Genome skimming elucidates the evolutionary history of Octopoda.

Phylogenies for Octopoda have, until now, been based on morphological characters or a few genes. Here we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes of twenty Octopoda specimens, comprising 18 species of Cirrata and Incirrata, representing 13 genera and all five putative families of Cirrata (Cirroctopodidae, Cirroteuthidae, Grimpoteuthidae, Opisthoteuthidae and Stauroteuthidae) and six families of Incirrata (Amphitretidae, Argonautidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, and Megaleledonidae) which were assembled using genome skimming. Phylogenetic trees were built using Maximum Likelihood and Bayesian Inference with several alignment matrices. All mitochondrial genomes had the 'typical' genome composition and gene order previously reported for octopodiforms, except Bathypolypus ergasticus, which appears to lack ND5, two tRNA genes that flank ND5 and two other tRNA genes. Argonautoidea was revealed as sister to Octopodidae by the mitochondrial protein-coding gene dataset, however, it was recovered as sister to all other incirrate octopods with strong support in an analysis using nuclear rRNA genes. Within Cirrata, our study supports two existing classifications suggesting neither is likely in conflict with the true evolutionary history of the suborder. Genome skimming is useful in the analysis of phylogenetic relationships within Octopoda; inclusion of both mitochondrial and nuclear data may be key.

Transcriptomic profiling of feline teeth highlights the role of matrix metalloproteinase 9 (MMP9) in tooth resorption.

Tooth resorption (TR) in domestic cats is a common and painful disease characterised by the loss of mineralised tissues from the tooth. Due to its progressive nature and unclear aetiology the only treatment currently available is to extract affected teeth. To gain insight into TR pathogenesis, we characterised the transcriptomic changes involved in feline TR by sequencing RNA extracted from 14 teeth (7 with and 7 without signs of resorption) collected from 11 cats. A paired comparison of teeth from the same cat with and without signs of resorption identified 1,732 differentially expressed genes, many of which were characteristic of osteoclast activity and differentiation, in particular matrix metalloproteinase 9 (MMP9). MMP9 expression was confirmed by qPCR and immunocytochemistry of odontoclasts located in TR lesions. A hydroxamate-based MMP9 inhibitor reduced both osteoclast formation and resorption activity while siRNA targeting MMP9 also inhibited osteoclast differentiation although had little effect on resorption activity. Overall, these results suggest that increased MMP9 expression is involved in the progress of TR pathogenesis and that MMP9 may be a potential therapeutic target in feline TR.

Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity.

Environmental enrichment (EE) is widely used to study the effects of external factors on brain development, function and health in rodent models, but very little is known of the effects of EE on the brain in a large animal model such as the pig. Twenty-four young pigs (aged 5 weeks at start of study, 1:1 male: female ratio) were housed in environmentally enriched (EE) pens and provided with additional enrichment stimulation (a bag filled with straw) once daily. Litter, weight and sex matched controls n= (24) were housed in barren (B) conditions. Behaviour was recorded on alternate days from study day 10. After 21 days, RNA-sequencing of the frontal cortex of male piglets culled one hour after the enrichment stimulation, but not those at 4 h after stimulation, showed upregulation of genes involved in neuronal activity and synaptic plasticity in the EE compared to the B condition. This result is mirrored in the behavioural response to the stimulation which showed a peak in activity around the 1 h time-point. By contrast, EE piglets displayed a signature consistent with a relative decrease in microglial activity compared to those in the B condition. These results confirm those from rodents, suggesting that EE may also confer neuronal health benefits in large mammal models, through a potential relative reduction in neuroinflammatory process and increase in neuroprotection driven by an enrichment-induced increase in behavioural activity.

Bathyal feasting: post-spawning squid as a source of carbon for deep-sea benthic communities.

