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Imported, minimally processed food products have been historically associated with several hepatitis A outbreaks in Australia. Here, we report the first known hepatitis A outbreak in Australia linked to consumption of imported fresh Medjool dates. Between June and September 2021, six genetically identical hepatitis A cases were notified in New South Wales and the Australian Capital Territory. All cases reported date consumption during their exposure period. The implicated dates were positive for hepatitis A virus (HAV) by reverse transcription polymerase chain reaction. Rapid detection of this outbreak and the swift implementation of control measures was facilitated by two key factors. Firstly, Australian international border closures implemented in response to the COVID-19 pandemic meant that a common locally-acquired, as opposed to travel-acquired, source for cases was strongly suspected. Secondly, prompt awareness of a hepatitis A outbreak in the United Kingdom (which was found to be associated with date consumption) allowed for early hypothesis generation and investigation. This paper details the epidemiological and microbiological factors involved in this outbreak investigation and the actions taken to mitigate public health risk.

Facilitating coexistence between people and wildlife is a major conservation challenge in East Africa. Some conservation models aim to balance the needs of people and wildlife, but the effectiveness of these models is rarely assessed. Using a case‐study approach, we assessed the ecological performance of a pastoral area in northern Tanzania (Manyara Ranch) and established a long‐term wildlife population monitoring program (carried out intermittently from 2003 to 2008 and regularly from 2011 to 2019) embedded in a distance sampling framework. By comparing density estimates of the road transect‐based long‐term monitoring to estimates derived from systematically distributed transects, we found that the bias associated with nonrandom placement of transects was nonsignificant. Overall, cattle and sheep and goat reached the greatest densities and several wildlife species occurred at densities similar (zebra, wildebeest, waterbuck, Kirk's dik‐dik) or possibly even greater (giraffe, eland, lesser kudu, Grant's gazelle, Thomson's gazelle) than in adjacent national parks in the same ecosystem. Generalized linear mixed models suggested that most wildlife species (8 out of 14) reached greatest densities during the dry season, that wildlife population densities either remained constant or increased over the 17‐year period, and that herbivorous livestock species remained constant, while domestic dog population decreased over time. Cross‐species correlations did not provide evidence for interference competition between grazing or mixed livestock species and wildlife species but indicate possible negative relationships between domestic dog and warthog populations. Overall, wildlife and livestock populations in Manyara Ranch appear to coexist over the 17‐year span. Most likely, this is facilitated by existing connectivity to adjacent protected areas, effective anti‐poaching efforts, spatio‐temporal grazing restrictions, favorable environmental conditions of the ranch, and spatial heterogeneity of surface water and habitats. This long‐term case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is restricted in space, time, and numbers., To provide evidence for livestock–wildlife coexistence, we present data on long‐term (intermittently from 2003 to 2008 and regularly from 2011 to 2019) monitoring and population dynamics of livestock and wildlife species in a managed pastoral area in northern Tanzania. Our results show constant livestock population trajectories and constant to increasing wildlife population trends. This case study illustrates the potential of rangelands to simultaneously support wildlife conservation and human livelihood goals if livestock grazing is managed sustainably.

The auditory frequency weighted daily sound exposure level (SEL) is used in many jurisdictions to assess possible injury to the hearing of marine life. Therefore, using daily SEL to describe soundscapes would provide baseline information about the environment using the same tools used to measure injury. Here, the daily SEL from 12 recordings with durations of 18-97days are analyzed to: (1) identify natural soundscapes versus environments affected by human activity, (2) demonstrate how SEL accumulates from different types of sources, (3) show the effects of recorder duty cycling on daily SEL, (4) make recommendations on collecting data for daily SEL analysis, and (5) discuss the use of the daily SEL as an indicator of cumulative effects. The autocorrelation of the one-minute sound exposure is used to help identify soundscapes not affected by human activity. Human sound sources reduce the autocorrelation and add low-frequency energy to the soundscapes. To measure the daily SEL for all marine mammal auditory frequency weighting groups, data should be sampled at 64kHz or higher, for at least 1min out of every 30min. The daily autocorrelation of the one-minute SEL provides a confidence interval for the daily SEL computed with duty-cycled data. (C) 2019 Acoustical Society of America.

Shorthorn sculpin (Myoxocephalus scorpius) are among the most numerous consumers in the Arctic nearshore marine habitats. Despite this, little is known about their movement ecology or predator–prey interactions, particularly with Arctic cod (Boreogadus saida), an important forage fish in the Arctic. Using acoustic telemetry, the movements of tagged sculpin and cod were quantified based on specific locations using a Vemco positioning system during open water when both species were present in the near shore. Movement trajectories of sculpin distinguish three unique types: foraging and feeding behaviour and large transiting movements. The relative time of each of these movement types were correlated to biotic (presence of large numbers of acoustically tagged Arctic cod) and abiotic factors (percent ice coverage and temperature). This study provides unique data on the movement, feeding ecology, and behaviour of an abundant Arctic benthic fish that demonstrates similar movement types to temperate fish. However, further study is needed to quantify specifically the trophic interactions of these important fish and impact on food webs in the rapidly changing Arctic.

The inland waters around southern Vancouver Island and northern Washington State, known as the Salish Sea, host critical habitat for endangered southern resident killer whales (SRKW). This is, however, a highly traversed area, with approaches to industrial ports and coastal cities, international shipping lanes, ferry routes, and considerable recreational vessel traffic. Vessel noise is a key threat to SRKW prosperity, and so conservation measures directed to mitigate its effects have been explored annually since 2017. Here, we describe trials undertaken in 2020, which included spatially limited slowdown zones, exclusion areas as Interim whale Sanctuary Zones (ISZs), and a lateral displacement of tug transits to increase the distance between their route and SRKW foraging areas. To assess each of the measures we first considered the level of mariner participation using data from the Automated Identification Systems (AIS), mandatory for commercial vessels. Knowing this, the changes in soundscape were examined, focused on impacts on broadband (10 Hz to 100 kHz) ambient noise and the frequencies used by SRKW for communication (500 Hz to 15 kHz) and echolocation (15 to 100 kHz). A control period of two-months prior to trial initiation was used to quantify the changes. High levels (> 80%) of compliance were found for each measure, except ISZs, where observance was low. Median reduction in speeds ranged from 0.2–3.5 knots. Resulting sound reductions were most notable in the lower frequencies, although reductions were also recorded in SRKW pertinent ranges. Tug displacement also reduced ambient noise in these frequencies, despite making up a small portion of the overall traffic. The management trials were effective in reducing potential impacts singularly and in concert. Greater awareness and stakeholder engagement may increase compliance and, therefore, the efficacy of measures in the future.

