High-dose-rate fractionated brachytherapy monotherapy for localized prostate cancer: a systematic review and meta-analysis.

PURPOSE: High-dose-rate (HDR) brachytherapy as primary therapy (monotherapy) is a standard National Comprehensive Cancer Network (NCCN) endorsed treatment option for patients with localized prostate cancer. Thus far, most data are limited to single-institution experiences. Accordingly, we sought to systematically review rates of biochemical recurrence-free survival (bRFS) and toxicity associated with fractionated HDR monotherapy. MATERIAL AND METHODS: A systematic review was performed using PubMed and Embase databases for relevant articles published between January 1999 and December 2019, according to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Included studies were limited to fractionated HDR monotherapy publications in full manuscript form with at least 5-year median follow-up, at least 80 patients included, and adequate reporting of bRFS and toxicity data. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined using I 2 and Cochran's Q tests. RESULTS: Seven unique studies were identified, including 2,123 patients. NCCN low-, intermediate-, and high-risk patients comprised 40%, 40%, and 20% of patients, respectively. Median follow-up at the study group level was 74 months (range, 60-131 months). The 5-year bRFS rate was 95% (95% confidence interval [CI]: 93-96%), and after adjusting to control for publication bias, it was 96% (95% CI: 94-99%). Estimated adjusted late grade ≥ 3 genitourinary and gastrointestinal toxicity rates were 2% (95% CI: 1-4%) and 0.3% (95% CI: 0-1.1%), respectively. CONCLUSIONS: Fractionated HDR monotherapy is associated with high rates of disease control and low rates of toxicity. Future studies are needed to better define the value of this treatment modality relative to other options.

Null effects of therapy dog interaction on adolescent anxiety during a laboratory-based social evaluative stressor.

BACKGROUND AND OBJECTIVES: Animal-assisted interventions (AAIs) are increasingly popular as treatments to reduce anxiety. However, there is little empirical evidence testing the mechanisms of action in AAIs, especially among adolescents. We examined whether two possible mechanisms, social interaction and/or physical contact with a therapy dog, might reduce anxiety during a social stressor. DESIGN AND METHODS: To test these mechanisms, we randomly assigned 75 adolescents with low, middle, and high levels of social anxiety to complete a laboratory-based social evaluative stressor in one of three conditions: social interaction with a therapy dog (no physical interaction), social plus physical interaction with a therapy dog, or no interaction with a therapy dog. We measured self-reported anxiety and autonomic reactivity during the social stressor to assess the effects of contact with a therapy dog. RESULTS AND CONCLUSIONS: We found no evidence that the presence of a real dog, with or without the opportunity to touch it, reduced anxiety or autonomic reactivity or improved cognitive performance relative to the presence of a stuffed dog in the control condition, regardless of levels of preexisting social anxiety.Trial registration: ClinicalTrials.gov identifier: NCT03249116.

Detecting silent stressors: Trace element effects on nutritional status of declining scoter ducks of Puget Sound, USA.

White-winged scoters (Melanitta fusca; WWSC) and surf scoters (M. perspicillata; SUSC) have declined by over 60% in recent decades. Identifying contributing factors from within a mosaic of sublethal, multiple stressors is challenging. In urbanized Puget Sound, Washington, USA where scoters winter, changes in prey availability explained only a portion of local declines, suggesting that other "silent stressors" such as sublethal contaminants might play a role. Past studies of pollutant effects on scoters used Fisherian statistics that often revealed few correlates; however, novel statistical approaches could detect and provide more insights about sublethal impacts. Our objectives were to (1) relate pollutant accumulation to health of the birds, and (2) compare permutational multivariate statistics with traditional approaches in identifying sublethal health effects. We collected scoters from three locations in Puget Sound in December 2005 and March 2006, and measured cadmium (Cd), mercury (Hg), and selenium (Se) levels in livers and kidneys. To assess impacts of low contaminants levels in tissues on nutritional status (whole-body mass, lipid, and protein; and triglycerides, ß-hydroxybutyrate, and uric acid in blood), we compared statistical methods. Permutational multivariate methods use Monte Carlo techniques to assess how an integrated matrix of physiological responses in each animal respond to contaminants. Univariate regressions revealed very few and inconsistent relationships. In contrast, multivariate models showed that liver Hg and Se explained 25% of the variance in nutritional status of white-winged scoters; and in surf scoters, Cd, Hg, and Se in tissues explained 14 to 27% of nutritional status depending on site. The influence of these factors equals other aspects of habitat such as foraging conditions. Our study indicates that permutational multivariate statistics can be a powerful tool for identifying sublethal contaminant associations that, with non-contaminant stressors, can influence nutritional status and thus, contribute to population dynamics.

