aimed to ascertain the current state of knowledge and feasibility of using genetics to aid recruitment and health management within military populations. Databases searched included MEDLINE, Embase, PsycINFO and Web of Science for relevant studies. Papers were rated using a genetics-specific quality assessment framework.ResultsTen papers were included within the final review, with seven mental-health-focused and three physical-health-focused genetic studies found within military populations. Eight papers considered candidate genes, one gene expression and one study was an outline of a future study of significant interest. Genetic commonalties were derived to yield shared physiological pathways. The 10 reviewed papers revealed moderate quality based on quality assessment.ConclusionsCurrent genetic research within military populations is limited. Further studies on genetics, cost effectiveness, ethics and continual monitoring need to be explored before considering any movement toward clinical translation.

IntroductionFor the purposes of this review, caregivers are individuals who provide care that is typically unpaid and usually takes place at home. This systematic review aims to identify burden among spouses/partners caring for wounded, injured or sick military personnel and the factors associated with caregiver burden.MethodsA systematic review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Five electronic databases and relevant websites were searched. Two reviewers appraised the quality of the studies and carried out data extraction.ResultsTen original papers were identified, of which eight were quantitative studies and two were qualitative. These papers highlighted the potential negative impact caregiving can have on spouses/partners and also some of the positive aspects of caring that can strengthen intimate relationships.ConclusionsCaring for an injured or ill military spouse or partner is a difficult task, compounded by the complexity of dealing with potentially both their physical and mental health problems. However, research has also identified some positive aspects of caring that can strengthen intimate relationships.

AimCurrently, there is no research available on the experiences of spouses providing informal care to wounded, injured or sick (WIS) UK military personnel. The aim of this study was to fill this gap by investigating the relationship experiences of non-military partners caring for WIS UK military personnel.MethodsSpouses of WIS military personnel (n=25) completed telephone interviews with the research team. The data were transcribed and analysed using thematic analysis. The transcripts were cross-coded and checked for inter-rater reliability.ResultsSix major themes were identified: (1) communication between couples, (2) adverse family environment, (3) reintegration, (4) intimacy, (5) financial uncertainty and (6) transition from partner to caregiver.ConclusionsPartners caring for injured/ill military personnel appear to be at risk of experiencing personal distress caused by impaired relationship functioning, which may lead to diminished physical and mental well-being. Partners of WIS military personnel experience significant levels of distress and burden associated with caregiving in the form of arguments with the military partner, problems in reintegration and a lack of physical and emotional intimacy.

Organisations including the United Kingdom Armed Forces should seek to implement mental health interventions to increase the psychological well-being of their workforce. This editorial briefly presents ten key principles that military forces should consider before implementing such interventions. These include job-focused training; evaluating interventions; the use of internal versus external training providers; the role of leaders; unit cohesion, single versus multiple session psychological interventions; not overgeneralising the applicability of interventions; the need for repeated skills practice; raising awareness and the fallibility of screening.

ObjectiveFear et alidentified a small but significant increase in probable post-traumatic stress disorder (PTSD) in UK military personnel from around 3% in first year post deployment to around 6% by year 5. As yet it is not clear what factors are linked to the increase in probable PTSD, and therefore, serial measurement of poor mental health would be helpful.MethodRates of mental ill health among UK service personnel were compared upon deployment completion and at follow-up and identified factors associated with maladjustment.ResultsPoor mental health symptomatology increased from baseline to follow-up, PTSD symptoms and related functional impairment increased significantly. Poor baseline mental health was predictive of transition and family relationship difficulties.ConclusionsThe results are discussed in relation to encouraging recognition and reporting of symptoms among personnel and their social networks.