The promotion of ketone body (KB) metabolism via ketosis has been suggested as a strategy to increase exercise performance. However, studies in humans and animals have yielded inconsistent results. The purpose of the current study was to examine the effects of ketosis, achieved via fasting or a short-term ketogenic diet (KD), on endurance exercise performance in female mice. After 8 h of fasting, serum KB significantly increased and serum glucose significantly decreased in fasted compared to fed mice. When subjected to an endurance exercise capacity (EEC) test on a motorized treadmill, both fed and fasted mice showed similar EEC performance. A 5-week KD (90% calories from fat) significantly increased serum KB but did not increase EEC times compared to chow-fed mice. KD mice gained significantly more weight than chow-fed mice and had greater adipose tissue mass. Biochemical tissue analysis showed that KD led to significant increases in triglyceride content in the heart and liver and significant decreases in glycogen content in the muscle and liver. Furthermore, KD downregulated genes involved in glucose and KB oxidation and upregulated genes involved in lipid metabolism in the heart. These findings suggest that a short-term KD is not an effective strategy to enhance exercise performance and may lead to increased adiposity, abnormal endogenous tissue storage, and cardiometabolic remodeling.

Caitlin O’Neill explores how engaging black future texts is both significant and necessary to the survival of African descended people, and for the ability of black women and girls to thrive in the twenty-first century. In this chapter, O’Neill explores creative, affirmative answers to Mark Dery’s question: “Can a community whose past has been deliberately rubbed out, and whose energies have subsequently been consumed by the search for legible traces of its history, imagine possible futures?” O’Neill highlights the long history of work that black women have contributed to the black speculative fiction tradition. They also work to establish an Afrofuturistic feminist genealogy, investigating works from Octavia Butler to Janelle Monae while privileging the speculative fiction, fantasy, and other creative production of black women.

Introduction Myelofibrosis (MF) is one of the classic myeloproliferative neoplasms and can occur de novo or following transformation from polycythemia vera (PPV MF) or essential thrombocythemia (PET MF). It can be associated with constitutional symptoms and splenomegaly, both of which can negatively impact quality of life. The only curative option for MF is allogeneic stem cell transplantation. Studies have shown that JAK2 inhibitors such as ruxolitinib are effective in reducing both splenomegaly and symptom burden. Although there is no approved treatment for patients who progress on ruxolitinib, anecdotal evidence suggests patients may respond to a re-challenge of ruxolitinib after drug cessation. Patients and Methods We conducted a multi-institutional, retrospective case series to study patients who were re-challenged with ruxolitinib after inadequate response to or loss of response with an initial treatment course. Thirteen patients were identified. Six patients had primary MF, 3 patients had PPV MF, and 4 patients had PET MF. Ten patients were JAK2-positive, 2 were CALR-positive, and 1 patient had neither mutation. Nine patients received 1 ruxolitinib re-challenge, and 4 received 2 re-challenges. Response was defined as improvement in constitutional symptoms and/or reduction in spleen size. Results During the primary treatment course with ruxolitinib, there was improvement in constitutional symptoms and reduction in spleen size in 92% and 85% of patients, respectively. Following cessation of ruxolitinib, all patients received a first re-challenge course with improvement in symptoms and splenomegaly in 92% and 69%, respectively. Of the 4 patients who received a second re-challenge course of ruxolitinib, all had improvements in spleen size and constitutional symptoms. Six patients have continued on a first or second ruxolitinib re-challenge course with good response. Conclusion Our study demonstrates that re-exposure to ruxolitinib following a period of treatment cessation in patients with MF can lead to durable responses with regards to both splenomegaly and symptom burden.

Even though over half of the world's soil organic carbon (SOC) is stored in subsoils (> 20 cm deep), and the old ages of subsoil OC indicate its cycling differs from surface SOC, there are few studies examining in situ decomposition processes in deep soils. Here, we added 13C-labeled fine roots to 15, 55, and 95 cm depths of a well characterized coniferous forest Alfisol and monitored the amount of root-derived C remaining over 6, 12, and 30 months. We recovered the root-derived C in microbial phospholipid fatty acids (PLFAs) after 6 months and in coarse (> 2 mm) particulate, fine (< 2 mm) particulate, and dense, mineral-associated pools after 6, 12, and 30 months. Overall, root decomposition in the first 6 months was similar among all depths but significantly diverged at 30 months with faster decomposition at 15 cm than at 95 cm. There were more fungal and Gram negative-associated PLFAs at 15 cm than at 95 cm, and 13C analysis revealed those microbial groups preferred the added root carbon to native SOC. Mineral-associations were not the cause of slower decomposition at depth because similar amounts of applied root C was recovered in the dense fraction at all depths. The largest difference among depths was in the amount of root C recovered in the coarse particulate fraction, which was greater at 95 cm (50%) than at 15 cm (15%). Slower decomposition of the particulate pool at depth likely contributed to the increase in C:N ratios and depletion of δ13C values below 60 cm depth in our soil profiles. Simulations of these soils using the CORPSE model, which incorporates microbial priming effects and mineral stabilization of SOC, reproduced patterns of particulate and mineral-associated SOC over both time and depth and suggested that a lack of priming by root exudates at depth could account for the slower decomposition rate of particulate root material. Decomposition of deep particulate SOC may increase if root exudation or dissolved OC transport to depth increases.

Passive acoustic recorders were deployed over two years (February 2018–March 2020) in the Salish Sea to monitor the underwater soundscape. Seasonal cycles and differences between the open Strait of Juan de Fuca and protected inner waterways were pervasive during this period. A comparison between natural and human-derived noise demonstrated the impact of anthropogenic activities on the sound field. Elevated ambient noise levels during winter resulted predominantly from greater sea states and storm events. Abiotic additions were defined through correlations to wind speed, wave and precipitation measures. Vessel noise was a pervasive anthropogenic addition; commercial vessel noise was consistently present, whereas smaller vessels showed weekly and diurnal patterns, especially during the summer when their presence increased. A better understanding of the different soundscape constituents, and when each dominates, is crucial to understanding the human impact on underwater ecosystems and the organisms within them, leading to more effective mitigation measures.