Lake Huron's Phosphorus Contributions to the St. Clair-Detroit River Great Lakes Connecting Channel.

The United States and Canada called for a 40% load reduction of total phosphorus from 2008 levels entering the western and central basins of Lake Erie to achieve a 6000 MTA target and help reduce its central basin hypoxia. The Detroit River is a significant source of total phosphorus to Lake Erie; it in turn has been reported to receive up to 58% of its load from Lake Huron when accounting for resuspended sediment loads previously unmonitored at the lake outlet. Key open questions are where does this additional load originate, what drives its variability, and how often does it occur. We used a hydrodynamic model, satellite images of resuspension events and ice cover, wave hindcasts, and continuous turbidity measurements at the outlet of Lake Huron to determine where in Lake Huron the undetected load originates and what drives its variability. We show that the additional sediment load, and likely phosphorus, is from wave-induced Lake Huron sediment resuspension, primarily within 30 km of the southeastern shore. When the flow is from southwest or down the center of the lake, the resuspended sediment is not detected at Canada's sampling station at the head of the St. Clair River.

Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.

Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.

Patient Self-Defined Goals: Essentials of Person-Centered Care for Serious Illness.

This research, a descriptive qualitative analysis of self-defined serious illness goals, expands the knowledge of what goals are important beyond the physical-making existing disease-specific guidelines more holistic. Integration of goals of care discussions and documentation is standard for quality palliative care but not consistently executed into general and specialty practice. Over 14 months, lay health-care workers (care guides) provided monthly supportive visits for 160 patients with advanced heart failure, cancer, and dementia expected to die in 2 to 3 years. Care guides explored what was most important to patients and documented their self-defined goals on a medical record flow sheet. Using definitions of an expanded set of whole-person domains adapted from the National Consensus Project (NCP) Clinical Practice Guidelines for Quality Palliative Care, 999 goals and their associated plans were deductively coded and examined. Four themes were identified-medical, nonmedical, multiple, and global. Forty percent of goals were coded into the medical domain; 40% were coded to nonmedical domains-social (9%), ethical (7%), family (6%), financial/legal (5%), psychological (5%), housing (3%), legacy/bereavement (3%), spiritual (1%), and end-of-life care (1%). Sixteen percent of the goals were complex and reflected a mix of medical and nonmedical domains, "multiple" goals. The remaining goals (4%) were too global to attribute to an NCP domain. Self-defined serious illness goals express experiences beyond physical health and extend into all aspects of whole person. It is feasible to elicit and record serious illness goals. This approach to goals can support meaningful person-centered care, decision-making, and planning that accords with individual preferences of late life.

Expanding the Palliative Care Domains to Meet the Needs of a Community-Based Supportive Care Model.