In many oceanic carbon budgets there is a discrepancy between the energetic requirements of deep-sea benthic communities and the supply of organic matter. This suggests that there are unidentified and unmeasured food sources reaching the seafloor. During 11 deep-sea remotely operated vehicle (ROV) surveys in the Gulf of California, the remains (squid carcasses and hatched-out egg sheets) of 64 post-brooding squid were encountered. As many as 36 remains were encountered during a single dive. To our knowledge this is one of the largest numbers of natural food falls of medium-size deep-sea nekton described to date. Various deep-sea scavengers (Ophiuroidea, Holothuroidea, Decapoda, Asteroidea, Enteropneusta) were associated with the remains. Although many of the 80 examined ROV dives did not encounter dead squids or egg sheets (n = 69), and the phenomenon may be geographically and temporally restricted, our results show that dead, sinking squid transport carbon from the water column to the seafloor in the Gulf of California. Based on food fall observations from individual dives, we estimate that annual squid carcass depositions may regionally contribute from 0.05 to 12.07 mg C m-2 d-1 to the seafloor in the areas where we observed the remains. The sinking of squid carcasses may constitute a significant but underestimated carbon vector between the water column and the seafloor worldwide, because squid populations are enormous and are regionally expanding as a result of climate change and pressure on fish stocks. In the future, standardized methods and surveys in geographical regions that have large squid populations will be important for investigating the overall contribution of squid falls to regional carbon budgets.

The genomic architecture of mastitis resistance in dairy sheep.

BACKGROUND: Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed. All animals were genotyped with a custom-made 960-single nucleotide polymorphism (SNP) DNA array based on markers located in quantitative trait loci (QTL) regions for mastitis resistance previously detected in three other distinct dairy sheep populations. RESULTS: Heritable variation and strong positive genetic correlations were estimated for clinical mastitis occurrence and the three mastitis indicator traits. SNP markers significantly associated with these mastitis traits were confirmed on chromosomes 2, 3, 5, 16 and 19. We identified pathways, molecular interaction networks and functional gene clusters for mastitis resistance. Candidate genes within the detected regions were identified based upon analysis of an ovine transcriptional atlas and transcriptome data derived from milk somatic cells. Relevant candidate genes implicated in innate immunity included SOCS2, CTLA4, C6, C7, C9, PTGER4, DAB2, CARD6, OSMR, PLXNC1, IDH1, ICOS, FYB, and LYFR. CONCLUSIONS: The results confirmed the presence of animal genetic variability in mastitis resistance and identified genomic regions associated with specific mastitis traits in the Chios sheep. The conserved genetic architecture of mastitis resistance between distinct dairy sheep breeds suggests that across-breed selection programmes would be feasible.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Practice and documentation of palliative sedation: a quality improvement initiative.

BACKGROUND: Palliative sedation (ps), the continuous use of sedating doses of medication to intentionally reduce consciousness and relieve refractory symptoms at end of life, is ethically acceptable if administered according to standards of best practice. Procedural guidelines outlining the appropriate use of ps and the need for rigorous documentation have been developed. As a quality improvement strategy, we audited the practice and documentation of ps on our palliative care unit (pcu). METHODS: A pharmacy database search of admissions in 2008 identified, for a subsequent chart review, patients who had received either a continuous infusion of midazolam (≥10 mg/24 h), regular parenteral dosing of methotrimeprazine (≥75 mg daily), or regular phenobarbital. Documentation of the decision-making process, consent, and medication use was collected using a data extraction form based on current international ps standards. RESULTS: Interpretation and comparison of data were difficult because of an apparent lack of a consistent operational definition of ps. Patient records had no specific documentation in relation to ps initiation, to clearly identified refractory symptoms, and to informed consent in 60 (64.5%), 43 (46.2%), and 38 (40.9%) charts respectively. Variation in the medications used was marked: 54 patients (58%) were started on a single agent and 39 (42%), on multiple agents. The 40 patients (43%) started on midazolam alone received a mean daily dose of 21.4 mg (standard deviation: 24.6 mg). CONCLUSIONS: The lack of documentation and standardized practice of ps on our pcu has resulted in a quality improvement program to address those gaps. They also highlight the importance of conducting research and developing clinical guidelines in this area.

Public-private partnerships in neglected tropical disease control: the role of nongovernmental organisations.

Successful public-private partnerships for health control have usually included nongovernmental development organisations (NGDOs), and these have long been in the forefront of pinpointing particular social and health issues. The immensely successful control and elimination programmes for onchocerciasis are a case in point. NGDOs were the driving force in early advocacy for onchocerciasis control in West Africa, leading eventually to the remarkably effective and long lasting partnership of the Onchocerciasis Control Programme (OCP). With the donation of Mectizan(®), NGDOs were the driving force in developing onchocerciasis control in non-OCP countries, especially programmes for community based action. These were, further modified by the African Programme for Onchocerciasis Control (APOC) to become the successful Community Directed Interventions. NGDOs came together to coordinate activities in partnership with the World Health Organisation (WHO). Innovations by NGDOs led to integration of mass drug administration for Vitamin A deficiency and then for other parasitic diseases, leading to the current trend of preventive chemotherapy. The success of the NGDO Group for Onchocerciasis Control has led to the creation of similar groups for trachoma control and lymphatic filariasis elimination. These groups have now come together to form an NGDO Network for Neglected Tropical Disease control.

