Rate of tree carbon accumulation increases continuously with tree size.

Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.

Novel approach for selective reduction of NNN in cigarette tobacco filler and mainstream smoke.

Research conducted during past decades to reduce the level of the tobacco specific nitrosamine N-nitrosonornicotine (NNN) and its precursor nornicotine in tobacco yielded identification of three tobacco genes encoding for cytochrome P450 nicotine demethylases converting nicotine to nornicotine. We carried out trials to investigate the effect of using tobaccos containing three non-functional nicotine demethylase genes on the selective reduction of NNN in cigarette tobacco filler and mainstream smoke. Our results indicate that the presence of non-functional alleles of the three genes reduces the level of nornicotine and NNN in Burley tobacco by 70% compared to the level observed in currently available low converter (LC) Burley tobacco varieties. The new technology, named ZYVERT™, does not require a regular screening process, while a yearly selection process is needed to produce LC Burley tobacco seeds for NNN reduction. The reduction of NNN observed in smoke of blended prototype cigarettes is proportional to the inclusion level of tobacco having ZYVERT™ technology. Inclusion of Burley tobacco possessing the new trait into a typical American blend resulted in a selective reduction of NNN in cigarette smoke, while the levels of other Harmful and Potentially Harmful Constituents (HPHC) currently in the abbreviated list provided by the US Food and Drug Administration are statistically equivalent in comparison with the levels obtained in reference prototype cigarettes containing LC Burley.

Rectal Ulcers and Rectoprostatic Fistulas after (125)I Low Dose Rate Prostate Brachytherapy.

PURPOSE: Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors. MATERIALS AND METHODS: We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate (125)I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation. RESULTS: At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas. CONCLUSIONS: Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.

Oral microbiome diversity among Cheyenne and Arapaho individuals from Oklahoma.

OBJECTIVES: There is a major ascertainment bias in microbiome research, with individuals of predominately European ancestry living within metropolitan areas dominating most studies. Here we present a study of the salivary microbiome within a North American Indian community. This research is the culmination of four years of collaboration and community engagement with Cheyenne & Arapaho (C&A) tribal members from western Oklahoma. MATERIALS AND METHODS: Using 16S rRNA gene amplification and next-generation sequencing, we generated microbial taxonomic inventories for 37 individuals representing five towns within the C&A tribes. For comparison, we performed the same laboratory techniques on saliva samples from 20 non-native individuals (NNI) from Norman, Oklahoma. RESULTS: The C&A participants differ from the NNI in having reduced within-individual species richness and higher between-individual variation. Unsupervised clustering analyses reveal that three ecological groupings best fit the data, and while C&A individuals include assignments to all three groups, the NNI individuals are assigned to only one group. One of the ecological groups found exclusively among C&A participants was characterized by high abundance of the oral bacterial genus Prevotella. DISCUSSION: The C&A and NNI participants from Oklahoma have notable differences in their microbiome diversity, with a wider range of variation observed among the C&A individuals, including a higher frequency of bacteria implicated in systemic disorders. Overall, this study highlights the importance of engagement with indigenous communities, and the need for an improved understanding of human microbiome diversity among underrepresented groups and those individuals living outside of metropolitan areas.

Quantifying external focus of attention in sailing by means of action sport cameras.

The aim of the current study was twofold: (1) to validate the use of action sport cameras for quantifying focus of visual attention in sailing and (2) to apply this method to examine whether an external focus of attention is associated with better performance in upwind sailing. To test the validity of this novel quantification method, we first calculated the agreement between gaze location measures and head orientation measures in 13 sailors sailing upwind during training regattas using a head mounted eye tracker. The results confirmed that for measuring visual focus of attention in upwind sailing, the agreement for the two measures was high (intraclass correlation coefficient (ICC) = 0.97) and the 95% limits of agreement were acceptable (between -8.0% and 14.6%). In a next step, we quantified the focus of visual attention in sailing upwind as fast as possible by means of an action sport camera. We captured sailing performance, operationalised as boat speed in the direction of the wind, and environmental conditions using a GPS, compass and wind meter. Four trials, each lasting 1 min, were analysed for 15 sailors each, resulting in a total of 30 upwind speed trials on port tack and 30 upwind speed trials on starboard tack. The results revealed that in sailing - within constantly changing environments - the focus of attention is not a significant predictor for better upwind sailing performances. This implicates that neither external nor internal foci of attention was per se correlated with better performances. Rather, relatively large interindividual differences seem to indicate that different visual attention strategies can lead to similar performance outcomes.