BACKGROUND: Whole person care is appropriate for seriously ill persons. The current framework of palliative care domains in the National Consensus Project (NCP) Guidelines for Quality Palliative Care offers an opportunity to reassess the domains of care delivered at home, earlier in the course of illness. OBJECTIVE: This qualitative study was used to test the applicability of a proposed, expanded set of domains. The results were used to inform a home-based, upstream model of supportive care for serious illness. METHODS: Quotes relating to the experience of late-life serious illness were derived from transcripts of 12 semi-structured group interviews conducted with patients, family, and professionals. Quotes originally coded to the NCP domains of palliative care were then coded to the proposed domain set, which included new categories of family/caregiver, legal/financial, and legacy/bereavement domains. RESULTS: A total of 489 quotes were assigned to the proposed expanded set of domains. One hundred one (19%) coded to the family/caregiver domain, 28 (5%) to the legacy/bereavement domain, and 27 (5%) to the legal/financial domain. Ninety-seven (87%) of the 111 quotes coded to family/caregiver had been initially coded to the NCP social aspects of care. Family/caregiver themes included challenges, rewards, insights, and family growth. CONCLUSION: The preponderance of family-related issues suggests that including the family domain may promote recognition and support of family caregivers and the services they provide. Although this study provides some support for including the legacy/bereavement and legal/financial domains, additional research is needed to determine whether there is a basis for including them in the domain structure.

Combining Best Practices and Patient, Caregiver, and Healthcare Provider Perspectives for Late-Life Supportive Care: LifeCourse.

Healthcare systems seek effective ways to support and treat the growing number of individuals living with serious illness. The nature of these care episodes challenges delivery systems to attain proficiency in dealing with the multiplicity of chronic conditions in individuals and populations through understanding and attending to patients' medical and nonmedical aspects of health. This article describes LifeCourse, a healthcare approach that provides palliative care practices to patients with serious illness years prior to death.

A metagenetic approach to determine the diversity and distribution of cyst nematodes at the level of the country, the field and the individual.

Distinct populations of the potato cyst nematode (PCN) Globodera pallida exist in the UK that differ in their ability to overcome various sources of resistance. An efficient method for distinguishing between populations would enable pathogen-informed cultivar choice in the field. Science and Advice for Scottish Agriculture (SASA) annually undertake national DNA diagnostic tests to determine the presence of PCN in potato seed and ware land by extracting DNA from soil floats. These DNA samples provide a unique resource for monitoring the distribution of PCN and further interrogation of the diversity within species. We identify a region of mitochondrial DNA descriptive of three main groups of G. pallida present in the UK and adopt a metagenetic approach to the sequencing and analysis of all SASA samples simultaneously. Using this approach, we describe the distribution of G. pallida mitotypes across Scotland with field-scale resolution. Most fields contain a single mitotype, one-fifth contain a mix of mitotypes, and less than 3% contain all three mitotypes. Within mixed fields, we were able to quantify the relative abundance of each mitotype across an order of magnitude. Local areas within mixed fields are dominated by certain mitotypes and indicate towards a complex underlying 'pathoscape'. Finally, we assess mitotype distribution at the level of the individual cyst and provide evidence of 'hybrids'. This study provides a method for accurate, quantitative and high-throughput typing of up to one thousand fields simultaneously, while revealing novel insights into the national genetic variability of an economically important plant parasite.

Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: clinical outcomes and cost analysis.

BACKGROUND: The novel oral anticoagulants (NOACs) apixaban, rivaroxaban, and dabigatran are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients with postoperative atrial fibrillation (POAF) is less well defined. METHODS: All patients undergoing isolated coronary artery bypass grafting from 2013 to 2015 (n = 598) were studied. Patients with POAF anticoagulated with either warfarin or NOACs were evaluated for differences in length of stay, blood product use, bleeding, and cost of therapy. RESULTS: There was no significant difference between the NOAC and warfarin group for any of the clinical outcomes evaluated. Time to therapeutic anticoagulation was significantly longer with warfarin. Neither group had a major bleeding event during the initial hospitalization, but 2 patients in the warfarin group had delayed major bleeding complications. Total costs were significantly reduced in patients treated with NOACs. CONCLUSIONS: Both NOACs and warfarin are safe and effective means of anticoagulation for POAF after coronary artery bypass grafting. Patients were therapeutic more rapidly and with less cost of treatment when NOACs were used.