IntroductionUK military research suggests that there is a significant link between current psychological symptoms, mental health stigmatisation and perceived barriers to care (stigma/BTC). Few studies have explored the construct of stigma/BTC in depth amongst deployed UK military personnel.MethodThree survey datasets containing a stigma/BTC scale obtained during UK deployments to Iraq and Afghanistan were combined (n=3405 personnel). Principal component analysis was used to identify the key components of stigma/BTC. The relationship between psychological symptoms, the stigma/BTC components and help seeking were examined.ResultsTwo components were identified: ‘potential loss of personal military credibility and trust’ (stigma Component 1, five items, 49.4% total model variance) and ‘negative perceptions of mental health services and barriers to help seeking’ (Component 2, six items, 11.2% total model variance). Component 1 was endorsed by 37.8% and Component 2 by 9.4% of personnel. Component 1 was associated with both assessed and subjective mental health, medical appointments and admission to hospital. Stigma Component 2 was associated with subjective and assessed mental health but not with medical appointments. Neither component was associated with help-seeking for subjective psycho-social problems.ConclusionsPotential loss of credibility and trust appeared to be associated with help-seeking for medical reasons but not for help-seeking for subjective psychosocial problems. Those experiencing psychological symptoms appeared to minimise the effects of stigma by seeking out a socially acceptable route into care, such as the medical consultation, whereas those who experienced a subjective mental health problem appeared willing to seek help from any source.

IntroductionClinical assessment is an essential but potentially time-consuming component of mental healthcare provision. The Threshold Assessment Grid (TAG) is a brief structured assessment tool which is applied to written referrals with the aim of identifying the severity of mental illness and suitability for further psychological treatment by assessing perceived risk, safety concerns and clinical factors.MethodThe TAG criteria were used to structure a brief TAG-triage face-to-face assessment. As the use of triage has not been evaluated within a military occupational mental health service, differences in clinical and occupational outcomes were compared following either standard face-to-face assessment or receipt of TAG-triage interview among members of the UK Armed Forces who were referred for mental health assessment. During a period of service development, 56.6% of patients referred to a military mental health team received TAG-triage assessment (n=419) and 43.5% were assessed as usual (n=323).ResultsThere were no significant differences in rank, age, sex and Service background between patients allocated to the two forms of assessment. Patients presenting following acts of deliberate self-harm were as likely to receive TAG-triage as they were to undergo standard assessment, suggesting that clinicians were willing to use TAG-triage for more challenging cases. Patients receiving TAG-triage were as likely to receive further therapy and be allocated a clinical diagnosis as those undergoing standard assessment. Short-term and longer-term occupational outcomes following discharge from care, represented by medical fitness to carry out one's military role, were similar among the TAG-triage and standard assessment groups.ConclusionTAG-triage appeared to offer a viable alternative to standard face-to-face mental health assessment and could promote more efficient use of clinical time.

A pilot study to assess the practicality of introducing an enhanced mental health assessment (EMHA) into all routine and discharge medicals of the UK Armed Forces in order to facilitate treatment prior to and on return to civilian life.

The recent conflicts in Iraq and Afghanistan have attracted considerable political and media interest in the mental health of UK military personnel. As a result of the close operational collaboration between US and UK forces, there have inevitably been many comparisons drawn between the mental health status of the two forces. Considerable research activity suggests that the mental health of UK forces appear to have remained relatively resilient in spite of their considerable exposure to traumatic events; one stark exception to this is the high rates of alcohol misuse which seem to be related to deployment. This paper explores the recently published literature relating to UK military forces and attempts to draw conclusions about the reasons for the apparent resilience shown by the majority of the regular forces.

The role of elastic recoil in producing intraventricular pressure gradients (IVPG) is well known. The influence of other physiologic variables however remains unclear. The aim of this study was therefore to investigate in a combined canine and hydraulic model experiment the role of regional differences in left ventricle (LV) relaxation in producing IVPG. In the canine model, the LV relaxation time constant (τ) was significantly shorter at the apex comparedto the base of the LV at baseline, during isoproterenol infusion and during esmolol infusion. IVPG rose significantly with isoproterenol and fell with esmolol compared to baseline values. Multivariate analysis demonstrated both Δτ and τ to contribute significantly to predicting IVPG. These findings were supported by similar measurements in a hydraulic model, which showed IVPG to be closely related to Δτ. In addition, the in vitro results suggested that higher LV compliance is associated with increased IVPG. This study demonstrated that in addition to elastic recoil, regional relaxation differences significantly impact IVPG. Assessment of IVPG, now available noninvasively, could provide useful clinical insight into cardiac ischemia and diastolic dysfunction.