Habitat restoration affects immature stages of a wetland butterfly through indirect effects on predation.

Habitat loss worldwide has led to the widespread use of restoration practices for the recovery of imperiled species. However, recovery success may be hampered by focusing on plant communities, rather than the complex suite of direct and indirect interactions among trophic levels that occur in natural systems. Through a factorial field experiment, we tested the effects of wetland restoration on egg and juvenile survival of a locally rare butterfly, Satyrodes appalachia, via tree removal and damming. Tree removal more than tripled S. appalachia host plant abundance, but neither restoration action directly affected S. appalachia egg and juvenile survival. Instead, we found strong indirect effects of habitat manipulation on S. appalachia egg and juvenile survival that were mediated through predation. The interaction of tree removal and damming significantly decreased predation of S. appalachia eggs relative to each treatment alone. Damming alone had a significant positive indirect effect on the survival of S. appalachia juveniles, likely because increases in standing water reduced predator access. Our results emphasize the need for experiments that evaluate the demographic responses of imperiled species to habitat restoration prior to management action and quantify potential indirect effects mediated through higher trophic levels.

Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer.

BACKGROUND: The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). METHODS: Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. RESULTS: The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis. CONCLUSIONS: In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years.

Treatment options for localized prostate cancer.

OBJECTIVE: To describe treatment options for clinically localized prostate cancer: radical prostatectomy, prostate brachytherapy, external beam radiation, and active surveillance. QUALITY OF EVIDENCE: Prostate-specific antigen (PSA) outcomes presented are from non-randomized, cohort, and other comparisons trials (level II evidence). We describe PSA outcomes from Canadian centres when they are available. One small randomized controlled trial (level I evidence) in localized prostate cancer is available to compare radical prostatectomy with brachytherapy. MAIN MESSAGE: Treatment choice in prostate cancer is based on initial PSA level, clinical stage of disease, and Gleason score, together with baseline urinary function, comorbidities, and patient age. In this article, we describe patients' eligibility for and the common side effects of all treatment options. Prostate brachytherapy and active surveillance have evolved as new standard treatments of localized prostate cancer. We give a brief overview of the brachytherapy procedure, side effects, and PSA outcomes across Canada, as well as active surveillance guidelines. CONCLUSION: Prostate cancer treatment requires a multidisciplinary approach, with input from both urology and radiation oncology. Input from family physicians is often as important in helping guide patients through the treatment decision process.

An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

Multi-Frequency 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) System for the Prostate.

This article describes a novel system for quantitative and volumetric measurement of tissue elasticity in the prostate using simultaneous multi-frequency tissue excitation. Elasticity is computed by using a local frequency estimator to measure the three-dimensional local wavelengths of steady-state shear waves within the prostate gland. The shear wave is created using a mechanical voice coil shaker which transmits simultaneous multi-frequency vibrations transperineally. Radio frequency data is streamed directly from a BK Medical 8848 transrectal ultrasound transducer to an external computer where tissue displacement due to the excitation is measured using a speckle tracking algorithm. Bandpass sampling is used that eliminates the need for an ultra-fast frame rate to track the tissue motion and allows for accurate reconstruction at a sampling frequency that is below the Nyquist rate. A roll motor with computer control is used to rotate the transducer and obtain 3D data. Two commercially available phantoms were used to validate both the accuracy of the elasticity measurements as well as the functional feasibility of using the system for in vivo prostate imaging. The phantom measurements were compared with 3D Magnetic Resonance Elastography (MRE), where a high correlation of 96% was achieved. In addition, the system has been used in two separate clinical studies as a method for cancer identification. Qualitative and quantitative results of 11 patients from these clinical studies are presented here. Furthermore, an AUC of 0.87±0.12 was achieved for malignant vs. benign classification using a binary support vector machine classifier trained with data from the latest clinical study with leave one patient out cross-validation.

