Stabilizing selection and mitochondrial heteroplasmy in the Canada lynx (Lynx canadensis).

Mitochondrial DNA is commonly used in population genetic studies to investigate spatial structure, intraspecific variation, and phylogenetic relationships. The control region is the most rapidly evolving and largest non-coding region, but its analysis can be complicated by heteroplasmic signals of genome duplication in many mammals, including felids. Here, we describe the presence of heteroplasmy in the control region of Canada lynx (Lynx canadensis) through intra-individual sequence variation. Our results demonstrate multiple haplotypes of varying length in each lynx, resulting from different copy numbers of the repetitive sequence RS-2 and suggest possible heteroplasmic single nucleotide polymorphisms (SNPs) in both repetitive sequences RS-2 and RS-3. Intra-individual variation was only observed in the repetitive sequences while inter-individual variation was detected in the flanking regions outside of the repetitive sequences, indicating that heteroplasmic mutations are restricted to these repeat regions. Although each lynx displayed multiple haplotypes of varying length, we found the most common variant contained three complete copies of the RS-2 repeat unit, suggesting copy number is regulated by stabilizing selection. While genome duplication offers potential for increased diversity, heteroplasmy may lead to a selective advantage or detriment in the face of mitochondrial function and disease, which could have significant implications for wildlife populations experiencing decline (e.g., bottlenecks) as a result of habitat modification or climate change.

Considerations for the design of nutrition-sensitive production programmes in rural South Africa.

BACKGROUND: Very little has been researched about the efficacy, effectiveness, feasibility, sustainability and impact of food-based approaches on the diets and nutritional status of populations at risk of hunger and food insecurity. This study contributes knowledge about the impact of food-based approaches on the diets of populations at risk of hunger and food insecurity in four of the poorest rural communities in South Africa. The study investigated the consumption and production patterns of rural households (278 in summer and 280 in winter) in four sites in the poorest municipalities in South Africa. METHODS: A multistage stratified random sampling technique was applied to identify the communities and sample households for the quantitative survey and qualitative assessments. Qualitative and quantitative data were collected between 2013 and 2015 through focus group discussions (FGDs), key informant interviews and the two-round panel survey to cover both the summer and winter seasons at each site. RESULTS: Home gardening led to a significant positive increase in the consumption of white roots and tubers, dark green leafy vegetables, orange-coloured fruit and other fruit in the 24 h prior to the survey. Participation in a community garden led to significant increases in the consumption of dark green leafy vegetables and other vegetables. School gardening did not demonstrate any statistical relationships with the consumption of foods from the crop-related food groups. Crop production improved dietary diversity. Selling produce and irrigation showed a stronger improvement in dietary diversity. Seasonality affected the availability of fresh fruit and vegetables for home consumption in winter. CONCLUSIONS: Producing beyond that solely for home consumption has greater benefits for dietary diversity and a consumption-smoothing effect during the post-harvest period. Politicians and the scientific community should recognise the role that household and small-scale crop production plays in supporting household consumption and the provision of essential micronutrients despite constraints and disincentives. Production and education programmes should focus on strengthening existing good consumption patterns and promoting the consumption of foods that can improve dietary diversity.

Relationships between MRI fat distributions and sleep apnea and obesity hypoventilation syndrome in very obese patients.

PURPOSE: Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. METHODS: We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. RESULTS: Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p < 0.001). Gender was a significant confounder in these associations. No significant associations were found between MRI measures of adiposity and hypoventilation. CONCLUSIONS: In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.

Risk factors for dysphagia after a spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To determine the risk factors predictive of dysphagia after a spinal cord injury (SCI). SETTING: None. METHODS: A comprehensive literature search was performed in five scientific databases for English articles that identified risk factors for dysphagia after a SCI in adult (≥19 years) individuals. Data extracted included: author name, year and country of publication, participant demographics, sample size, study design, method of dysphagia diagnosis, and risk factor percentages. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. For identified risk factors, risk percentages were transformed into risk ratios (RR) with 95% confidence intervals. Quantitative synthesis was performed for risk factors reported in two or more studies using restricted maximum-likelihood estimator random effects models. RESULTS: Eleven studies met inclusion criteria of which ten studies were of moderate quality (n = 10). Significant risk factors included: age, injury severity, level of injury, presence of tracheostomy, coughing, voice quality, bronchoscopy need, pneumonia, mechanical ventilation, nasogastric tubes, comorbid injury, and a cervical surgery. Results of the quantitative synthesis indicated that the presence of a tracheostomy posed a threefold greater risk of the development of dysphagia (RR: 3.67); while, cervical surgery posed a 1.3 times greater risk of the development of dysphagia (RR: 1.30). CONCLUSIONS: Knowledge of these risk factors can be a resource for clinicians in the early diagnosis and appropriate medical management of dysphagia post SCI.

