With a median follow-up of 13 years, a randomized comparison of radiotherapy with or without antiandrogen therapy in patients with a rising PSA level after prostatectomy showed that 2 years of ...antiandrogen therapy resulted in a significantly higher overall survival rate.
Patients with localized prostatic cancer are often treated with radical prostatectomy. More than 30% of such patients will subsequently have recurrence. This recurrence manifests first as a rising serum level of prostate-specific antigen (PSA),
1
–
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termed biochemical recurrence. Large, retrospective studies suggest that salvage radiation therapy after biochemical recurrence may be associated with long-term freedom from cancer recurrence.
4
,
5
However, 50% of the patients who are treated with salvage radiation therapy will have further disease progression, particularly when there are aggressive disease features.
4
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The combination of radiation therapy and either androgen-deprivation therapy or antiandrogen therapy prolongs survival among some . . .
Stress within tree roots may influence whole-tree responses to nutrient deficiencies or toxic ion accumulation, but the mechanisms that govern root responses to the belowground chemical environment ...are poorly quantified. Currently, root production is modeled using rates of forest production and stoichiometry, but this approach alone may be insufficient to forecast variability in forest responses when physical and chemical stressors alter root lifespan, rooting depth or mycorrhizal colonization directly. Here, we review key research priorities for improving predictions of tree responses to changes in the belowground biogeochemical environment resulting from nitrogen deposition, including: limits of the optimum allocation paradigm, root physiological stress and lifespan, contingency effects that determine threshold responses across broad gradients, coupled water-biogeochemical interactions on roots, mycorrhizal dynamics that mediate root resilience and model frameworks to better simulate root feedbacks to aboveground function. We conclude that models incorporating physiological feedbacks, dynamic responses to coupled stressors, mycorrhizal interactions, and which challenge widely-accepted notions of optimum allocation, can elucidate potential thresholds of tree responses to biogeochemical stressors. Emphasis on comparative studies across species and environmental gradients, and which incorporates insights at the cellular and ecosystem level, is critical for forecasting whole-tree responses to altered biogeochemical landscapes.
Metastasis-free survival (MFS), but not event-free survival, is a validated surrogate end point for overall survival (OS) in men treated for localized prostate cancer. It remains unknown if this ...holds true in biochemically recurrent disease after radical prostatectomy. Leveraging NRG/RTOG 9601, we aimed to determine the performance of intermediate clinical end points (ICEs) as surrogate end points for OS in recurrent prostate cancer.
NRG/RTOG 9601 randomly assigned 760 men with recurrence after prostatectomy to salvage radiation therapy with 2 years of placebo versus bicalutamide 150 mg daily. ICEs assessed were biochemical failure (BF) per NRG/RTOG 9601 (prostate-specific antigen nadir + 0.3-0.5 ng/mL or initiation of salvage hormone therapy; BF1) and NRG/RTOG 0534 (prostate-specific antigen nadir+2 ng/mL; BF2), distant metastasis (DM), and MFS (DM or death). Surrogacy was assessed by the Prentice criteria and a two-stage meta-analytic approach (condition one assessed at the patient level with Kendall's τ and condition two assessed by randomly dividing the entire trial cohort into 10 pseudo trial centers and calculating the average
between treatment hazard ratios for ICE and OS).
BF1, BF2, DM, and MFS satisfied the four Prentice criteria. However, with the two-condition meta-analytic approach, there was strong correlation between MFS and OS (τ = 0.86), moderate correlation between DM and OS (τ = 0.66), and weaker correlation between BF1 (τ = 0.25) or BF2 (τ = 0.40) and OS. Similarly, for condition two, the treatment effect of antiandrogen therapy on MFS and OS were correlated (
= 0.67), but this was not true for BF1 (
= 0.09), BF2 (
= 0.12), or DM (
= 0.18) and OS.
MFS is also a strong surrogate for OS in men receiving salvage radiation therapy for recurrence after prostatectomy. Caution should be used when inferring survival benefit from effects on BF in biochemically recurrent prostate cancer. Lack of comorbidity data did not allow us to assess whether BF in men with no/minimal comorbidity could serve as a surrogate for OS.