Background: Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm that results in bone marrow failure and frequently leads to acute myeloid leukemia (AML). Hypomethylating agents (HMA) are the only FDA-approved treatment for MDS and among few options for chemotherapy-ineligible patients with AML. There are limited options for patients in whom HMA therapy fails and who are not candidates for allogeneic stem cell transplant, so therapies that complement or restore sensitivity to HMAs are needed. Studies have shown increases in bone marrow microvessel density (MVD) and angiogenic markers in patients with MDS and AML. A decrease in MVD has been shown to correlate with response to hypomethylating agents in MDS. A receptor-ligand interaction, comprised of receptor EphB4 and membrane localized ligand EphrinB2, mediates angiogenesis in normal tissue and appears to be a target unique to many cancer types. We have previously shown EphB4 to be highly expressed and a driver of leukemic cell survival in a subset of AML patients. Our group has developed a human fusion protein, sEphB4-HSA, that blocks bidirectional signaling induced by EphB4-EphrinB2 interaction to inhibit tumor cell proliferation and angiogenesis. In phase I clinical trials of sEphB4-HSA in various tumor types, there were no myelosuppressive effects and minimal toxicity. Given its safety in phase I and potential to inhibit leukemic cell proliferation and angiogenesis, we proposed a pilot trial to evaluate the safety of sEphB4-HSA in combination with HMAs in MDS and AML patients who have failed treatment with HMAs. Methods: This pilot study was designed to enroll 6 patients with relapsed/refractory intermediate or high-risk MDS and 6 patients with AML refractory to or relapsed to HMA treatment and who are deemed unfit for chemotherapy. Treatment consisted of sEphB4-HSA 15 mg/kg IV every 2 weeks in combination with the FDA-approved HMA most recently or currently being used for treatment (decitabine 20mg/m2 IV/1hr on days 1 to 5 every 28 days or azacitidine 75mg/m2 SC or IV on days 1 to 7 every 28 days). Patients were treated for as long as they were receiving clinical benefit up to 12 months. The primary endpoint was toxicity and tolerability of sEphB4-HSA in combination with HMA. Toxicity was assessed and graded after each cycle according to the CTCAE version 4. Tolerability was defined as the ability to complete two cycles of treatment without the occurrence of dose-limiting toxicity. A secondary efficacy endpoint was to assess best overall response, based on the IWG Working Group Criteria for MDS and AML, during the first two cycles of treatment. Enrollment was stopped after 7 patients due to expiration of funding. Results: Three patients with intermediate-risk MDS were treated for a median duration of 6 cycles (2-12) and 4 patients with AML were treated for 2 cycles. Median age was 75.5 years (67.9-84.8) and 57.1% were male. HMA included azacitadine in 6 patients and decitabine in one patient. There were no dose-limiting toxicities. There were 8 grade 3/4 events attributed to HMA, which included: neutropenia (2), thrombocytopenia (3), and leukopenia (3). There were 3 grade 3/4 events attributed to sEphB4, which included: febrile neutropenia (1), leukopenia (1), and hypertension (1). Of the MDS patients, 2 had stable disease, 1 patient after 2 cycles and 1 patient after 4 cycles. One patient achieved a hematologic improvement-erythroid after 6 cycles. AML patients had no disease response. Reasons for treatment discontinuation were death (1), disease progression (2), patient's decision (1), physician's decision (2), and hospice (1). Notably, a comparison of bone marrow biopsies at baseline and after 8 weeks of treatment demonstrated a decrease in MVD (Figure 1). Discussion: This pilot study found sEphB4 in combination with HMAs to be tolerable with no significant toxicity beyond that expected with HMA therapy and associated with potential clinical benefit in MDS patients. Improvement in abnormal bone marrow MVD may indicate a potential for sEphB4-HSA plus HMA therapy to alter the malignant microenvironment in MDS/AML. Disclosures No relevant conflicts of interest to declare.

Background: Novel coronavirus infection (SARS CoV-2 or COVID-19) is associated with a high risk of thrombotic complications, including macro- and micro-thrombi in major organs, leading to increased morbidity and mortality. Anticoagulant use, mainly heparin, which has both anticoagulant and anti-inflammatory properties, has been suggested as potentially beneficial. However, the optimal dose of anticoagulant for patients with COVID-19 is unknown. Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19. Methods: This single-center retrospective cohort study is part of an ongoing Quality Improvement project on the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option, being conducted at our medical center. Data on the type, dose, and indication for anticoagulation as well as outcomes including thrombosis, bleeding and survival was collected for inpatients diagnosed with COVID-19 between mid-March and June 15, 2020. To address COVID-coagulopathy we developed a d-dimer-based anticoagulation protocol for patients with COVID-19 (Figure 1). We recorded anticoagulant use as either standard prophylactic, escalated prophylactic (low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units or enoxaparin 0.5mg/kg subcutaneously every 12 hours) or standard therapeutic dose used during the hospitalization. The primary endpoints assessed were ISTH-defined major and clinically relevant non-major bleeding (CRNMB) events and survival. Secondary endpoints included incidence of breakthrough thrombosis and duration of hospitalization. Results: A total of 263 patients with COVID-19 were reviewed. Of these, 68.44% of patients received prophylactic, 12.55% escalated prophylactic and 19.01% therapeutic dosage. Of total, 129 (49%) were receiving ICU level of care. No major bleeding events were observed. The incidence of CRNMB was 4.56% in the whole cohort, which did not differ significantly between the escalated prophylactic and therapeutic groups (12% and 12.12%, respectively). Patients treated with standard prophylaxis had less CRNMB (1.11%), but this was not statistically significant in a multivariate analysis that included other confounding factors such as age, sex, ethnicity, BMI, comorbidity, HASBLED bleeding risk, and sepsis induced coagulopathy score (SICS). The mortality rate was 12.6% in the whole cohort (7.22%, 21.21% and 26% in prophylactic, escalated prophylactic, and therapeutic dosage, respectively). Factors significantly associated with increased mortality included age and ICU level of care (HR 1.10, 95%CI [1.05, 1.15] and HR 20.42, 95%CI [2.84, 146.72], respectively). The use of therapeutic dose heparin and high-flow nasal cannula demonstrate a survival benefit in multivariate analysis (HR 0.13, 95%CI [0.04,0.44] and HR 0.23, 95%CI [0.07, 0.72], respectively; Figure 2). Breakthrough thrombosis occurred in 7 (2.66%) patients; 1 (0.56%), 1 (3.03%) and 5 (10%)) in prophylactic, escalated prophylactic and therapeutic dosage, respectively but very few diagnostic tests were performed during this time period. Duration of hospitalization was significantly longer in the therapeutic dose group when compared to escalated prophylaxis and standard prophylactic groups. Conclusion: In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH prophylaxis. By multivariate analysis, implementation of a d-dimer-titrated anticoagulation strategy was not associated with increased CRNMB. Therapeutic dose heparin based on a d-dimer-driven anticoagulation protocol was associated with a survival benefit in COVID19-infected patients. Limitations of this study include the retrospective observational nature and a lack of a uniform diagnostic protocol for patients with suspected VTE. Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population. Disclosures No relevant conflicts of interest to declare.