A meta-review of stress, coping and interventions in dementia and dementia caregiving.

BACKGROUND: There has been a substantial number of systematic reviews of stress, coping and interventions for people with dementia and their caregivers. This paper provides a meta-review of this literature 1988-2014. METHOD: A meta-review was carried out of systematic reviews of stress, coping and interventions for people with dementia and their caregivers, using SCOPUS, Google Scholar and CINAHL Plus databases and manual searches. RESULTS: The meta-review identified 45 systematic reviews, of which 15 were meta-analyses. Thirty one reviews addressed the effects of interventions and 14 addressed the results of correlational studies of factors associated with stress and coping. Of the 31 systematic reviews dealing with intervention studies, 22 focused on caregivers, 6 focused on people with dementia and 3 addressed both groups. Overall, benefits in terms of psychological measures of mental health and depression were generally found for the use of problem focused coping strategies and acceptance and social-emotional support coping strategies. Poor outcomes were associated with wishful thinking, denial, and avoidance coping strategies. The interventions addressed in the systematic reviews were extremely varied and encompassed Psychosocial, Psychoeducational, Technical, Therapy, Support Groups and Multicomponent interventions. Specific outcome measures used in the primary sources covered by the systematic reviews were also extremely varied but could be grouped into three dimensions, viz., a broad dimension of "Psychological Well-Being v. Psychological Morbidity" and two narrower dimensions of "Knowledge and Coping" and of "Institutionalisation Delay". CONCLUSIONS: This meta-review supports the conclusion that being a caregiver for people with dementia is associated with psychological stress and physical ill-health. Benefits in terms of mental health and depression were generally found for caregiver coping strategies involving problem focus, acceptance and social-emotional support. Negative outcomes for caregivers were associated with wishful thinking, denial and avoidance coping strategies. Psychosocial and Psychoeducational interventions were beneficial for caregivers and for people with dementia. Support groups, Multicomponent interventions and Joint Engagements by both caregivers and people with dementia were generally found to be beneficial. It was notable that virtually all reviews addressed very general coping strategies for stress broadly considered, rather than in terms of specific remedies for specific sources of stress. Investigation of specific stressors and remedies would seem to be a useful area for future research.

Effectiveness of transcranial direct current stimulation for the management of neuropathic pain after spinal cord injury: a meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to examine the effect of transcranial direct current stimulation (tDCS) on reducing neuropathic pain intensity in individuals with spinal cord injury (SCI). METHODS: Medline, CINAHL, EMBASE and PsycINFO databases were searched for all relevant articles published from 1980 to November 2014. Trials were included if (i) tDCS intervention group and a placebo control group were present; (ii) at least 50% of participants in the study had an SCI and there were at least three participants; (iii) participants were aged 18 years or older; and (iv) persistent pain for at least 3 months. Studies were excluded if: (i) the tDCS intervention group was compared with an active treatment group; (ii) there was insufficient reporting detail to enable pooling of data; and (iii) it was a nonclinical trial (that is, reviews, epidemiology, basic sciences). A standardized mean difference (SMD) ± s.e. and 95% confidence interval (CI) was calculated for each outcome of interest and the results were pooled using a fixed or random effects model, as appropriate. Effect sizes were interpreted as: small > 0.2, moderate > 0.5, large > 0.8. RESULTS: Five studies met inclusion criteria of which four were randomized controlled trials and one was a prospective controlled trial. The pooled analysis found a significant effect of tDCS on reducing neuropathic pain after SCI post treatment (SMD = 0.510 ± 0.202; 95% CI, 0.114-0.906; P < 0.012); however, this effect was not maintained at follow-up (SMD = 0.353 ± 0.272; 95% CI, -0.179 to 0.886; P < 0.194). A reduction of 1.33 units on a 10-item scale was observed post treatment. No significant adverse events were reported. CONCLUSION: Meta-analytic results indicate a moderate effect of tDCS in reducing neuropathic pain among individuals with SCI; however, the effect was not maintained at follow-up. A mean pooled decrease of 1.33 units on a 10-item scale was found post treatment. Several factors were implicated in the effectiveness of tDCS in reducing pain. Due to the limited number of studies and lack of follow-up, more evidence is required before treatment recommendations can be made.

