Identifying trajectories of change in sleep disturbance during psychological treatment for depression.

BACKGROUND: Sleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making. METHOD: This analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services. RESULTS: Six distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, unemployment status, antidepressant medication use, long-term health condition status, severity of depressive symptom, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well. LIMITATION: Single item on sleep disturbance used, no data on treatment adherence. CONCLUSIONS: These findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance.

Predicting post-treatment symptom severity for adults receiving psychological therapy in routine care for generalised anxiety disorder: a machine learning approach.

Approximately half of generalised anxiety disorder (GAD) patients do not recover from first-line treatments, and no validated prediction models exist to inform individuals or clinicians of potential treatment benefits. This study aimed to develop and validate an accurate and explainable prediction model of post-treatment GAD symptom severity. Data from adults receiving treatment for GAD in eight Improving Access to Psychological Therapies (IAPT) services (n=15,859) were separated into training, validation and holdout datasets. Thirteen machine learning algorithms were compared using 10-fold cross-validation, against two simple clinically relevant comparison models. The best-performing model was tested on the holdout dataset and model-specific explainability measures identified the most important predictors. A Bayesian Additive Regression Trees model out-performed all comparison models (MSE=16.54 [95 % CI=15.58; 17.51]; MAE=3.19; R²=0.33, including a single predictor linear regression model: MSE=20.70 [95 % CI=19.58; 21.82]; MAE=3.94; R²=0.14). The five most important predictors were: PHQ-9 anhedonia, GAD-7 annoyance/irritability, restlessness and fear items, then the referral-assessment waiting time. The best-performing model accurately predicted post-treatment GAD symptom severity using only pre-treatment data, outperforming comparison models that approximated clinical judgement and remaining within the GAD-7 error of measurement and minimal clinically important differences. This model could inform treatment decision-making and provide desired information to clinicians and patients receiving treatment for GAD.

Measurement invariance and differential item functioning of the PHQ-9 and GAD-7 between working age and older adults seeking treatment for common mental disorders.

BACKGROUND: The nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalised Anxiety Disorder (GAD-7) scale are widely used clinically and within research, and so it is important to determine how the measures, and individual items within the measures, are answered by adults of differing ages. This study sought to evaluate measurement invariance and differential item functioning (DIF) of the PHQ-9 and GAD-7 between working age and older adults seeking routine psychological treatment. METHODS: Data of working age (18-64 years old) and older (≥65) adults in eight Improving Access to Psychological Therapies (IAPT) services were used. Confirmatory factor analysis (CFA) was used to establish unidimensionality of the PHQ-9 and GAD-7, with multiple-group CFA to test measurement invariance and The Multiple Indicators, Multiple Causes Models approach to assess DIF. The employed methods were applied to a propensity score matched (PSM) sample in sensitivity analyses to control for potential confounding. RESULTS: Data from 166,816 patients (159,325 working age, 7491 older) were used to show measurement invariance for the PHQ-9 and GAD-7, with limited evidence of DIF and similar results found with a PSM sample (n = 5868). LIMITATIONS: The localised sample creates an inability to detect geographical variance, and the potential effect of unmeasured confounders cannot be ruled out. CONCLUSIONS: The findings support the use of the PHQ-9 and GAD-7 measures for working age and older adults, both clinically and in research settings. This study validates using the measures for these age groups to assess clinically significant symptom thresholds, and monitor treatment outcomes between them.

Examining bi-directional change in sleep and depression symptoms in individuals receiving routine psychological treatment.