Limited-stage diffuse large B-cell lymphoma treated with abbreviated systemic therapy and consolidation radiotherapy: involved-field versus involved-node radiotherapy.

BACKGROUND: For limited-stage diffuse large B-cell lymphoma (DLBCL), treatment decisions are often influenced by toxicity profiles. One strategy that minimizes chemotherapy-induced toxicities is abbreviated chemotherapy plus consolidation involved-field radiotherapy (IFRT). Involved-node radiotherapy (INRT) is a new concept to DLBCL, aimed to reduce radiotherapy-induced toxicities. We retrospectively review the long-term outcomes of limited-stage DLBCL treated with abbreviated systemic therapy and radiotherapy focusing on field size: IFRT versus INRT. METHODS: The British Columbia Cancer Agency Lymphoid Cancer Database was used to identify patients diagnosed with limited-stage DLBCL (stage I/II, without B-symptoms; bulk < 10 cm) from 1981 to 2007. Patients were prescribed 3 cycles of chemotherapy plus IFRT (1981-1996) or INRT≤5 cm (1996-2007), defined as INRT to the prechemotherapy involved nodes with margins ≤ 5 cm. RESULTS: A total of 288 patients were identified: 56% were aged >60 years, 34% had stage II disease, 55% had extranodal disease, 19% had elevated lactate dehydrogenase levels, and 15% received rituximab. The two radiotherapy groups were IFRT (138 patients; 48%) and INRT≤5cm (150 patients; 52%); median follow-up was 117 and 89 months, respectively. Distant relapse was the most common site of failure in both groups. After INRT≤5 cm, marginal recurrence was infrequent (2%). Time to progression (P = .823), progression-free survival (P = .575), and overall survival (P = .417) were not significantly different between the radiotherapy cohorts. Radiotherapy field size was not a significant prognostic factor on multivariate analyses. CONCLUSIONS: This research is the first known body of work to apply the concept of INRT to limited-stage DLBCL. Reducing the field size from IFRT to INRT≤5 cm maintains a low marginal recurrence risk with no impact on overall outcome.

Incomplete testosterone suppression with luteinizing hormone-releasing hormone agonists: does it happen and does it matter?

UNLABELLED: What's known on the subject? and What does the study add? Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival. This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long-term biochemical control rates. OBJECTIVES: • To describe breakthrough rates above castrate levels of testosterone, in a population-based series of men undergoing adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy with curative radiation therapy. • To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes. PATIENTS AND METHODS: • All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible (n= 11752). Of these, 2196 fulfilled the eligibility criteria. • Serial testosterone measurements were obtained during continuous LHRH therapy. • Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course. • Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post-treatment nadir) were determined. RESULTS: • The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges). • Repeated breakthroughs occurred in 16% of patients. • Younger men were more liable to breakthroughs (P < 0.001). • Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs. • Neither overall biochemical non-evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5-year bNED in those with breakthroughs of 1.1-1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048). CONCLUSIONS: • Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome. • The monitoring of testosterone levels during therapy is therefore advised.

Prostate brachytherapy postimplant dosimetry: seed orientation and the impact of dosimetric anisotropy in stranded implants.