Oral care post stroke: a scoping review.

Health concerns post stroke may be the result of, or exacerbated by, neglected oral health care (OHC). However, OHC may be challenging post stroke due to hemiparesis, hemiplegia, a lack of coordination, and/or cognitive deficits. The objective of this study was to conduct a scoping review and summarise the current state of knowledge pertaining to OHC post stroke. A literature search was conducted using the multiple databases (MEDLINE, CINAHL, EMBASE, etc.). Combinations of multiple keywords were searched: oral, dental, health, care, hygiene, teeth, dentures, tooth brushing, stroke, cardiovascular health and cardiovascular disease. A grey literature search was also conducted. Articles included were those published in English between 1970 and July 2013, which focused on at least one aspect of OHC among a stroke population. For clinical trials, ≥50% of the sample must have sustained a stroke. In total, 60 articles met inclusion and focused on three primary area: (i) OHC Importance/Stroke Implications; (ii) Current Research; and (iii) Current Practice. It was found that OHC concerns are mainly related to mastication, dysphagia/nutrition, hygiene, prostheses and quality of life. Research indicates that there is limited specialised and individual care provided, and there are few assessment tools, guidelines and established protocols for oral health that are specific to the stroke population. Further, dental professionals' and nurses' knowledge of OHC is generally inadequate; hence, proper education for health professionals in acute and rehabilitation settings, patients, and caregivers has been discussed.

Norovirus genotypes implicated in two oyster-related illness outbreaks in Ireland.

We investigated norovirus (NoV) concentrations and genotypes in oyster and faecal samples associated with two separate oyster-related outbreaks of gastroenteritis in Ireland. Quantitative analysis was performed using real-time quantitative reverse transcription polymerase chain reaction and phylogenetic analysis was conducted to establish the NoV genotypes present. For both outbreaks, the NoV concentration in oysters was >1000 genome copies/g digestive tissue and multiple genotypes were identified. In faecal samples, GII.13 was the only genotype detected for outbreak 1, whereas multiple genotypes were detected in outbreak 2 following the application of cloning procedures. While various genotypes were identified in oyster samples, not all were successful in causing infection in consumers. In outbreak 2 NoV GII.1 was identified in all four faecal samples analysed and NoV GII concentrations in faecal samples were >108 copies/g. This study demonstrates that a range of NoV genotypes can be present in highly contaminated oysters responsible for gastroenteritis outbreaks.

Community stroke rehabilitation teams: providing home-based stroke rehabilitation in Ontario, Canada.

BACKGROUND: Community stroke rehabilitation teams (CSRTs) provide a community-based, interdisciplinary approach to stroke rehabilitation. Our objective was to assess the effectiveness of these teams with respect to client outcomes. METHODS: Functional, psychosocial, and caregiver outcome data. were available at intake, discharge from the program, and six-month follow-up. Repeated measures analysis of covariance was performed to assess patient changes between time points for each outcome measure. RESULTS: A total of 794 clients met the inclusion criteria for analysis (54.4% male, mean age 68.5±13.0 years). Significant changes were found between intake and discharge on the Hospital Anxiety and Depression Scale total score (p=0.017), Hospital Anxiety and Depression Scale Anxiety subscale (p<0.001), Functional Independence Measure (p<0.001), Reintegration to Normal Living Index (p=0.01), Bakas Caregiver Outcomes Scale (p<0.001), and Caregiver Assistance and Confidence Scale assistance subscale (p=0.005). Significant gains were observed on the strength, communication, activities of daily living, social participation, memory, and physical domains of the Stroke Impact Scale (all p<0.001). These improvements were maintained at the 6-month follow-up. No significant improvements were observed upon discharge on the memory and thinking domain of the Stroke Impact Scale; however, there was a significant improvement between admission and follow-up (p=0.002). All significant improvements were maintained at the 6-month follow-up. CONCLUSIONS: Results indicate that the community stroke rehabilitation teams were effective at improving the functional and psychosocial recovery of patients after stroke. Importantly, these gains were maintained at 6 months postdischarge from the program. A home-based, stroke-specific multidisciplinary rehabilitation program should be considered when accessibility to outpatient services is limited.

Pneumonia in US hospitalized patients with influenza-like illness: BioSense, 2007-2010.