BACKGROUND: Sleep disturbance is a common symptom of depression. There is conflicting evidence whether improvements in sleep might impact depressive symptoms, or whether treating the core depressive symptoms might improve sleep disturbance. This study explored the bi-directional impact of sleep and depressive symptom change among individuals receiving psychological treatment. METHODS: Session-by-session change in sleep disturbance and depressive symptom severity scores were explored in patients receiving psychological therapy for depression from Improving Access to Psychological Therapies services in England. Bi-directional change in sleep disturbance and depressive symptoms was modelled using random-intercept cross-lagged panel models with items from the PHQ-9. RESULTS: The sample included 17,732 adults that had received three or more treatment sessions. Both depressive symptoms and sleep disturbance scores decreased. Between initial timepoints, higher sleep disturbance was associated with lower depression scores, but after this point positive cross-lagged effects were observed for both the impact of sleep disturbance on later depressive symptoms, and depressive symptoms on later sleep disturbance scores. The magnitude of effects suggested depressive symptoms may have more impact on sleep than the reverse, and this effect was larger in sensitivity analyses. CONCLUSIONS: Findings provide evidence that psychological therapy for depression results in improvements in core depressive symptoms and sleep disturbance. There was some evidence that depressive symptoms may have more impact on sleep disturbance scores at the next therapy session, than sleep disturbance does on later depressive symptoms. Targeting the core symptoms of depression initially may optimise outcomes, but further research is needed to elucidate these relationships.

Transdiagnostic symptom dynamics during psychotherapy.

Psychotherapy is an effective treatment for many common mental health problems, but the mechanisms of action and processes of change are unclear, perhaps driven by the focus on a single diagnosis which does not reflect the heterogeneous symptom experiences of many patients. The objective of this study was to better understand therapeutic change, by illustrating how symptoms evolve and interact during psychotherapy. Data from 113,608 patients from psychological therapy services who completed depression and anxiety symptom measures across three to six therapy sessions were analysed. A panel graphical vector-autoregression model was estimated in a model development sample (N = 68,165) and generalizability was tested in a confirmatory model, fitted to a separate (hold-out) sample of patients (N = 45,443). The model displayed an excellent fit and replicated in the confirmatory holdout sample. First, we found that nearly all symptoms were statistically related to each other (i.e. dense connectivity), indicating that no one symptom or association drives change. Second, the structure of symptom interrelations which emerged did not change across sessions. These findings provide a dynamic view of the process of symptom change during psychotherapy and give rise to several causal hypotheses relating to structure, mechanism, and process.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

Adapting IAPT services to support frontline NHS staff during the Covid-19 pandemic: the Homerton Covid Psychological Support (HCPS) pathway.

The Coronavirus (Covid-19) pandemic is exerting unprecedented pressure on NHS Health and Social Care provisions, with frontline staff, such as those of critical care units, encountering vast practical and emotional challenges on a daily basis. Although staff are being supported through organisational provisions, facilitated by those in leadership roles, the emergence of mental health difficulties or the exacerbation of existing ones amongst these members of staff is a cause for concern. Acknowledging this, academics and healthcare professionals alike are calling for psychological support for frontline staff, which not only addresses distress during the initial phases of the outbreak but also over the months, if not years, that follow. Fortunately, mental health services and psychology professional bodies across the United Kingdom have issued guidance to meet these needs. An attempt has been made to translate these sets of guidance into clinical provisions via the recently established Homerton Covid Psychological Support (HCPS) pathway delivered by Talk Changes (Hackney & City IAPT). This article describes the phased, stepped-care and evidence-based approach that has been adopted by the service to support local frontline NHS staff. We wish to share our service design and pathway of care with other Improving Access to Psychological Therapies (IAPT) services who may also seek to support hospital frontline staff within their associated NHS Trusts and in doing so, lay the foundations of a coordinated response. KEY LEARNING AIMS: (1)To understand the ways staff can be psychologically and emotionally impacted by working on the frontline of disease outbreaks.(2)To understand the ways in which IAPT services have previously supported populations exposed to crises.(3)To learn ways of delivering psychological support and interventions during a pandemic context based on existing guidance and research.

An adapted mindfulness intervention for people with dementia in care homes: feasibility pilot study.