To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes (ECO:RI and c-fos) implicated in the induction of genomic instability. Expression of the transgenes was restricted to prostate epithelial cells by coupling them to the tissue-specific, hormonally regulated probasin promoter (PB). The effects of transgene expression were examined histologically in prostate sections at time points taken from 4 to 24 months of age. The progressive presence of regions of mild-to-severe hyperplasia, low- and high-grade prostatic intra-epithelial neoplasia, and well-differentiated adenocarcinoma was observed in both PBECO:RI lines but no significant pathology was detected in the PBfos line. Prostate tissue of PBECO:RI mice was examined for expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67 are elevated and correlate with the severity of the prostatic lesions. Overall, pre-neoplastic and neoplastic stages represented in the PBECO:RI model showed similarity to corresponding early stages of the human disease. This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease.

Follicle-stimulating hormone (FSH; follitropin) is a pituitary glycoprotein composed of two post-translationally modified subunits, which must properly assemble to be biologically active. FSH has been difficult to purify and to obtain in quantities sufficient for detailed biochemical studies. We have targeted FSH expression to the mammary gland of transgenic mice by using cDNAs encoding the bovine alpha and FSH beta subunits and a modified rat beta-casein gene-based expression system. Lines of bigenic mice expressing both subunits have been generated either by coinjection of the subunit transgenes or by mating mice that acquired and expressed transgenes encoding an individual subunit. Up to 60 international units (15 micrograms) of biologically active FSH per ml was detected in the milk of the bigenic mice. These lines provide a model system for studying the post-transcriptional mechanisms that effect the expression and secretion of this heterodimeric hormone.

Persons who received measles vaccine between 12 and 14 months of age have been found to be at increased risk of measles compared with those vaccinated at greater than or equal to 15 months of age. Because of this, in 1987 the Immunization Practices Advisory Committee of the US Public Health Service recommended that, during measles outbreaks, revaccination of persons vaccinated at 12-14 months of age be considered. During a school-based outbreak in New Mexico in 1987, the authors evaluated the effect of a mandatory revaccination policy in affected schools. Before the effect of revaccination, the overall attack rate in persons vaccinated at greater than or equal to 12 months of age was 4.1 cases/1,000 students; afterward, the risk was significantly reduced by 73%, to 1.1/1,000 students. The attack rate among students targeted for revaccination declined 100%, compared with 41% among those not revaccinated. Overall, attack rates were significantly lower in schools conducting revaccination early compared with schools holding later revaccination. In a retrospective cohort study of single-dose vaccines in one school, age at vaccination was not associated with risk of disease; however, persons vaccinated greater than or equal to 10 years before the outbreak were at increased risk, independently of age at vaccination. Revaccination of persons whose most recent vaccination was between 12 and 14 months of age appeared to control transmission in this outbreak. Further studies are needed to confirm these observations and to evaluate the effect of other revaccination efforts during outbreaks.

Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.

MVL2 virus was purified from culture supernatants of infected Acholeplasma laidlawii cells by differential centrifugation, followed by velocity centrifugation in sucrose gradients. The purified virus contained 0.08 to 0.1 mumol of lipid phosphorous per ml of viral protein. Thin-layer chromatography of viral lipids revealed the presence of phospho-, glyco-, and phosphoglycolipids identical with those found in the host cell membrane, but the relative amount of phosphatidylglycerol was much lower than that in the virus. The fatty acid composition of lipids incorporated into the virus included lipids synthesized before and after infection. The freedom of motion of spin-labeled fatty acids in MVL2 depended markedly on temperature and on the position of the nitroxide group on the hydrocarbon chain of the probe, suggesting that the local environment of the probe has the properties of a lipid bilayer. Nevertheless, the lipid hydrocarbon chains in MVL2 appear to be less mobile than those in membranes of the host cells. Polyacrylamide gel electrophoresis of purified MVL2 revealed four major and about five minor polypeptide bands. None of the polypeptide bands gave a positive periodic acid-Schiff reaction. Lactoperoxidase-mediated iodination, followed by proteolytic digestion of intact MVL2 particles, revealed that at least two major polypeptides are localized on the external surface of the viral envelope.