PURPOSE: In postimplant dosimetry for prostate brachytherapy, dose is commonly calculated using the TG-43 1D formalism, because seed orientations are difficult to determine from CT images, the current standard for the procedure. However, the orientation of stranded seeds soon after implantation is predictable, as these seeds tend to maintain their relative spacing, and orient themselves along the implant trajectory. The aim of this study was to develop a method for determining seed orientations from reconstructed strand trajectories, and to use this information to investigate the dosimetric impact of applying the TG-43 2D formalism to clinical postimplant analysis. METHODS: Using in-house software, the preplan to postimplant seed correspondence was determined for a cohort of 30 patients during routine day-0 CT-based postimplant dosimetry. All patients were implanted with stranded-seed trains. Spline curves were fit to each set of seeds composing a strand, with the requirement that the distance along the spline between seeds be equal to the seed spacing within the strand. The orientations of the seeds were estimated by the tangents to the spline at each seed centroid. Dose distributions were then determined using the 1D and 2D TG-43 formalisms. These were compared using the TG-137 recommended dose metrics for the prostate, prostatic urethra, and rectum. RESULTS: Seven hundred and sixty one strands were analyzed in total. Defining the z-axis to be cranial-positive and the x-axis to be left-lateral positive in the CT coordinate system, the average seed had an inclination of 21° ± 10° and an azimuth of -81° ± 57°. These values correspond to the average strand rising anteriorly from apex to base, approximately parallel to the midsagittal plane. Clinically minor but statistically significant differences in dose metrics were noted. Compared to the 2D calculation, the 1D calculation underestimated prostate V100 by 1.1% and D90 by 2.3 Gy, while overestimating V150 and V200 by 1.6% and 1.3%, respectively. Urethral and rectal dose quantifiers tended to be underestimated by the 1D calculation. The most pronounced differences were in the urethral D30 and rectal D2cc, which rose by 3.8 and 1.9 Gy, respectively, using the 2D calculation. The total volume of the 100% isodose region as a percentage of the prostate volume was found to increase by 0.4%. CONCLUSIONS: Stranded seeds in the supine patient are not oriented in a uniformly random manner, nor are they aligned along the axis of the CT scanner. Instead, this study identified a consistent anterior pitch that is likely attributable to differences in patient pose between implant and CT imaging. The angle of the ultrasound probe with respect to the patient during implant may have also been a contributing factor. The dose metrics derived using the 1D formalism were found to be within 2%, on average, of those derived using the 2D formalism. For greater accuracy, 2D dosimetry can be pursued using the strand-fitting method described in this work. If a 1D representation is used, integrating over the empirically determined seed orientation density reported here may be more appropriate than assuming that seed inclinations are distributed uniformly.

Registration of trans-perineal template mapping biopsy cores to volumetric ultrasound.

PURPOSE: Pathology from trans-perineal template mapping biopsy (TTMB) can be used as labels to train prostate cancer classifiers. In this work, we propose a framework to register TTMB cores to advanced volumetric ultrasound data such as multi-parametric transrectal ultrasound (mpTRUS). METHODS: The framework has mainly two steps. First, needle trajectories are calculated with respect to the needle guiding template-considering deflections in their paths. In standard TTMB, a sparsely sampled ultrasound volume is taken prior to the procedure which contains the template overlaid on top of it. The position of this template is detected automatically, and the cores are mapped following the calculated needle trajectories. Second, the TTMB volume is aligned to the mpTRUS volume by a two-step registration method. Using the same transformations from the registration step, the cores are registered from the TTMB volume to the mpTRUS volume. RESULTS: TTMB and mpTRUS of 10 patients were available for this work. The target registration errors (TRE) of the volumes using landmarks picked by three research assistants (RA) and one radiation oncologist (RO) were on average 1.32 ± 0.7 mm and 1.03 ± 0.6 mm, respectively. Additionally, on average, our framework takes only 97 s to register the cores. CONCLUSION: Our proposed framework allows a quick way to find the spatial location of the cores with respect to volumetric ultrasound. Furthermore, knowing the correct location of the pathology will facilitate focal treatment and will aid in training imaging-based cancer classifiers.