OBJECTIVE: Depression and anxiety are common in dementia. There is a need to develop effective psychosocial interventions. This study sought to develop a group-based adapted mindfulness programme for people with mild to moderate dementia in care homes and to determine its feasibility and potential benefits. METHODS: A manual for a 10-session intervention was developed. Participants were randomly allocated to the intervention plus treatment as usual (n = 20) or treatment as usual (n = 11). Measures of mood, anxiety, quality of life, cognitive function, stress and mindfulness were administered at baseline and 1 week post-intervention. RESULTS: There was a significant improvement in quality of life in the intervention group compared to controls (p = 0.05). There were no significant changes in other outcomes. CONCLUSIONS: The intervention was feasible in terms of recruitment, retention, attrition and acceptability and was associated with significant positive changes in quality of life. A fully powered randomised controlled trial is required. Copyright © 2017 John Wiley & Sons, Ltd.

Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370.

BACKGROUND AND PURPOSE: The KCNQ-encoded voltage-gated potassium channel family (Kv 7.1-Kv 7.5) are established regulators of smooth muscle contractility, where Kv 7.4 and Kv 7.5 predominate. Various Kv 7.2-7.5 channel enhancers have been developed that have been shown to cause a vasorelaxation in both rodent and human blood vessels. Recently, two novel Kv 7 channel enhancers have been identified, ML213 and NS15370, that show increased potency, particularly on Kv 7.4 channels. The aim of this study was to characterize the effects of these novel enhancers in different rat blood vessels and compare them with Kv 7 enhancers (S-1, BMS204352, retigabine) described previously. We also sought to determine the binding sites of the new Kv 7 enhancers. KEY RESULTS: Both ML213 and NS15370 relaxed segments of rat thoracic aorta, renal artery and mesenteric artery in a concentration-dependent manner. In the mesenteric artery ML213 and NS15370 displayed EC50 s that were far lower than other Kv 7 enhancers tested. Current-clamp experiments revealed that both novel enhancers, at low concentrations, caused significant hyperpolarization in mesenteric artery smooth muscle cells. In addition, we determined that the stimulatory effect of these enhancers relied on a tryptophan residue located in the S5 domain, which is the same binding site for the other Kv 7 enhancers tested in this study. CONCLUSIONS AND IMPLICATIONS: This study has identified and characterized ML213 and NS15370 as potent vasorelaxants in different blood vessels, thereby highlighting these new compounds as potential therapeutics for various smooth muscle disorders.

In silico investigation of a KCNQ1 mutation associated with familial atrial fibrillation.

Mutations in transmembrane domains of the KCNQ1 subunit of the I(Ks) potassium channel have been associated with familial atrial fibrillation. We have investigated mechanisms by which the S1 domain S140G KCNQ1 mutation influences atrial arrhythmia risk and, additionally, whether it can affect ventricular electrophysiology. In perforated-patch recordings, S140G-KCNQ1+KCNE1 exhibited leftward-shifted activation, slowed deactivation and marked residual current. In human atrial action potential (AP) simulations, AP duration and refractoriness were shortened and rate-dependence flattened. Simulated I(Ks) but not I(Kr) block offset AP shortening produced by the mutation. In atrial tissue simulations, temporal vulnerability to re-entry was little affected by the S140G mutation. Spatial vulnerability was markedly increased, leading to more stable and stationary spiral wave re-entry in 2D stimulations, which was offset by I(Ks) block, and to scroll waves in 3D simulations. These changes account for vulnerability to AF with this mutation. Ventricular AP clamp experiments indicate a propensity for increased ventricular I(Ks) with the S140G KCNQ1 mutation and ventricular AP simulations showed model-dependent ventricular AP abbreviation.

Characterization of Brucella abortus infection of bovine monocyte-derived dendritic cells.