Stopped in its tracks: how λ-cyhalothrin can break the aphid transmission of a potato potyvirus.

BACKGROUND: Pyrethroids are one of the most widespread and commonly used classes of insecticide and are used in multiple roles, including protecting potato crops from virus vector aphids. Resistance in some genotypes of a few species is now widespread, but most species remain susceptible. The rate of virus transmission by two genotypes of the peach potato aphid, Myzus persicae, fed on potato virus Y (PVY)-infected leaves of potato treated with the pyrethroid λ-cyhalothrin was evaluated. RESULTS: The susceptible genotype, type J, was significantly inhibited from transmitting virus to uninfected seedlings. A genotype containing the M918L super knockdown resistance mutation conferring resistance to pyrethroids, type O, showed no inhibition of transmission. However, when survival of the aphids after exposure was compared, the pyrethroid had not killed the type J aphids. CONCLUSIONS: λ-Cyhalothrin in a commercial formulation disrupts PVY transmission by disorienting aphid vectors for a sufficient time for the virus to lose its transmissibility. However, M. persicae genotypes carrying the M918L mutation are not prevented from transmitting.

Record-setting algal bloom in Lake Erie caused by agricultural and meteorological trends consistent with expected future conditions.

In 2011, Lake Erie experienced the largest harmful algal bloom in its recorded history, with a peak intensity over three times greater than any previously observed bloom. Here we show that long-term trends in agricultural practices are consistent with increasing phosphorus loading to the western basin of the lake, and that these trends, coupled with meteorological conditions in spring 2011, produced record-breaking nutrient loads. An extended period of weak lake circulation then led to abnormally long residence times that incubated the bloom, and warm and quiescent conditions after bloom onset allowed algae to remain near the top of the water column and prevented flushing of nutrients from the system. We further find that all of these factors are consistent with expected future conditions. If a scientifically guided management plan to mitigate these impacts is not implemented, we can therefore expect this bloom to be a harbinger of future blooms in Lake Erie.

Insecticide resistance profiles can be misleading in predicting the survival of Myzus persicae genotypes on potato crops following the application of different insecticide classes.

BACKGROUND: The accuracy of predicting the survival of insecticide-resistant aphids following the application of commonly used insecticides from the carbamate, the pyrethroid, a mix of the two or the neonicotinoid chemical classes was evaluated in a potato field in Scotland. Equal proportions of five genotypes of the peach-potato aphid, Myzus persicae (Sulzer), with none, resistance to dimethyl-carbamates, resistance to pyrethroids or combinations conferring resistance to both chemical classes were released into potato field plots. The insecticides were sprayed separately onto these plots, the aphid populations were analysed after 6-8 days and the process repeated. RESULTS: For each assessment after the three separate spray events, plots treated with the carbamate had 48, 147 and 28%, those treated with pyrethroid 53, 210 and 89%, those treated with carbamate/pyrethroid 28, 108 and 64% and those treated with neonicotinoid 43, 55 and 11% of the numbers of M. persicae by comparison with untreated controls. Only the proportions of surviving aphids from the genotype containing no insecticide resistance traits and the genotype containing elevated carboxylesterases matched ratios predicted from the selective advantage afforded by the resistance traits alone. Survival of aphids from the other three genotypes that carried 1-3 of the insecticide resistance traits differed from expectations in all cases, possibly owing to physiological differences, including their vulnerability to predators and hymenopterous parasitoids present at the site and/or their carrying unknown insecticide resistance mechanisms. CONCLUSION: Control strategies based on knowledge of the genetically determined insecticide resistance profile of an M. persicae population alone are insufficient. Hence, other important factors contributing to aphid survival under insecticide pressure need to be considered.