We used data from BioSense, a national electronic surveillance system, to describe pneumonia in hospitalized patients with influenza-like illness (ILI). Ninety-five hospitals from 20 states reported ICD-9-CM-coded inpatient final diagnosis data during the study period of September 2007 to February 2010. We compared the characteristics of persons with and without pneumonia among those with ILI-related hospitalizations. BioSense captured 26 987 ILI-related inpatient hospitalizations; 8979 (33%) had a diagnosis of pneumonia. Analysis of trends showed highest counts of pneumonia during the 2007-2008 season and the second 2009 pandemic wave. Pneumonia was more common with increasing age. Microbiology and pharmacy data were available for a subset of patients; 107 (5%) with pneumonia had a bloodstream infection and 17% of patients were prescribed antiviral treatment. Our findings demonstrate the potential utility of electronic healthcare data to track trends in ILI and pneumonia, identify risk factors for disease, identify bacteraemia in patients with pneumonia, and monitor antiviral use.

Bladder cancer in individuals with spinal cord injuries.

STUDY DESIGN: Prospective scoping review. OBJECTIVES: To conduct a scoping review of all the literature related to bladder cancer in individuals with spinal cord injuries (SCI). METHODS: Literature search of the databases Pubmed, CINAHL, ProQuest, PsychINFO and Scopus up to and including August 2012. Articles related to bladder cancer among SCI patients were identified, and data pertaining to epidemiology, risk factors, screening, prevention and management was reviewed and summarized. RESULTS: An association between bladder cancer and SCI was first reported in the 1960s, with some case reports suggesting an alarmingly high rate among SCI patients. More recent epidemiological studies have reported this risk to be substantially lower. However, bladder cancer in SCI patients tends to present at an earlier age and at a more advanced pathological stage than bladder cancer in the general population. Presenting symptoms may be atypical, and early recognition is important to improve prognosis with surgical resection. Several risk factors have been identified, including indwelling catheters, urinary tract infections and bladder calculi. Screening of SCI patients for bladder cancer is routinely recommended in many SCI management guidelines and by expert consensus; however, evidence for screening tools and protocols is lacking. CONCLUSION: Bladder cancer is a rare, and potentially lethal occurrence in SCI patients. Physicians need to have a high index of suspicion for bladder cancer, particularly among SCI patients managed with long-term indwelling catheters.

The impact of the COVID-19 pandemic on presentations of self-harm over an 18-month period to a tertiary hospital.

OBJECTIVES: To examine and compare rates and methods of self-harm presenting to a tertiary referral hospital during an 18-month period since the onset of the COVID-19 pandemic with a similar period immediately prior to the pandemic onset. METHODS: Data from an anonymized database compared rates of self-harm presentations and methods employed between 1st March 2020 and 31st August 2021 to a similar time-frame prior to the onset of the COVID-19 pandemic. RESULTS: A 9.1% increase in presentations with self-harm was noted since the onset of the COVID-19 pandemic. Periods of more stringent restrictions were associated with higher levels of self-harm (daily rate of 2.10 v 0.77). A higher lethality of attempt was demonstrated post-COVID-19 onset (χ2 = 15.38, p < 0.001). Fewer individuals presenting with self-harm were diagnosed with an adjustment disorder since the onset of the COVID-19 pandemic (n = 84, 11.1%, v. n = 112, 16.2%, χ2 = 7.898, p = 0.005), with no other differences pertaining to psychiatric diagnosis noted. More patients actively engaged with mental health services (MHS) presented with self-harm (n = 239 (31.7%) v. n = 137, (19.8%), χ2 = 40.798, p ≤ 0.001) since the onset of the COVID-19 pandemic. CONCLUSIONS: Despite an initial reduction, an increase in rates of self-harm has occurred since the onset of the COVID-19 pandemic with higher rates evident during periods of higher government mandated restrictions. An increase in active patients of MHS presenting with self-harm potentially relates to reduced availability of supports and particularly group activities. The recommencement of group therapeutic interventions for individuals attending MHS in particular is warranted.

Molecular phylogenetics and systematics of two enteric helminth parasites (Baylisascaris laevis and Diandrya vancouverensis) in the Vancouver Island marmot (Marmota vancouverensis).