Brucella abortus is a Gram negative facultative intracellular pathogen of cattle, and an important zoonosis in humans worldwide. Previous studies have shown that dendritic cells (DC) from humans and mice are highly permissive for Brucella survival and proliferation. Impairment of DC activation and maturation by Brucella infection has also been reported in these two species. The aim of this study was to characterize infection of bovine DC with B. abortus. Monocyte-derived DC (mdDC) were cultured from bovine peripheral blood mononuclear cells (PBMC) using the recombinant bovine cytokines IL-4 and GM-CSF. The resulting mdDC were DEC205(+), MHC class II(hi). Approximately 70% of the cultured cells were DEC205(+), MHC II(+). MdDC were infected with B. abortus strain 2308 at an MOI of 1 and 100. Parallel infection experiments were performed in monocyte derived macrophages (mdM) isolated from the same subjects. Bacteria were successfully killed by mdDC by 24 hours post infection (PI) with high and low dose of B. abortus, bacteria persisted in mdM infected with a high dose. Expression of IL-1b, IL-6, IL-10, IL-12p40, IFNγ, iNOS and TNFα in B. abortus infected and LPS stimulated mdDC at 6 and 24 hours PI were evaluated using RT-qPCR. At 6 hours PI all transcripts were increased over control cells and significantly less IL-10, IL-12p40, and IFNγ were expressed in mdDC infected with B. abortus compared to LPS stimulation. Evaluation of mdDC cultures by flow cytometry was performed. Flow cytometric analysis of infected and LPS stimulated mdDC 24 hours PI showed expression of CD80 and CD86 was impaired in two of the three animals analyzed. MHC class II expression was equivocal between the groups. From these results we conclude that cultured bovine mdDC are not permissive for intracellular proliferation of B. abortus, and infected mdDC exhibit some signs of maturational and activational impairment.

Immunophysiological responses of horses to a 12-hour rest during 24 hours of road transport.

Thirty-eight mature horses were assigned to one of two equal groups to evaluate two treatments consisting of either 24 hours of continuous road transport (24T) or two 12-hour periods of transport separated by off-loading, resting and feeding the horses for 12 hours (12/12T). A subset of six horses from each group served as controls for the other group. The horses were loaded into a commercial straight-deck trailer and travelled loose in one of two standard-sized compartments. After the journeys the horses were put back into their paddocks for a 24-hour recovery period. Venous blood samples were collected before loading, after unloading and after the 24-hour recovery period. Transport significantly increased the horses' cortisol concentrations, neutrophil counts and neutrophil:lymphocyte (nl) ratios, and decreased the numbers of all the lymphocyte subpopulation cell types. Collectively, no significant differences were observed between the two treatments in the horses' cortisol concentrations, total leucocyte counts, neutrophil and lymphocyte counts, nl ratios, and the cd8a+ and cd21+ lymphocyte subpopulations, but there were differences in the numbers of cd3+, cd4+, and cd8b+ subpopulations. The inclusion of a 12-hour rest-stop interrupted the transport-related decline in the lymphocyte subpopulations and allowed them to recover towards their resting levels.

Immunological responses and viral modulatory effects of vaccination with recombinant modified vaccinia virus Ankara (rMVA) expressing structural and regulatory transgenes of simian immunodeficiency virus (SIVmac32H/J5M).

BACKGROUND: The immunogenicity and protective efficacy of recombinant modified vaccinia virus Ankara (rMVA) vectors expressing structural (gag/pol, env) and regulatory (tat, rev, nef) genes of SIVmac251/32H-J5 (rMVA-J5) were assessed. METHODS: Immunization with rMVA constructs (2.5 x 10(7) IU) 32, 20 and 8 weeks pre-challenge was compared with 32 and 20 weeks but with a final boost 8 weeks pre-challenge with 2 x 10(6) fixed-inactivated HSC-F4 cells infected with SIVmac32H. Controls received rMVA vectors expressing an irrelevant transgene or were naïve challenge controls. All received 10 MID(50) SIVmac32H/J5 intravenously. RESULTS: Vaccinates immunized with rMVA-J5 exhibited significant, albeit transient, control of peak primary viraemia despite inconsistent and variable immune responses elicted by vaccination. Humoral and cellular responses to Env were most consistent, with lower responses to Nef, Rev and Tat. Increasing titres of anti-vaccinia neutralizing antibodies reflected the number and dose of rMVA inoculations. CONCLUSIONS: Improved combinations of viral vectors are required to elicit appropriate immune responses to control viral replication.