Ecophysiology of riparian cottonwood and willow before, during, and after two years of soil water removal.

Riparian cottonwood/willow forest assemblages are highly valued in the southwestern United States for their wildlife habitat, biodiversity, and watershed protection. Yet these forests are under considerable threat from climate change impacts on water resources and land-use activities to support human enterprise. Stream diversions, groundwater pumping, and extended drought have resulted in the decline of cottonwood/willow forests along many riparian corridors in the Southwest and, in many cases, the replacement of these forests with less desirable invasive shrubs and trees. Nevertheless, ecophysiological responses of cottonwood and willow, along with associated ecohydrological feedbacks of soil water depletion, are not well understood. Ecophysiological processes of mature Fremont cottonwood and coyote willow stands were examined over four consecutive growing seasons (2004-2007) near Salt Lake City, Utah, USA. The tree stands occurred near the inlet of a reservoir that was drained in the spring of 2005 and remained empty until mid-summer of 2006, effectively removing the primary water source for most of two growing seasons. Stem sap flux density (Js) in cottonwood was highly correlated with volumetric soil moisture (theta) in the upper 60 cm and decreased sevenfold as soil moisture dropped from 12% to 7% after the reservoir was drained. Conversely, Js in willow was marginally correlated with 0 and decreased by only 25% during the same period. Opposite patterns emerged during the following growing season: willow had a lower whole-plant conductance (kt) in June and higher leaf carbon isotope ratios (delta13C) than cottonwood in August, whereas k(t) and delta13C were otherwise similar between species. Water relations in both species recovered quickly from soil water depletion, with the exception that sapwood area to stem area (As:Ast) was significantly lower in both species after the 2007 growing season compared to 2004. Results suggest that cottonwood has a greater sensitivity to interannual reductions in water availability, while willow is more sensitive to longer periods of soil water depletion. These data shed light on the linkage between soil water deficits and ecophysiological processes of threatened riparian forests given potential land-use and long-term drought impacts on freshwater resources.

Clinical findings and recommendations made during home visits by a palliative care specialist physician.

Little has been reported regarding the nature of home visits by palliative care specialist physicians to assist in the management of complex cases. We determined the characteristics, actionable clinical findings and recommendations made during consecutive home visits conducted by a specialist physician for patients registered with a community palliative care service. Patient demographic information and clinical records were reviewed. Ninety-one patients received a total of 104 home and residential facility visits. Median patient age was 59 (Q1-Q3, 43-72). Ten children (under the age of 14) received a total of 15 visits. Seventy-three patients (80%) had a cancer diagnosis. Median visit duration was 60 min (Q1-Q3, 45-60). The major actionable clinical findings were pain (120), gastrointestinal (115), neuropsychiatric (58), mouth and skin (33) and respiratory (29). One-third of recommendations involved changes in analgesia regimen (opioids 67, adjuvants 44). The specialist physician home visit resulted in multiple patient care recommendations. This information may help palliative care programmes improve their care for patients and families in the community.

Is the KUB radiograph redundant for investigating acute ureteric colic in the non-contrast enhanced computed tomography era?

AIM: To establish whether non-contrast enhanced computed tomography (NCCT) renders the kidneys-ureters-bladder (KUB) radiograph redundant as the initial imaging investigation for suspected acute ureteric colic. MATERIALS AND METHODS: The imaging investigations for 120 patients consecutively admitted to an emergency department-led clinical decisions unit (CDU) with suspected acute ureteric colic were retrospectively reviewed. A multidisciplinary meeting reviewed the findings and recommended that KUB radiographs should not be routinely performed prior to NCCT. Prospective assessment of 116 consecutive patients admitted over a comparable period was then undertaken. RESULTS: In the retrospective group, 61 (50.8%) patients had calculi to account for symptoms (positive NCCT) and 59 (49.2%) patients did not have stone disease (negative NCCT). Ninety (75%) patients had a KUB radiograph prior to NCCT. However, in 46 (38% of total) of these patients the NCCT was negative for stones, and therefore, they had been subjected to an unnecessary radiographic examination. These results prompted a change in practice. In the subsequent and prospectively studied group, preliminary KUB radiographs were performed in only 6% of the patients, with no significant change in the positive NCCT rate (50.8 versus 51.7%) or the total number of examinations performed (120 versus 116). CONCLUSION: NCCT should be the initial imaging examination for acute ureteric colic. Up to 50% of patients with clinical suspicion do not have stone disease, and therefore, preliminary KUB radiographs with attendant radiation and cost implications are unjustified. Preliminary KUB radiographs can be omitted from the imaging pathway with no resultant indication creep or increase in demand for NCCT examinations.