Objective Cerebral oximetry is a non-invasive system that uses near infrared spectroscopy to measure regional cerebral oxygenation (rSO2) in the frontal lobe of the brain. Post-cardiac arrest rSO2 may be associated with survival and neurological outcomes in out-of-hospital cardiac arrest patients; however, no studies have examined relationships between rSO2 and neurological outcomes following in-hospital cardiac arrest (IHCA). We tested the hypothesis that rSO2 following IHCA is associated with survival and favorable neurological outcomes. Design Prospective study from nine acute care hospital in the United States and United Kingdom. Patients Convenience sample of IHCA patients admitted to the intensive care unit with post-cardiac arrest syndrome. Interventions Cerebral oximetry monitoring (Equanox 7600, Nonin Medical, MN, USA) during the first 48 h after IHCA. Measurements and Main Results Subject’s rSO2 was calculated as the mean of collected data at different time intervals: hourly between 1−6 h, 6−12 h, 12−18 h, 18−24 h and 24−48 h. Demographic data pertaining to possible confounding variables for rSO2 and primary outcome were collected. The primary outcome was survival with favorable neurological outcomes (cerebral performance scale [CPC] 1−2) vs severe neurological injury or death (CPC 3−5) at hospital discharge. Univariate and multivariate statistical analyses were performed to correlate cerebral oximetry values and other variables with the primary outcome. Among 87 studied patients, 26 (29.9%) achieved CPC 1−2. A significant difference in mean rSO2 was observed during hours 1−2 after IHCA in CPC 1−2 vs CPC 3−5 (73.08 vs. 66.59, p = 0.031) but not at other time intervals. There were no differences in age, Charlson comorbidity index, APACHE II scores, CPR duration, mean arterial pressure, PaO2, PaCO2, and hemoglobin levels between two groups. Conclusions There may be a significant physiological difference in rSO2 in the first two hours after ROSC in IHCA patients who achieve favorable neurological outcomes, however, this difference may not be clinically significant.

Soil profiles are rarely homogeneous. Resource availability and microbial abundances typically decrease with soil depth, but microbes found in deeper horizons are still important components of terrestrial ecosystems. By studying 20 soil profiles across the United States, we documented consistent changes in soil bacterial and archaeal communities with depth. Deeper soils harbored communities distinct from those of the more commonly studied surface horizons. Most notably, we found that the candidate phylum Dormibacteraeota (formerly AD3) was often dominant in subsurface soils, and we used genomes from uncultivated members of this group to identify why these taxa are able to thrive in such resource-limited environments. Simply digging deeper into soil can reveal a surprising number of novel microbes with unique adaptations to oligotrophic subsurface conditions., While most bacterial and archaeal taxa living in surface soils remain undescribed, this problem is exacerbated in deeper soils, owing to the unique oligotrophic conditions found in the subsurface. Additionally, previous studies of soil microbiomes have focused almost exclusively on surface soils, even though the microbes living in deeper soils also play critical roles in a wide range of biogeochemical processes. We examined soils collected from 20 distinct profiles across the United States to characterize the bacterial and archaeal communities that live in subsurface soils and to determine whether there are consistent changes in soil microbial communities with depth across a wide range of soil and environmental conditions. We found that bacterial and archaeal diversity generally decreased with depth, as did the degree of similarity of microbial communities to those found in surface horizons. We observed five phyla that consistently increased in relative abundance with depth across our soil profiles: Chloroflexi, Nitrospirae, Euryarchaeota, and candidate phyla GAL15 and Dormibacteraeota (formerly AD3). Leveraging the unusually high abundance of Dormibacteraeota at depth, we assembled genomes representative of this candidate phylum and identified traits that are likely to be beneficial in low-nutrient environments, including the synthesis and storage of carbohydrates, the potential to use carbon monoxide (CO) as a supplemental energy source, and the ability to form spores. Together these attributes likely allow members of the candidate phylum Dormibacteraeota to flourish in deeper soils and provide insight into the survival and growth strategies employed by the microbes that thrive in oligotrophic soil environments.

Anthropogenic noise associated with shipping has emerged as a major disruptor of aquatic animal behavior worldwide. The Arctic marine realm has historically experienced little noise‐generating human activity; however, the continual loss of sea ice has facilitated a dramatic increase in shipping activity. Here, we use a combination of acoustic telemetry and modeling of ship noise to examine the temporospatial habitat use of key Arctic forage fish, Arctic cod (Boreogadus saida) in the presence and absence of vessels in Resolute Bay, Nunavut, Canada. The presence and movement of vessels induced a horizontal shift in the home ranges of Arctic cod with low core overlap when compared to periods without vessel activity. Home range displacement occurred near the vessel. Individuals also altered their swimming behaviors in response to vessel presence with searching decreasing and travelling increasing in proportion. Results indicate that Arctic cod perceive vessel noise and presence as a threat and react by moving away and decreasing exploratory activities. These changes in fish behavior also coincide with the critical open water feeding period suggesting an interruption in exploitation of important and seasonally abundant food resources, and carry broader implications for dependent seabirds and marine mammals, and indirectly for all Arctic indigenous peoples’ subsistence and long‐term cultural traditions. Our study implies that strategic management is required for aquatic acoustic disturbance as an environmental stressor in the Arctic marine ecosystem, and highlights ecologically and socially important impacts that require timely conservation action.

Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2-63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy.