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer, a population-based analysis.

PURPOSE: To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB). METHODS AND MATERIALS: A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial. RESULTS: The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients. CONCLUSIONS: In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

The geography of demography: long-term demographic studies and species distribution models reveal a species border limited by adaptation.

Potential causes of species' geographic distribution limits fall into two broad classes: (1) limited adaptation across spatially variable environments and (2) limited opportunities to colonize unoccupied areas. Combining demographic studies, analyses of demographic responses to environmental variation, and species distribution models, we investigated the causes of range limits in a model system, the eastern border of the California annual plant Clarkia xantiana ssp. xantiana. Vital rates of 20 populations varied with growing season temperature and precipitation: fruit number and overwinter survival of 1-year-old seeds declined steeply, while current-year seed germination increased modestly along west-to-east gradients in decreasing temperature, decreasing mean precipitation, and increasing variation in precipitation. Long-term stochastic finite rate of increase, λ(s), exhibited a fourfold range and varied among geologic surface materials as well as with temperature and precipitation. Growth rate declined significantly toward the eastern border, falling below 1 in three of the five easternmost populations. Distribution models employing demographically important environmental variables predicted low habitat favorability beyond the eastern border. Models that filtered or weighted population presences by λ(s) predicted steeper eastward declines in favorability and assigned greater roles in setting the distribution to among-year variation in precipitation and to geologic surface material. These analyses reveal a species border likely set by limited adaptation to declining environmental quality.

Prostate brachytherapy postimplant dosimetry: automatic plan reconstruction of stranded implants.

PURPOSE: Plan reconstruction for permanent implant prostate brachytherapy is the process of determining the correspondence between planned and implanted seeds in postimplant analysis. Plan reconstruction informs many areas of brachytherapy quality assurance, including the verification of seed segmentation, misplacement and migration assessment, implant simulations, and the dosimetry of mixed-activity or mixed-species implants. METHODS: An algorithm has been developed for stranded implants which uses the interseed spacing constraints imposed by the suture to improve the accuracy of reconstruction. Seventy randomly selected clinical cases with a mean of 23.6 (range 18-30) needles and mean density of 2.0 (range 1.6-2.6) 2.0 (range 1.6-2.6) seeds/cm3 were automatically reconstructed and the accuracy compared to manual reconstructions performed using a custom 3D graphical interface. RESULTS: Using the automatic algorithm, the mean accuracy of the assignment relative to manual reconstruction was found to be 97.7 +/- 0.5%. Fifty-two of the 70 cases (74%) were error-free; of seeds in the remaining cases, 96.7 +/- 0.3% were found to be attributed to the correct strand and 97.0 +/-0.3% were correctly connected to their neighbors. Any necessary manual correction using the interface is usually straightforward. For the clinical data set tested, neither the number of seeds or needles, average density, nor the presence of clusters was found to have an effect on reconstruction accuracy using this method. CONCLUSIONS: Routine plan reconstruction of stranded implants can be performed with a high degree of accuracy to support postimplant dosimetry and quality analyses.

Prostate implant reconstruction from C-arm images with motion-compensated tomosynthesis.