Island biogeography can promote rapid diversification and speciation via geographic isolation and novel selection pressures. These same factors can threaten the persistence of island endemics by limiting gene flow and suitable habitat. Host-parasite interactions on islands introduce another dimension of complexity as both species must simultaneously adapt to exogenous and endogenous factors. One example of host-parasite island biogeography is the critically endangered Vancouver Island (VI) marmot (Marmota vancouverensis) which is endemic to VI, Canada, and hosts two enteric helminth parasites: Baylisascaris laevis, an ascarid nematode common in tribe Marmotini, and Diandrya vancouverensis, an anoplocephalid cestode endemic to the VI marmot. Here, we aligned novel sequences from B. laevis (six genes) and D. vancouverensis (two genes) with congeneric sequences from GenBank. Phylogenies reconstructed using Bayesian and maximum parsimony approaches consistently placed B. laevis in a morphoclade, and D. vancouverensis in a monophyletic clade sister to D. composita. Mean pairwise sequence divergence between D. vancouverensis and D. composita (9.06 ± 1.94%) surpassed commonly accepted thresholds for species delimitation, whereas divergence between VI and mainland populations of B. laevis (1.12 ± 0.78%) was comparable to (or sometimes greater than) pairwise divergence values between other Baylisascaris species. Disparity in the genetic divergence of each parasite may reflect differences in their life cycle, host specificity, virulence, and the chronological extent of their isolation. Detailed descriptions of the population genetic structure and effects of both parasites on their shared host are crucial next steps in understanding the history of B. laevis and D. vancouverensis on VI and informing conservation efforts for the VI marmot and its enteric helminth parasites.

The impact of service user's suicide on mental health professionals.

OBJECTIVES: Our principle objective was to examine the personal and professional impact of service user (SU) suicide on mental health professionals (MHPs). We also wished to explore putative demographic or clinical factors relating to SUs or MPHs that could influence the impact of SU suicide for MHPs and explore factors MHPs report as helpful in reducing distress following SU suicide. METHODS: A mixed-method questionnaire with quantitative and thematic analysis was utilised. RESULTS: Quantitative data indicated SU suicide was associated with personal and professional distress with sadness (79.5%), shock (74.5%) and surprise (68.7%) particularly evident with these phenomena lasting less than a year for more than 90% of MHPs. MHPs also reported guilt, reduced self-confidence and a fear of negative publicity. Thematic analysis indicated that some MHPs had greater expertise when addressing SU suicidal ideation and in supporting colleagues after experiencing a SU suicide. Only 17.7% of MHPs were offered formal support following SU suicide. CONCLUSION: SU suicide impacts MHPs personally and professionally in both a positive and negative fashion. A culture and clear pathway of formal support for MHPs to ascertain the most appropriate individualised support dependent on the distress they experience following SU suicide would be optimal.

Genomic gain and over expression of CCL2 correlate with vascular invasion in stage I non-seminomatous testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) are the most frequent solid tumour to affect young Caucasian adult males and have increased in incidence over recent decades. In clinical stage I non-seminomas, (NSGCT) histological vascular invasion (VI) is a prognostic factor for metastatic relapse. Using array comparative genomic hybridization, we have previously shown that the presence of VI is associated with gain of a region at 17q12, containing a cluster of genes encoding inflammatory cytokines. We here confirm this finding using fluorescence in situ hybridization (FISH) demonstrating gain in 12 out of 42 (29%) assessable samples. Interrogation of previously published expression microarray data suggests that of the genes contained within this region, CCL2 [monocyte chemoattractant protein 1 (MCP1)] is frequently overexpressed in TGCT. Immunohistochemistry confirms this finding in a collection of 67 clinical stage I NSGCT, demonstrating an association with the presence of VI (p=0.049) that was not seen with VEGF-A, MMP2 or MMP9, although all were frequently expressed. This work gives further insight into the mechanisms involved in invasion in this tumour type, which may ultimately have implications for the management of patients with stage I disease.

Sporadic duodenal polyps: classification, investigation, and management.

Sporadic duodenal polyps are uncommon, being found in up to 5% of patients referred for upper gastrointestinal endoscopy. They are often discovered incidentally and are usually asymptomatic. The histological subtype of polyps cannot always be determined on endoscopic appearance alone, and biopsy is advocated. The need for further imaging, endoscopic procedures, surgical resection, and surveillance is determined by the histological features, neoplastic potential and associated symptoms. This review describes the different subtypes of sporadic duodenal polyp: adenomas, hamartomas, gastric metaplasia, inflammatory fibroids, lipomas, leiomyomas, carcinoids, stromal tumors, solitary Peutz-Jeghers polyps, lymphomas, and other rare benign and malignant lesions. It describes the epidemiology, clinical presentation, investigation, management options, and screening and surveillance strategies for each, based on current evidence.