Photostabilization of organic UV-absorbing and anti-oxidant cosmetic components in formulations containing micronized manganese-doped titanium oxide.

Micronized titanium oxide (TiO(2)) and manganese-doped titanium oxide (TiO(2):Mn) particles have been incorporated into a variety of oil-in-water (O/W) and water-in-oil-in-water (W/O/W) emulsions in conjunction with the UV-absorbing organic compounds butyl methoxydibenzoylmethane (BMDM) and octyl methoxycinnamate (OMC) and with the anti-oxidants vitamin E and vitamin C. The retention of the organics under solar exposure has been shown to be significantly enhanced by the addition of TiO(2):Mn to the formulation. In the case of BMDM and OMC, the retention is increased from 20% and 24% to 63% and 83%, respectively, after two hours of solar exposure. In this system, TiO(2) particles are shown to provide only limited protection relative to BMDM and OMC. Vitamin E and vitamin C are actively degraded by the presence of TiO(2) in the emulsion during solar exposure. This effect is reversed with TiO(2):Mn, the use of which can protect >90% of anti-oxidants in both the oil and water phases of the formulation. The absence of reactive oxygen species (ROS) generation and surface scavenging of ROS by TiO(2):Mn is responsible for a significantly reduced ROS load on the organic components and consequent photostabilization of the emulsion.

Otarine Herpesvirus-1, not papillomavirus, is associated with endemic tumours in California sea lions (Zalophus californianus).

The purpose of this study was to determine if Otarine Herpesvirus-1 (OtHV-1) is associated with the presence of urogenital carcinomas in California sea lions. Polymerase chain reaction (PCR) analysis with primers specific for OtHV-1 was used to compare the prevalence of OtHV-1 infection in 15 sea lions affected by urogenital carcinoma with that of age-matched and juvenile tumour-free animals, and animals with tumours of non-urogenital origin. The herpesvirus was more prevalent (100%) and more widespread in the 15 animals with urogenital carcinoma than in 25 control animals, and was most often found in the urogenital tissue (vagina and prostate) and in the draining lymph nodes. Moreover, OtHV-1 DNA was not found in any juvenile animal, or in the neoplastic tissues of animals with non-urogenital tumours. Papillomavirus-specific PCR analysis of urogenital carcinoma tissues detected papillomavirus sequences in only one carcinomatous tissue. Further studies are needed to determine if OtHV-1 contributes to oncogenesis in the California sea lion; these data show, however, that OtHV-1 is associated with urogenital carcinomas, is preferentially present in urogenital tissues, and may be sexually transmitted. Papillomaviruses, which are known to contribute to urogenital tumours in other species, did not appear to be associated with the sea lion carcinomas.

Expressed MHC class II genes in sea otters (Enhydra lutris) from geographically disparate populations.

The major histocompatibility complex (MHC) is central to maintaining the immunologic vigor of individuals and populations. Classical MHC class II genes were targeted for partial sequencing in sea otters (Enhydra lutris) from populations in California, Washington, and Alaska. Sequences derived from sea otter peripheral blood leukocyte mRNAs were similar to those classified as DQA, DQB, DRA, and DRB in other species. Comparisons of the derived amino acid compositions supported the classification of these as functional molecules from at least one DQA, DQB, and DRA locus and at least two DRB loci. While limited in scope, phylogenetic analysis of the DRB peptide-binding region suggested the possible existence of distinct clades demarcated by geographic region. These preliminary findings support the need for additional MHC gene sequencing and expansion to a comprehensive study targeting additional otters.