Gender-specific patterns of aboveground allocation, canopy conductance and water use in a dominant riparian tree species: Acer negundo.

Acer negundo Sarg. (box elder) is a dioecious tree species that dominates riparian systems at mid elevations throughout the southwest and Intermountain West of the United States. Previous studies have shown that female A. negundo trees occur at higher frequencies along stream margins, whereas males occur at higher frequencies in drier microsites. To better understand the adaptive significance of sex ratio biases and their impact on the ecohydrology of riparian ecosystems, we examined whole-plant water relations and hydraulic properties of mature male and female A. negundo trees occurring within 1 m of a perennial stream channel. We hypothesized that (1) females would have significantly greater canopy water fluxes than males (particularly during periods of seed production: May-June), and (2) xylem in females is more hydraulically efficient but more vulnerable to cavitation than xylem in males. Mean sap flux density (J(s)) during the early growing season (May and June) was 43% higher in female trees than in male trees (n = 6 and 7 trees respectively, P < 0.0001). Mean J(s) in July and August remained 17% higher in females than in males (P = 0.0009). Mean canopy stomatal conductance per unit leaf area (g(s,leaf)) in May and June was on average 140% higher in females than in males (P < 0.0001). Mean g(s,leaf) in July and August remained 69% higher in female trees than in male trees (P < 0.0001). Canopy stomatal conductance scaled to basal area was 90 and 31% higher in females relative to males during May-June and July-August, respectively (P < 0.0001 during both periods). Conversely, there were no apparent differences in either branch hydraulic conductance or branch xylem cavitation vulnerability between genders. These results improve our capacity to describe the adaptive forces that shape the spatial distribution of male and female trees in dioecious species, and their consequences for ecohydrological processes in riparian ecosystems.

Transpiration and hydraulic strategies in a piñon-juniper woodland.

Anthropogenic climate change is likely to alter the patterns of moisture availability globally. The consequences of these changes on species distributions and ecosystem function are largely unknown, but possibly predictable based on key ecophysiological differences among currently coexisting species. In this study, we examined the environmental and biological controls on transpiration from a piñon-juniper (Pinus edulis-Juniperus osteosperma) woodland in southern Utah, USA. The potential for climate-change-associated shifts in moisture inputs could play a critical role in influencing the relative vulnerabilities of piñons and junipers to drought and affecting management decisions regarding the persistence of this dominant landscape type in the Intermountain West. We aimed to assess the sensitivity of this woodland to seasonal variations in moisture and to mechanistically explain the hydraulic strategies of P. edulis and J. osteosperma through the use of a hydraulic transport model. Transpiration from the woodland was highly sensitive to variations in seasonal moisture inputs. There were two distinct seasonal pulses of transpiration: a reliable spring pulse supplied by winter-derived precipitation, and a highly variable summer pulse supplied by monsoonal precipitation. Transpiration of P. edulis and J. osteosperma was well predicted by a mechanistic hydraulic transport model (R2 = 0.83 and 0.92, respectively). Our hydraulic model indicated that isohydric regulation of water potential in P. edulis minimized xylem cavitation during drought, which facilitated drought recovery (94% of pre-drought water uptake) but came at the cost of cessation of gas exchange for potentially extended periods. In contrast, the anisohydric J. osteosperma was able to maintain gas exchange at lower water potentials than P. edulis but experienced greater cavitation over the drought and showed a lesser degree of post-drought recovery (55% of pre-drought uptake). As a result, these species should be differentially affected by shifts in the frequency, duration, and intensity of drought. Our results highlight the sensitivity of this woodland type to potential climate-change-associated shifts in seasonal moisture patterns and demonstrate the utility of mechanistic hydraulic models in explaining differential responses of coexisting species to drought.