COVID-19 and its effect on emergency presentations to a tertiary hospital with self-harm in Ireland.

OBJECTIVES: This study aimed to assess the impact of COVID-19 on presentations to an acute hospital with self-harm. METHODS: All presentations to University Hospital Galway with self-harm were assessed during the peak period of the coronavirus crisis in Ireland, over the 3 months from 1 March to 31 May 2020. These data were compared with presentations in the same months in the 3 years preceding (2017-2019). Data were obtained from the anonymised service database. RESULTS: This study found that in 2020, the rate of presentation with self-harm dropped by 35% from March to April and rose by 104% from April to May, peaking from mid-May. When trends over a 4-year period were examined, there was a significantly higher lethality of attempt (p < 0.001), and significant differences in diagnosis (p = 0.031) in 2020 in comparison with the three previous years. The increased lethality of presentations remained significant after age and gender were controlled for (p = 0.036). There were also significant differences in the underlying psychiatric diagnoses (p = 0.018), notably with a significant increase in substance misuse disorders presenting during the 2020 study period. CONCLUSIONS: COVID-19 showed a reduction in self-harm presentations initially, followed by a sharp increase in May 2020. If a period of economic instability follows as predicted, it is likely that this will further impact the mental health of the population, along with rates of self-harm and suicidal behaviours. There is a need for research into the longer-term effect of COVID-19 and lockdown restrictions, especially with respect to self-harm.

Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents.

Interaction between the chemokine CXCL12 (SDF1) and the G-protein coupled receptor CXCR4 is responsible for the maintenance of adult stem cell niches and is known to play an important role in utero in the migration of primordial germ cells. We demonstrate expression of CXCL12 by Sertoli cells and confirm CXCR4 expression by the germ cell population of the adult human testes. CXCR4 is also known to mediate organ-specific patterns of metastases in a range of common cancers. We identify consistent expression of CXCR4 mRNA and protein in testicular germ cell tumours (TGCT) that accounts for their patterns of relapse in sites of known CXCL12 expression. Extragonadal primary germ cell tumours express CXCR4 and their sites of occurrence are coincident with areas of known CXCL12 expression in utero. We show that CXCL12 stimulates the invasive migration of a TGCT cell line in vitro in a CXCR4-dependent fashion and activates ERK. Furthermore, we demonstrate that expression of CXCL12 in stage I non-seminomas is significantly associated with organ-confined disease post-orchidectomy and reduced risk of relapse (p = 0.003). This may be through the loss of CXCL12 gradients that might otherwise attract cells away from the primary tumour. We propose CXCL12 expression as a potential predictor of subsequent relapse that could lead to avoiding unnecessary treatment and associated late toxicities. Our observations support a role for CXCL12/CXCR4 in the adult germ cell population and demonstrate pathological function in germ cell tumour development and metastasis that may have clinical utility.

Coccoliths as paleoclimatic indicators of pleistocene glaciation.

Selected species of Coccolithophoridae from recent sediments and mid-Wisconsin glacial sediments of the North Atlantic were examined in an attempt to determine cooling effects. All species showed a definite shift southward during the glacial period. The average shift in this planktonic population was 15 degrees of latitude, with the greatest change in the eastern Atlantic. A paleoisotherm map can be drawn on the basis of the temperature boundaries of coccolithophorids. The species boundaries indicate a possible shift in position of the subtropical gyral to a glacial position roughly parallel to the 33-degree line of latitude.

Precessional forcing of nutricline dynamics in the equatorial atlantic.

Climate control of nutricline depth in the equatorial Atlantic can be monitored by variations in the abundance of the phytoplankton species Florisphaera profunda. A conceptual model, based on in situ evidence, associates high abundances of F. profunda with a deep nutricline and low abundances with a shallow nutricline. A 200,000-year record of F. profunda relative abundances, obtained from a deep-sea core sited beneath the region of maximum equatorial divergence at 10 degrees W, has 52 percent of its variance centered on the 23,000-year precessional band. Cross-spectral analysis between the signals of F. profunda and sea-surface temperature, independently derived from zooplankton species, shows their 23,000-year cycles to be coherent and nearly in phase. Abundance minima of F. profunda coincide with times of December perihelion, whereas abundance maxima coincide with June perihelion. These relations indicate that nutricline dynamics in the divergence region of the equatorial Atlantic are controlled by variations in the tropical easterlies, forced by the precessional component of orbital insolation, on time scales greater than 10,000 years.