The deoxypyrimidine nucleoside analog 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodocytosine (FIAC) is a potent and selective inhibitor of herpes simplex virus type 1 in vitro (C. Lopez, K. A. Watanabe, and J. J. Fox, Antimicrob. Agents Chemother. 17:803-806, 1980). Isopycnographic analysis demonstrated that 1 microM FIAC inhibited herpes simplex virus DNA replication by more than 95% but inhibited cellular DNA replication by only 32%. Mutant herpes simplex virus type 1 selected resistant to FIAC displayed linked resistance to other nucleoside analogs, including arabinosylthymine and acyclovir. Lysates derived from Vero cells infected with FIAC-resistant virus showed markedly lower levels of thymidine kinase activity and were unable to phosphorylate selectively arabinosylthymine or FIAC, in contrast to lysates from cells infected with wild-type herpes simplex virus type 1. Finally, drug-resistant virus displayed a 6,000-fold decrease in pathogenicity when inoculated intraperitoneally into genetically susceptible A/J mice. These results indicate that resistance to deoxypyrimidine nucleoside analogs is due, at least in part, to alterations in viral thymidine kinase and is accompanied by decreased pathogenicity in vivo.

We characterized the in vivo transcripts of two Cellulomonas fimi genes, the cenA gene, which encodes an extracellular endo-beta-1,4-glucanase (EC 3.2.1.4) and the cex gene, which encodes an extracellular exo-beta-1,4-glucanase (EC 3.2.1.91). By Northern blot analysis, cenA mRNA was detected in C. fimi RNA preparations from glycerol- and carboxymethyl cellulose-grown cells but not from glucose-grown cells. In contrast, cex mRNA was detected only in the preparations from carboxymethyl cellulose-grown cells. Therefore, the transcription of these genes is subject to regulation by the carbon source provided to C. fimi. By nuclease S1 protection studies with unique 5'-labeled DNA probes and C. fimi RNA isolated in vivo, 5' termini were found 51 and 62 bases before the cenA translational initiation codon and 28 bases before the cex translational initiation codon. S1 mapping with unlabeled DNA probes and C. fimi RNA which had been isolated in vivo but which had been 5' labeled in vitro with guanylyltransferase and [alpha-32P]GTP confirmed that true transcription initiation sites for cenA and cex mRNA had been identified. Comparative analysis of the DNA sequences immediately upstream of the initiation sites of the cenA and cex mRNAs revealed a 30-base-pair region where these two sequences display at least 66% homology. S1 mapping was also used to locate the 3' termini of the cenA and cex transcripts. Three 3' termini were found for cenA messages, whereas only one 3' terminus was identified for cex mRNA. The transcripts of both genes terminate in regions where their corresponding DNA sequences contain inverted repeats.

The DNA sequence was determined for the cloned Agrobacterium sp. strain ATCC 21400 beta-glucosidase gene, abg. High-resolution nuclease S1 protection studies were used to map the abg mRNA 5' and 3' termini. A putative abg promoter was identified whose sequence shows similarities to the consensus promoter of Escherichia coli and with the nif promoter regions of Klebsiella. The abg coding sequence was 1,374 nucleotides long. The molecular weight of the enzyme, based on the predicted amino acid sequence, was 51,000. The observed Mr was 50,000 to 52,000. A region of deduced protein sequence was homologous to a region from two other beta-glucosidase sequences. This region of homology contained a putative active site by analogy with the active site of hen egg white lysozyme.