PURPOSE: Accurate localization of prostate implants from several C-arm images is necessary for ultrasound-fluoroscopy fusion and intraoperative dosimetry. The authors propose a computational motion compensation method for tomosynthesis-based reconstruction that enables 3D localization of prostate implants from C-arm images despite C-arm oscillation and sagging. METHODS: Five C-arm images are captured by rotating the C-arm around its primary axis, while measuring its rotation angle using a protractor or the C-arm joint encoder. The C-arm images are processed to obtain binary seed-only images from which a volume of interest is reconstructed. The motion compensation algorithm, iteratively, compensates for 2D translational motion of the C-arm by maximizing the number of voxels that project on a seed projection in all of the images. This obviates the need for C-arm full pose tracking traditionally implemented using radio-opaque fiducials or external trackers. The proposed reconstruction method is tested in simulations, in a phantom study and on ten patient data sets. RESULTS: In a phantom implanted with 136 dummy seeds, the seed detection rate was 100% with a localization error of 0.86 ± 0.44 mm (Mean ± STD) compared to CT. For patient data sets, a detection rate of 99.5% was achieved in approximately 1 min per patient. The reconstruction results for patient data sets were compared against an available matching-based reconstruction method and showed relative localization difference of 0.5 ± 0.4 mm. CONCLUSIONS: The motion compensation method can successfully compensate for large C-arm motion without using radio-opaque fiducial or external trackers. Considering the efficacy of the algorithm, its successful reconstruction rate and low computational burden, the algorithm is feasible for clinical use.

Evaluation of Septoria Nodorum Blotch (SNB) Resistance in Glumes of Wheat (Triticum aestivum L.) and the Genetic Relationship With Foliar Disease Response.

Septoria nodorum blotch (SNB) is a necrotrophic disease of wheat prominent in some parts of the world, including Western Australia (WA) causing significant losses in grain yield. The genetic mechanisms for resistance are complex involving multiple quantitative trait loci. In order to decipher comparable or independent regulation, this study identified the genetic control for glume compared to foliar resistance across four environments in WA against 37 different isolates. High proportion of the phenotypic variation across environments was contributed by genotype (84.0% for glume response and 82.7% for foliar response) with genotype-by-environment interactions accounting for a proportion of the variation for both glume and foliar response (14.7 and 16.2%, respectively). Despite high phenotypic correlation across environments, most of the eight and 14 QTL detected for glume and foliar resistance using genome wide association analysis (GWAS), respectively, were identified as environment-specific. QTL for glume and foliar resistance neither co-located nor were in LD in any particular environment indicating autonomous genetic mechanisms control SNB response in adult plants, regulated by independent biological mechanisms and influenced by significant genotype-by- environment interactions. Known Snn and Tsn loci and QTL were compared with 22 environment-specific QTL. None of the eight QTL for glume or the 14 for foliar response were co-located or in linkage disequilibrium with Snn and only one foliar QTL was in LD with Tsn loci on the physical map. Therefore, glume and foliar response to SNB in wheat is regulated by multiple environment-specific loci which function independently, with limited influence of known NE-Snn interactions for disease progression in Western Australian environments. Breeding for stable resistance would consequently rely on recurrent phenotypic selection to capture and retain favorable alleles for both glume and foliar resistance relevant to a particular environment.

Regional differences in awareness and attitudes regarding genetic testing for disease risk and ancestry.

Little is known about the lay public's awareness and attitudes concerning genetic testing and what factors influence their perspectives. The existing literature focuses mainly on ethnic and socioeconomic differences; however, here we focus on how awareness and attitudes regarding genetic testing differ by geographical regions in the US. We compared awareness and attitudes concerning genetic testing for disease risk and ancestry among 452 adults (41% Black and 67% female) in four major US cities, Norman, OK; Cincinnati, OH; Harlem, NY; and Washington, DC; prior to their participation in genetic ancestry testing. The OK participants reported more detail about their personal ancestries (p = 0.02) and valued ancestry testing over disease testing more than all other sites (p < 0.01). The NY participants were more likely than other sites to seek genetic testing for disease (p = 0.01) and to see benefit in finding out more about one's ancestry (p = 0.02), while the DC participants reported reading and hearing more about genetic testing for African ancestry than all other sites (p < 0.01). These site differences were not better accounted for by sex, age, education, self-reported ethnicity, religion, or previous experience with genetic testing/counseling. Regional differences in awareness and attitudes transcend traditional demographic predictors, such as ethnicity, age and education. Local sociocultural factors, more than ethnicity and socioeconomic status, may influence the public's awareness and belief systems, particularly with respect to genetics.