Effects of allopurinol on plasma uric acid levels in normouricaemic and hyperuricaemic green iguanas (Iguana iguana).

A two-phase cross-over therapeutic study was performed with 19 green iguanas (Iguana iguana) maintained within a preferred optimum temperature range of 26 to 37 degrees C. During phase 1, they were fed a normal vegetarian diet and medicated orally with either allopurinol or a placebo control once a day for seven days. Uric acid concentrations, total protein, packed-cell volumes (pcv) and bodyweights were recorded from each lizard before and after treatment to determine the effects of allopurinol. In phase 2, after a 10-day washout period, the iguanas were fed a high protein diet to induce hyperuricaemia. Normo- and hyperuricaemic iguanas that received 24.2 (3.2) mg/kg allopurinol had significantly lower mean (sd) uric acid concentrations (100.3 [53.1] micromol/l) than the controls (159.3 [100.3] micromol/l). There were no detectable interactions between the doses of allopurinol or placebo, and the iguanas' diet, weight, pcv or total protein. The allopurinol was well tolerated, and there was no significant clinical, gross or histological evidence of hepatic or renal toxicity in the iguanas that received the drug. However, in the kidneys of the hyperuricaemic iguanas that did not receive allopurinol there were proliferative changes in the glomeruli and degeneration of tubular epithelia. Allopurinol given orally at 25 mg/kg daily is able to reduce plasma uric acid levels by 41 to 45 per cent, and is therefore recommended for the treatment of hyperuricaemia in the green iguana.

Health care at the end of the road: opportunities from 20 years of partnership in onchocerciasis control.

The unprecedented decision of Merck & Co., Inc., to donate ivermectin through the Mectizan(R) Donation Program, has catalysed an exemplary partnership, to distribute the drug to the communities at risk of onchocerciasis, and empower them to take charge of the drug distribution themselves. Integration with other activities has always been part of the plan, but has been accelerated in recent years because of the need to strengthen primary health care, and to meet the challenges of integrating the rapid impact of Neglected Tropical Disease programmes. Activities that have been integrated include provision of vitamin A capsules, elimination of lymphatic filariasis, the distribution of insecticide-treated nets, and comprehensive eye health. Although these integrated activities show promising results for all programmes involved, challenges still remain. The risk of overburdening communities with multiple activities, and the problem of remuneration at the community level, are the major concerns, as is the need for effective coordination. The expanded onchocerciasis control partnership is a model of translating the eighth Millennium Development Goal (MDG), namely 'develop a global partnership for development', into action and also addresses other key MDGs. In 2006, the partnership provided more than 62 million treatments for onchocerciasis control, and offers a firm foundation from which to deliver other needed health interventions while safeguarding the achievements of onchocerciasis control thus far.

Evaluation of the need for endoscopy to identify low-risk patients presenting with an acute upper gastrointestinal bleed suitable for early discharge.

AIMS: To audit the safety of differing protocol-driven early-discharge policies, from two sites, for low-risk acute upper gastrointestinal (GI) bleeding and determine if default early (<24 h) in-patient endoscopy is necessary. METHODS: All patients with low-risk acute upper GI bleeding presenting to two separate hospital sites in Leeds from August 2002 to March 2005 were identified. Both hospitals operate nurse-led process-driven protocols for discharge within 24 h, but only one includes default endoscopy. Relevant information was obtained from patients' notes, patient administration systems, discharge letters and endoscopy records. RESULTS: 120 patients were admitted to site A and 74 to site B. Median length of stay on the clinical decisions unit was 12.6 h at site A and 9.4 h at site B (p = 0.045). Oesophagogastroduodenoscopy was performed on 89/120 (74%) patients at site A compared with only 7/74 (9%) at site B (p<0.001). Six of 120 (5%) patients from site A were admitted to hospital for further observation compared with 6/74 (8%) from site B (p = 0.38). Of the remaining patients, all were discharged within 24 h, and 8/114 (7%) at site A vs 17/68 (25%) at site B were given hospital clinic follow-up (p<0.001). None of the 194 patients had further bleeding or complications within 30 days. CONCLUSIONS: Patients admitted with a low-risk acute upper GI bleeding can be managed safely by a nurse-led process-driven protocol, based on readily available clinical and laboratory variables, with early discharge <24 h. Avoiding in-patient endoscopy appears to be safe but at the price of greater clinic follow-up.