We characterized the in vivo transcription of the Cellulomonas fimi cenB gene, which encodes an extracellular endo-beta-1,4-glucanase (EC 3.2.1.4). By Northern blot (RNA blot) analysis, cenB mRNA was detected in C. fimi RNA preparations from glycerol-, glucose-, and carboxymethyl cellulose (CMC)-grown cells. The relative abundance of the specific mRNAs in these preparations appeared to depend on the carbon source provided, with the preparations from CMC-grown cells having the greatest amount of cenB transcripts, followed by glycerol- and glucose-grown cells. Therefore, the transcription of this gene could be regulated by the carbon source provided to C. fimi. High-resolution nuclease S1 protection studies were used to map cenB mRNA 5' termini with a unique 5'-labeled DNA probe and C. fimi RNA isolated in vivo. With this procedure, three 5' termini were found in abundance upstream of the translational initiation ATG codon in RNA preparations from C. fimi grown on CMC, while less-abundant 5' termini were found 52 bases closer to the ATG codon in RNA prepared from C. fimi grown on any one of the three substrates. These results are indicative of a tandem promoter arrangement, with the ATG-proximal promoter directing constitutive low-level cenB transcription and the more distal promoter directing higher levels of transcription under the inducing effects of the cellulosic substrate. The corresponding transcripts were not detected in S1 mapping experiments with RNA isolated in vivo from Escherichia coli clones harboring recombinant plasmids carrying C. fimi genomic inserts. Comparative analysis of the 5' -flanking DNA sequences of the cenB gene and the cenA and cex genes of C. fimi (N. M. Greenberg, R. A. J. Warren, D. G. Kilburn, and R. C. Miller, Jr., J. Bacteriol. 169:646-653, 1987) revealed a region of 50 bases in which these sequences displayed at least 64% homology.

Uridine kinase, the rate-limiting enzyme in the activation (phosphorylation) of uridine and the corresponding chemotherapeutic analogues, is present as two isoenzymes localized exclusively in the cytosol of rapidly growing neoplasms, including the S-37 sarcoma, EL-4 leukaemia, HeLa cells (a human carcinoma) and the Novikoff hepatoma. The activities of the isolated isoenzymes are markedly decreased when the concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations approximating to those found in vivo. Further, comparisons of the Km values of isolated uridine kinases with those for cellular uptake of pyrimidine nucleosides and their rate of intracellular phosphorylation suggest that nucleoside-transport systems play a rate-limiting role in nucleoside analogue activation and consequently that it is impossible to estimate the Km of uridine kinase in the intact cell. During the development of tumour-cell resistance to 5-fluorouracil or 5-fluorouridine in vivo there was an early differential increase in the activity of a low-affinity (high-Km) uridine kinase isoenzyme, as measured in cell extracts, and a 7-fold increase in the Km values for the uptake of both uridine and 5-fluorouridine into the intact resistant cells.

Recent service developments in the NHS on the provision of talking therapies such as the Improving Access to Psychological Therapies (IAPT) initiative have made the compliance with clinical supervision (CS) inherent among its service guidelines. This paper presents the findings of an audit, measuring compliance with CS among clinicians providing psychological therapies within a military Department of Community Mental Health.

ABSTRACTBackground: Significant numbers of individuals leave the military and experience symptoms of posttraumatic stress disorder (PTSD). Veterans with PTSD symptoms rarely experience them in isolation, more commonly they are co-morbid with a range of other difficulties.Objective: Latent profile analysis (LPA) was used to explore the heterogeneity of PTSD symptom presentation. Following this, regression analysis was used to examine variables that predicted membership to the identified PTSD profiles.Methods: Data on childhood adversity, socio-demographic characteristics and mental health outcomes was collected from 386 male veterans who had engaged with mental health services in the UK.Results: LPA identified a six-profile model to best describe the sample. There was a Low symptom profile, a Severe symptom profileand four Moderatesymptom profiles. The Severe symptom profilewas the largest one, accounting for 37.57% of the sample. Five out of the six profiles had mean PTSD scores above the cut-off for probable PTSD. Higher rates of common mental health difficulties were associated with more symptomatic profiles.Discussion: As the vast majority of veterans met criteria for probable PTSD, the finding of six different profiles differing primarily quantitatively, but to some extent also qualitatively, suggests the importance of moving away from a ‘one-size fits all’ approach when it comes to treatments, towards developing interventions that are tailored to meet the specific PTSD and co-morbid symptoms profiles.