Background: Idiopathic erythrocytosis (IE) is an entity characterized by a persistently elevated hemoglobin, variable erythropoietin (EPO) level, absence of janus kinase 2 (JAK2) mutations suggestive of polycythemia vera (PV) and no identifiable secondary cause. Previous studies have compared IE to PV, showing a lower incidence of venous thrombosis and leukemic transformation in IE but similar incidence of arterial events. PV is known to be associated with constitutional symptoms and splenomegaly, while hereditary erythrocytosis can be associated with recurrent headaches and fatigue. A comprehensive assessment of clinical features including symptoms in IE has not been performed. Methods: Patients signed informed consent to participate in an observational study approved by the Institutional Review Board. Enrollment criteria included: age 18 years or older; hemoglobin level greater than 16 g/dL on two occasions at least 3 months apart or greater than 15 g/dL if undergoing phlebotomy; negative testing for JAK2 mutations; and negative work up for secondary causes of erythrocytosis. Baseline assessment included history and physical exam, vital signs, pulse oximetry, and body mass index. Baseline laboratory exams included a complete blood cell count, complete metabolic panel, C-reactive protein, iron panel, ferritin, hemoglobin A1C, erythropoietin level. Abdominal ultrasound was performed to evaluate for splenomegaly. The Myeloproliferative Symptom Assessment Form (MPN-SAF) was used to assess for the presence and severity of a broad range of symptoms that may be expected to occur in patients with IE. The MPN-SAF was administered at baseline and every 6 months thereafter. Results: 35 patients had data available for analysis. Patient characteristics are shown in Table 1. The most prevalent co-morbid conditions were those known to be associated with cardiovascular disease risk and metabolic syndrome, including hepatic steatosis identified on abdominal ultrasound in 63% of patients. Three (8.6%) patients had a history of venous or arterial thrombosis. Two (5.8%) patients had a history of lymphoma (NK/T-cell and Hodgkin). Three patients (8.6%) had a first-degree relative with a myeloproliferative neoplasm (chronic myelomonocytic leukemia, essential thrombocytosis and polycythemia vera) and one patient had a son with IE and history of stroke. 16 (46%) patients were taking aspirin and 11 (31%) had undergone phlebotomy within 3 months of study enrollment. Patients reported the following symptoms on the MPN-SAF at baseline: fatigue (77%), early satiety (57%), difficulty sleeping (57%), numbness/tingling (51%), headaches (49%), concentration problems (40%), itching (40%), bone pain (37%), night sweats (37%), depression (37%), abdominal pain (37%), abdominal discomfort (37%), inactivity (37%), problems with sexual desire/function (34%), dizziness/lightheadedness (31%), cough (26%), fever (17%), and unintentional weight loss (17%). Fatigue carried the highest average symptom intensity (3.77, SD 3.17). Discussion: In this study, we describe the clinical features associated with IE in a multiracial cohort. Patients with IE are frequently symptomatic and have a high incidence of hepatic steatosis by ultrasound. Disclosures No relevant conflicts of interest to declare.

Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex immunopathology and pathogenesis characterized by thrombocytopenia and bleeding manifestations. The disorder is separated into primary (idiopathic) ITP and secondary ITP, when associated with other immune or lymphoproliferative disorders and certain chronic infections. Helicobacter pylori (H. pylori) is a recognized bacterial cause of ITP. In regions with high prevalence of infection, bacterial eradication has resulted in improvement in platelet count. However, the prevalence of H. pylori infection and response to antimicrobial therapy in North American ITP patients is reportedly low. We evaluated the prevalence of H. pylori infection in ITP patients diagnosed and treated at a large urban medical center. Eighty-two patients were screened for H. pylori, by stool antigen (n = 54), H. pylori breath test (n = 11), and H. pylori antibodies (n = 16), of which 15 (18.3%) were white non-Hispanic (WNH), 55 (67%) Hispanic (H), 8 (9.8%) Asian (A), and 4 (4.9%) African-American (AA). Of the screened patients, 36/82 (43.9%) tested positive for H. pylori. The prevalence of H. pylori infection within the represented ethnic groups was 2/15 (13%) WNH, 29/55 (52.7%) H, 3/8 (37.5%) A, and 2/4 (50%) AA. There was a significant difference in prevalence of infection comparing WNH and H patients (p = 0.007). There were 36 treated patients, with H. pylori eradication documented in 26 patients. Fifteen of the 26 patients were evaluable for response with 8 of 15 (53%) having clinical responses, 6 complete responses, and 2 partial responses. Our study demonstrates an increased prevalence of H. pylori infection in the Hispanic ITP population with a reasonable platelet response among patients with H. pylori eradication.

Since ‘mixed’ was first offered as an option in the ethnicity question in the 2001 England and Wales Census, Britain's recognition of, and interest in, mixed (or ‘multiracial’) people and families has not abated. Recent studies have focused primarily upon how mixed people identify themselves, or how parents racially identify their multiracial children. But Britain now has a population of multiracial individuals who are themselves parents, about whom we know very little. What are the particular concerns for multiracial individuals who are parents? Do multiracial people (who are parents) want to steer their children toward a particular kind of upbringing, and if so, toward what (and why)? This paper is an in-depth exploration of the various ways in which different types of multiracial people in Britain raise their children. Our main finding is that a significant majority of multiracial parents engage in parenting practices that emphasize a cosmopolitan ethos.

This paper explores how multiracial parents with White partners articulate narratives of ethnic and racial ‘dilution’ and cultural loss in relation to the socialization of their children. In our broader study of how multiracial parents raise their children, we found that parents commonly spoke of concerns around dilution and generational change in relation to four key themes: the loss of cultural knowledge and diminishing practices that connected parents and their children to a minority ancestry; the embodiment of White-appearing children and the implications of this for family relationships; the use of biological or genetic discourses in relation to reduced blood quantum; and concerns amongst Black/White participants about whitening and the loss of racial consciousness. Parental understandings of dilution varied greatly; some expressed sadness at ‘inevitable’ loss; others were more philosophical about generational change; and others still proactively countered loss through strategies to connect their children to their minority heritages. We show that despite growing awareness of the social constructedness of race and an emergent cosmopolitanism among these parents, discourses of genetics, cultural lineage, and the ‘naturalness’ of race continue to hold sway amongst many multiracial parents.

With climate change resulting in unpredictable sea ice conditions between years, it is crucial to gain a more comprehensive understanding of the subsequent effects on Arctic marine ecosystems. Arctic cod (Boreogadus saida) play a key role in the Arctic marine food web, serving as a food source that is estimated to contribute up to 75 % of energy transfer to higher trophic levels. To investigate Arctic cod residency and distribution in Resolute Bay (74°44′N, 095°04′W), 85 individuals from four locations in the bay were captured, measured, weighed, implanted with acoustic tags and subsequently tracked on an acoustic array of 49 receivers. Two main periods of residence in the bay were identified, the first in open water and the second under ice cover, and both concluded with a collective mass departure of fish. A generalised linear mixed model was used to investigate the influence of variables on Arctic cod presence/absence in the bay, indicating that ingress and egress were influenced by environmental changes, particularly those associated with the transition from open-water to the ice-covered period. Timing and distribution, during the study period, appeared to be influenced by a combination of physiological acclimation, and a balance between resource availability and refuge from predators. Receiver site Residence Index (RI) analysis revealed strong site fidelity of fish towards the northern areas of the bay, and this behaviour was consistent between tagging groups and individuals, indicating that the majority of tagged cod were representative of a single school. This study represents the first employment of acoustic telemetry to monitor the movements of individual Arctic cod over 9 months, incorporating both open-water and ice-covered periods.