Histochemical and immunohistochemical evidence of a bacterium associated with lesions of epizootic bovine abortion.

Epizootic bovine abortion (EBA), a tick-transmitted disease of pregnant cattle grazing foothill pastures, is a major cause of reproductive failure in California and adjacent states. Affected fetuses develop a chronic disease, resulting in late-term abortion or premature calving. Despite investigations spanning 50 years, to the authors' knowledge, the etiologic agent of EBA has not yet been isolated from affected fetuses or the tick vector. The diagnosis of EBA is based on gross and microscopic lesions. Recently, documentation that the etiologic agent is susceptible to antibiotics and identification of a unique 16S deltaproteobacterial rDNA gene sequence in 90% of thymus tissues from aborted fetuses have supported the role of a bacterial infection as the cause of EBA. To determine whether bacteria could be detected in the tissues, histochemical staining and immunohistochemical procedures were used on formalin-fixed, paraffin-embedded tissues. Use of a modified Steiner silver stain revealed small numbers of intracytoplasmic bacterial rods in 37 of 42 thymic samples from EBA-affected fetuses. Improved detection was achieved by use of immunohistochemical staining with serum from EBA-affected fetuses that resulted in detection of numerous bacterial rods in the cytoplasm of histiocytic cells in the thymus from all 42 EBA-affected fetuses. Immunohistochemical examination of additional tissues from 21 field and experimental EBA cases revealed positively stained intracytoplasmic bacterial rods in many organs with inflammatory lesions. Use of the modified Steiner stain and immunohistochemical staining of tissues from negative-control fetuses failed to reveal organisms. To the authors' knowledge, this is the first report to document morphologic evidence of a bacterium associated with the lesions of EBA.

MHC gene configuration variation in geographically disparate populations of California sea lions (Zalophus californianus).

Major histocompatibility complex (MHC) class II DRB genotypes were examined in two geographically isolated populations of California sea lions (Zalophus californianus) (Gulf of California and California coastal Pacific Ocean). Genomic DNA from 227 California sea lions was examined using eight sequence-specific primer (SSP) pairs flanking the putative peptide-binding site. A total of 40 different Zaca-DRB genotype configurations were identified among the 227 individuals. Using SSP-PCR, significant differences were found between coastal California and Gulf of California Zalophus populations in numbers of DRB sequences per individual and configuration of sequences within individuals. Additionally, unique local patterns of MHC diversity were identified among the Midriff Island animals. These population differences are consistent with either ecologically distinct patterns of selection pressures and/or geographical isolation. The consequences of these partitioned MHC configurations at the population level are as yet unknown; however, the worldwide increase in emerging marine diseases lends urgency to their examination.

Tissue distribution of phocine herpesvirus-1 (PhHV-1) in infected harbour seals (Phoca vitulina) from the central Californian coast and a comparison of diagnostic methods.

The polymerase chain reaction (PCR) was used to determine the tissue distribution of phocine herpesvirus-1 (PhHV-1) DNA in 20 stranded Pacific harbour seals (17 pups and three seals older than one year) that died during rehabilitation. The aim was to begin to define stages of infection and to investigate the relation between the presence of PhHV-1 in tissues, histological lesions and serology. PhHV-1 DNA was detected in a wide range of tissues from 10/17 pups and 3/3 subadults or adults. Different clinical patterns emerged from the examination of ante- and post-mortem samples. These patterns probably represented pups with active PhHV-1 infection, pups recovering from infection, and older harbour seals with chronic, reactivated infection. As PhHV-1 DNA was detected in tissues in the absence of typical histological lesions in seven seals and in the absence of PhHV-1 specific antibodies in four seals, it is clear that both histological examination and serology underestimate the presence of infection. These results showed that infection can occur in the absence of obvious disease and that seroconversion may be associated with clinical recovery.