Introduction: Idiopathic erythrocytosis (IE) is characterized by a persistently elevated hemoglobin, equivocal erythropoietin (EPO) levels, absence of janus kinase 2 (JAK2) mutations suggestive of polycythemia vera (PV) and no secondary cause. One study used a targeted 21 gene next-generation sequencing panel and identified novel variants in known erythrocytosis-related genes as well as novel genes associated with the oxygen-sensing pathway. However, expanded sequencing of blood and matched tissue samples in a large ethnically diverse group of IE patients has not been performed. Methods: All patients signed informed consent to participate in an observational study approved by the Institutional Review Board; they provide blood and buccal mucosa samples at study entry and at 24-month follow-up. Patients were enrolled if JAK2 testing and a complete work up for secondary causes was negative. They were required to have hemoglobin levels greater than 16 g/dL on two occasions or greater than 15 g/dL if undergoing phlebotomy. Our initial sequencing of 20 IE patients was performed utilizing high resolution whole-exome sequencing of circulating blood samples (disease) at a mean coverage of 390x and matched normal (buccal) samples at mean coverage of 300x. To stratify samples by genetic ancestry, we performed a population stratification principle component analysis (PCA) and STRUCTURE using Ancestry Informative Markers derived from 1K Genome Phase1_v3 Exome database. The primary in-silico analysis was performed on the baseline samples from treatment-naïve patients. The whole-exome data was generated in accordance to GATK's best practices with same filters applied as described by Exome Aggregation Consortium. The additional downstream in-silico paired analysis was performed using MutSig2.0 (Mutation Significance) algorithm to determine significant mutations and GISTIC (The Genomic Identification of Significant Targets in Cancer) to identify the significant copy number events, IPA (Ingenuity Pathway Analysis) to determine pathways along with other computational . Results: Median age at baseline was 52 years (range 35-71). Six patients (30%) were female and 14 (70%) were male. Median values and ranges for laboratory parameters at baseline were as follows: WBC 6.6 x 109/L (5-9.7), Hgb 17 g/dL (15.5-19.8), Plt 218 x 109/L (86-374), and EPO level 9.8 IU/L (2-14.3). Three patients had a personal history of malignancy, including 2 with lymphoma. Two patients had a family history of myeloid malignancy (chronic myeloid leukemia and PV). Our ancestry analysis of initial 20 patients with IE identified 6 patients with high European percent ancestry (EUR), 1 patient with high Asian percent ancestry (EAS) and 13 patients with high percent Ad Mixed ancestry (AMR). In our cohort, 60% (12/20) of patients had been also diagnosed with a liver disorder (11 with fatty liver, 1 with cirrhosis) that was not significantly different across populations. We identified, on average, 42 non-silent somatic mutations (not present in the buccal samples) in whole blood across our cohort with no statistical difference (p=0.671) in mutation burden between ancestry groups or between patients with and without liver disease. Age, gender, and ethnicity were not associated with mutation burden. Utilizing MutSig algorithm, we identified a novel candidate gene, CHAF1A, with high mutation prevalence of 30% in patients with IE. Further analysis of mutation landscape identified somatic nonsilent mutations in 25 known oncogenes which were present in at least 10% of patients. Our mutation signatures in IE identified a significant association with failure of double stranded DNA repair. Only one patient had a mutation in TET2. Further analysis of copy number indicated copy number loss in genes such as SETD3 and GSH associated with chromatin assembly which may suggest alterations in chromatin assembly and changes in the epigenome. Our analysis also identified a high number of 9p and 13q gains in patients with IE. Conclusion: In this study, we utilized high-resolution next generation sequencing in association with comprehensive clinical annotation to determine potential molecular drivers of IE in a multi-ethnic population. We identified somatic mutations in a subset of patients which may represent clonal hematopoiesis. Long term follow up of outcomes in this cohort may clarify the significance of these mutations in the pathogenesis of IE. Disclosures No relevant conflicts of interest to declare.

The Salish Sea encompasses the waters between southern British Columbia mainland coast, Vancouver Island, and Washington State. Its waters are used by commercial and recreational fishers, host shipping traffic to the major ports of Vancouver and Seattle, and is travelled frequently by local ferries. It is also an important habitat for many marine mammal species, including the endangered Southern Resident Killer Whale (Orcinus orca). Southern Resident Killer Whales use calls, whistles, and clicks to communicate and find prey. Human activities on the water may affect the marine acoustic environment by masking whale vocalizations, which in turn will negatively impact the ability of the whales to forage and socialize. A field study was conducted to measure acoustic transmission loss at various places in the Salish Sea. Sound signals simulating killer whale call elements were broadcast from different angles to a calibrated hydrophone. Results from the study showed that acoustic transmission loss is highly spatially variable in this area. We suggest that these observations are due to changes in oceanography conditions and ambient sound levels, which are important factors to consider when assessing impact on Southern Resident Killer Whales. [Work supported by the Oceans Protection Plan of the Government of Canada.]

Whether some languages or dialects are spoken faster or slower than others constitutes a gap in the understanding of sociolinguistic variation. Speech tempo is interconnected with the social, physical and psychological marking of speech. This study examines regional variation in articulation rate and its manifestations across speaker age, gender, and speaking situations (reading vs. informal talk). The results of an experimental investigation show that articulation rate differs significantly between two regional varieties of American English examined here. A group of Northern speakers (from Wisconsin) spoke significantly faster than a group of Southern speakers (from North Carolina). With regard to age and gender, young adults read faster than older adults in both regions; in informal talks, however, only Northern young adults spoke faster than older adults. Effects of gender were smaller and less consistent; men generally spoke slightly faster than women did. As the body of work on the sociophonetics of American English continues to grow in scope and depth, we argue that it is important to include fundamental phonetic information as part of our catalog of regional differences and patterns of change in American English.

Objective: There is a need for practical, efficient and broad-reaching diabetes self-management interventions that can produce changes in lifestyle behaviours such as healthy eating and weight loss. The objective of this study was to evaluate such a computer-assisted intervention. Methods: Type 2 diabetes primary care patients ( n=335) from fee-for-service and health maintenance organization settings were randomized to social cognitive theory-based tailored self-management (TSM) or computer-aided enhanced usual care (UC). Intervention consisted of computer-assisted self-management assessment and feedback, tailored goal-setting, barrier identification, and problem-solving, followed by health counsellor interaction and follow-up calls. Outcomes were changes in dietary behaviours (fat and fruit/vegetable intake), haemoglobin A1c (HbA1c), lipids, weight, quality of life, and depression. Results: TSM patients reduced dietary fat intake and weight significantly more than UC patients at the 2-month follow-up. Among patients having elevated levels of HbA1c, lipids or depression at baseline, there were consistent directional trends favouring intervention, but these differences did not reach significance. The intervention proved feasible and was implemented successfully by a variety of staff. Conclusions: This relatively low-intensity intervention appealed to a large, generally representative sample of patients, was well implemented, and produced improvement in targeted behaviours. Implications of this practical clinical trial for dissemination are discussed.

BACKGROUND Health benefits associated with diets rich in vegetables and fruit (VF) are often attributed to the antioxidant activity of their constituent phytochemicals. However, in vivo evidence that VF actually reduce markers of oxidative stress is limited. OBJECTIVE An 8-wk dietary intervention was conducted to test the hypothesis that increased VF consumption decreases oxidative stress. Urinary excretion of 8-isoprostane F2alpha (8-iso-PGF2alpha) was used as an index of whole-body lipid peroxidation. DESIGN The diets evaluated had comparable amounts of all macronutrients but varied in their content of VF. After a 2-wk low-VF (3.0 servings/d) run-in diet, 246 women were randomly assigned to receive either 3.6 (low) or 9.2 (high) servings VF/d. The low-VF group was switched to the high-VF diet during the final 2 wk of the study. Blood and first-void urine specimens were obtained at baseline and at 2-wk intervals thereafter. RESULTS The run-in diet reduced 8-iso-PGF2alpha concentrations by 33% (P < 0.0001). The excretion of 8-iso-PGF2alpha with the low-VF diet remained the same as that with the run-in diet, whereas urinary concentrations of 8-iso-PGF2alpha were further reduced (P < 0.01) by the high-VF diet, either fed throughout the study or when the diet was switched from low to high VF (P = 0.05). The greatest reductions in 8-iso-PGF2alpha were observed in subjects in the highest quartile of baseline concentrations of 8-iso-PGF2alpha. CONCLUSIONS A significant reduction in the excretion of 8-iso-PGF2alpha was induced by the run-in diet and the high-VF diet. The degree of reduction was related to the subject's baseline urinary concentration of 8-iso-PGF2alpha.

The patient-centered medical home (PCMH) is a practice model that is intended to improve the quality of care by making it safer, more comprehensive, integrated, and personal. However, most family medicine residency programs are not fully prepared to train residents on this idealized model. The Colorado Family Medicine Residency PCMH Project's overall objective is to transform 10 residency practices into PCMHs through practice improvement and curriculum redesign. This paper focuses on the programs' implementation of key PCMH components into the residency curricula and the impact on resident self-perceived competence in and use of PCMH components.Mixed-method evaluation assessed PCMH curricular characteristics, routine use of PCMH components in patient care, and perceived resident competence after implementation of quality improvement coaching and PCMH curriculum tools. Baseline and follow-up PCMH semi-structured curriculum interviews assessed elements included in the residency programs' curricula. The PCMH Clinician Assessment (PCMH-CA) Survey assessed routine use of PCMH components in patient care. The PCMH Competency Self-Assessment Survey assessed residents' perceived competency in applying PCMH elements in patient care.Qualitative data results demonstrated active efforts by the residency programs to implement key PCMH components. Survey results showed significant improvement from baseline to follow-up (12--36 months).Implementation of the key components of PCMH into practice improvement efforts and residency curricula improved residents' routine use of PCMH in patient care and their perceived PCMH competence.

Residency programs face inevitable challenges as they redesign their practices for higher quality care and resident training. Identifying and addressing early barriers can help align priorities and thereby augment the capacity to change.Evaluation of the Colorado Family Medicine Residency PCMH Project included iterative qualitative analysis of field notes, interviews, and documents to identify early barriers to change and strategies to overcome them.Nine common but not universal barriers were identified: (1) a practice's history reflected some negative past experiences with quality improvement or routines incompatible with transformative change, (2) leadership gaps were evident in unprepared practice leaders or hierarchical leadership, (3) resistance and skepticism about change were expressed through cynicism aimed at change or ability to change, (4) unproductive team processes were reflected in patterns of canceled meetings, absentee leaders, or lack of accountability, (5) knowledge gaps about the Patient-centered Medical Home (PCMH) were apparent from incomplete dissemination about the project or planned changes, (6) EHR implementation distracted focus or stalled improvement activity, (7) sponsoring organizations' constraints emerged from staffing rules and differing priorities, (8) insufficient staff participation resulted from traditional role expectations and structures, and (9) communication was hampered by ineffective methods and part-time faculty and residents. Early barriers responded to varying degrees to specific interventions by practice coaches.Some barriers that interfere with practices getting started with cultural and structural transformation can be addressed with persistent attention and reflection from on-site coaches and by realigning the talents, leaders, and priorities already in these residency programs.

Previous work using an adolescent rat model for breast cancer showed increased tumor occurrence in rats fed a chemopreventive dose of vitamin A. Preclinical models for nutrient-cancer interactions utilizing defined diets do not replicate the complexity of the human diet and may be inadequate to investigate food patterns associated with reduced cancer risk in humans. To evaluate this concept, the effects of vitamin A on sexual maturation, mammary gland development, and sensitivity to carcinogenesis were determined in the context of a human food-based diet (whole food diet). At 20 d of age (p20), female rats received either a whole-food diet with adequate levels of vitamin A, a diet with a 5.5-fold increase in vitamin A from fruits and vegetables (S diet), or a diet with a 6.2-fold increase in vitamin A provided as retinyl palmitate (RP diet). To determine the effect of dietary intervention on pubertal mammary gland development, the dietary intervention period was restricted to postnatal d 21-63. Rats were injected with 50 mg 1-methyl-1-nitrosourea/kg body weight at d 66. Compared with adolescent rats that consumed the Ad diet, consumption of S and RP diets reduced mammary cancer multiplicity (relative risk approximately 0.7, P < or = 0.002), which was associated with a reduction in alveolar gland development. The S diet suppressed the onset of sexual maturation (P < 0.001) and inhibited markers of mammary alveologenesis more than the RP diet. These data demonstrate that the amount and source of vitamin A consumed by adolescent female rats can influence the onset of puberty, mammary gland alveolar development, and breast cancer risk and highlight the relevance of utilizing whole-food diets to evaluate the role of dietary factors in cancer prevention.

Resolute Bay, a remote bay in the Canadian High Arctic to the north of Parry Channel, hosts diverse populations of marine mammals that migrate through the bay each year following food availability and/or oceanographic conditions. The changing climate combined with increasing anthropogenic activity in the Arctic make it important to create an ecosystem baseline from which to predict, understand, and monitor future changes. Passive underwater acoustic observations provide a non-invasive way to monitor marine mammal presence. Broadband noise (10 Hz to 48 kHz) was recorded by an Autonomous Marine Acoustic Recorder (AMAR) and marine mammal click detections were logged by two CPODs over a 5 month period from August to December 2013. Acoustic data were processed with click and tonal call detectors to determine marine mammal presence. Resolute Bay is ice-covered 10 months a year, leading to increased broadband ambient noise levels due to ice movement. During the short open-water period, vessel activity is common in the bay. The aim is to compare these two different ambient noise regimes and how they affect the effectiveness of passive acoustic marine mammal detections and tracking.

Results are reported from a large (n = 3,402) four-group randomized trial to increase fruit and vegetable consumption among callers to the National Cancer Institute's (NCI's) Cancer Information Service (CIS) using tailored print materials. Following a baseline telephone interview, which included a brief educational message (BEM), participants were assigned randomly within CIS offices to one of four groups: single untailored (SU) group-one untailored set of materials; single tailored (ST) group-one tailored booklet; multiple tailored (MT) group-four tailored materials; and multiple retailored (MRT) group-four tailored materials with retailoring based on new information obtained at 5 months follow-up. Follow-up telephone interviews were conducted at 5 (n = 2,233) and 12 months (n = 1,927) after baseline. The main outcome measure was self-reported fruit and vegetable consumption using a seven-item food frequency questionnaire. At 12 months follow-up, there was a significant linear trend across groups of 0.21 servings (p = 0.0002). Specific nested hypotheses then were tested and revealed significant mean serving differences between SU (5.07) vs. MT (5.64) (p = 0.002) and SU vs. MRT (5.71; p < 0.001). Although the mean for ST (5.40) was greater than that for SU (5.07), the difference was not statistically significant (p = 0.07), and no difference was found between MT vs. MRT (p = 0.69). A higher proportion of recipients of tailored materials reported reading all of the materials and believing that they were written especially for them. No differences by experimental condition were found for the perceived usefulness or motivational impact of the print materials. In this trial, MT print materials were more effective at increasing fruit and vegetable (FV) consumption than were SU materials. The intervention mechanisms responsible for this effect merit further research. Retailoring did not produce a significant difference when compared with longitudinal baseline tailoring.

It is well established that vegetables and fruit (VF) contain antioxidant phytochemicals. Consequently, it is expected that individuals who consume diets with a high content of VF should be better protected against oxidative cellular damage than individuals who do not, but not all data support this assumption. The objective of this study was to identify possible explanations for this conundrum. The effects of two diets that differed in VF content on markers of oxidative damage were studied. Sixty-four women participated in a 14-day dietary intervention. Subjects consumed on average either 3.6 or 12.1 servings of VF per day. The primary end points assessed were 8-hydroxy-2-deoxyguanosine (8-oxo-dG) in peripheral lymphocyte DNA and 8-isoprostaglandin F-2alpha (8-iso-PGF2alpha) excreted in urine. Subjects consuming the high versus low VF diet had lower concentrations of 8-oxo-dG (p < 0.01) and of 8-iso-PGF2alpha (p < 0.01). However, the reduction in oxidative end points by high VF was not uniform. Rather, an antioxidant effect was observed primarily in individuals whose oxidative end points at baseline were above the median for the study population. Using change in plasma carotenoids (end point minus baseline measurements) as an index of phytochemical intake, the reduction in oxidative markers was inversely proportional to change in plasma carotenoids; this effect was stronger for lipid peroxidation (p < 0.01) than DNA oxidation (p < 0.05). These findings imply that increasing exogenous antioxidant exposure may primarily benefit individuals with elevated levels of oxidative stress. Null findings do not necessarily indicate that an antioxidant compound lacks in vivo activity.

The goal of this study was to test the hypothesis that increased consumption of vegetables and fruit would reduce markers of oxidative cellular damage that can be assessed in blood or urine. Twenty-eight women participated in a 14 day dietary intervention. The primary end-points assessed were: 8-hydroxydeoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes, determined by HPLC with electrochemical detection; 8-OHdG excreted in urine, measured by ELISA; malondialdehyde (MDA) in urine, measured by fluorimetric detection following derivatization with thiobarituric acid and separation via HPLC; urinary 8-isoprostane F-2alpha (8-EPG) detected by ELISA. Pre- and post-intervention plasma levels of selected carotenoids were determined by HPLC. Subjects were free living and consumed a completely defined recipe-based diet that increased their average daily consumption of vegetables and fruit from 5.8 servings at baseline to 12.0 servings throughout the intervention. Overall, the level of 8-OHdG in DNA isolated from lymphocytes and in urine and the level of 8-EPG in urine were reduced by the intervention, whereas urine concentrations of MDA were minimally affected. The reduction in lymphocyte 8-OHdG was greater in magnitude (32 versus 5%) in individuals with lower average pre-intervention levels of plasma alpha-carotene (56 ng/ml) than in individuals with higher average pre-intervention plasma levels of alpha-carotene (148 ng/ml). The results of this study indicate that consumption of a diet that significantly increased vegetable and fruit intake from a diverse number of botanical families resulted in significant reductions in markers of oxidative cellular damage to DNA and lipids.

Recent collecting in the remote Pilbara region of Western Australia has revealed substantial increases in the apparent distributions of species of the genus Quistrachia, and the discovery of new forms, raising questions about the morphological taxonomy. To resolve these questions, we examined mtDNA sequences in all known species of Quistrachia, the unidentified new forms and other members of the subfamily Sinumeloninae. Phylogenetic analysis confirmed the monophyly of Quistrachia, including one of the new forms. The two other new forms represent new genera within the Sinumeloninae. Monophyly of each species was confirmed, with the exception of Q. legendrei, in which populations from the Dampier Archipelago and those from the adjacent Burrup Peninsula are in separate clades. Based on phylogeny and levels of divergence within other species in the genus, the Burrup populations appear to be conspecific with Q. turneri. This is supported by anatomical comparisons, but not by shell morphology, which may well reflect the evolutionary plasticity of shell form. Given the patchiness of searches for land snails in the largely inaccessible Pilbara region, additional species almost certainly remain to be discovered. Our study shows the value of including molecular analyses in determining the taxonomic status of new forms.