The RecJ exonuclease from Escherichia coli degrades single-stranded DNA (ssDNA) in the 5′–3′ direction and participates in homologous recombination and mismatch repair. The experiments described here ...address RecJ's substrate requirements and reaction products. RecJ complexes on a variety of 5′ single-strand tailed substrates were analyzed by electrophoretic mobility shift in the absence of Mg2+ ion required for substrate degradation. RecJ required single-stranded tails of 7 nt or greater for robust binding; addition of Mg2+ confirmed that substrates with 5′ tails of 6 nt or less were poor substrates for RecJ exonuclease. RecJ is a processive exonuclease, degrading ∼1000 nt after a single binding event to single-strand DNA, and releases mononucleotide products. RecJ is capable of degrading a single-stranded tail up to a double-stranded junction, although products in such reactions were heterogeneous and RecJ showed a limited ability to penetrate the duplex region. RecJ exonuclease was equally potent on 5′ phosphorylated and unphosphorylated ends. Finally, DNA binding and nuclease activity of RecJ was specifically enhanced by the pre-addition of ssDNA-binding protein and we propose that this specific interaction may aid recruitment of RecJ.
Communication skills and professionalism are two competencies in graduate medical education that are challenging to evaluate. We aimed to develop, test and validate a de novo instrument to evaluate ...these two competencies.
Using an Objective Standardized Clinical Examination (OSCE) based on a medication error scenario, we developed an assessment instrument that focuses on distinctive domains context of discussion, communication and detection of error, management of error, empathy, use of electronic medical record (EMR) and electronic medical information resources (EMIR), and global rating. The aim was to test feasibility, acceptability, and reliability of the method.
Faculty and standardized patients (SPs) evaluated 56 trainees using the instrument. The inter-rater reliability of agreement between faculty was substantial (Fleiss k = 0.71) and intraclass correlation efficient was excellent (ICC = 0.80). The measured agreement between faculty and SPs evaluation of resident was lower (Fleiss k = 0.36). The instrument showed good conformity (ICC = 0.74). The majority of the trainees (75 %) had satisfactory or higher performance in all six assessed domains and 86 % found the OSCE to be realistic. Sixty percent reported not receiving feedback on EMR use and asked for subsequent training.
An OSCE-based instrument using a medical error scenario can be used to assess competency in professionalism, communication, using EMRs and managing medical errors.
OBJECTIVE To assess emergency physicians' diagnostic approach to the patient with dizziness, using a multicenter quantitative survey. PARTICIPANTS AND METHODS We anonymously surveyed attending and ...resident emergency physicians at 17 academic-affiliated emergency departments with an Internet-based survey (September 1, 2006, to November 3, 2006). The survey respondents ranked the relative importance of symptom quality, timing, triggers, and associated symptoms and indicated their agreement with 20 statements about diagnostic assessment of dizziness (Likert scale). We used logistic regression to assess the impact of “symptom quality ranked first” on odds of agreement with diagnostic statements; we then stratified responses by academic rank. RESULTS Of the 505 individuals surveyed, 415 responded for an overall response rate of 82%. A total of 93% (95% confidence interval CI, 90%-95%) agreed that determining type of dizziness is very important, and 64% (95% CI, 60%-69%) ranked symptom quality as the most important diagnostic feature. In a multivariate model, those ranking quality first (particularly resident physicians) more often reported high-risk reasoning that might predispose patients to misdiagnosis (eg, in a patient with persistent, continuous dizziness, who could have a cerebellar stroke, resident physicians reported feeling reassured that a normal head computed tomogram indicates that the patient can safely go home) (odds ratio, 6.74; 95% CI, 2.05-22.19). CONCLUSION Physicians report taking a quality-of-symptoms approach to the diagnosis of dizziness in patients in the emergency department. Those relying heavily on this approach may be predisposed to high-risk downstream diagnostic reasoning. Other clinical features (eg, timing, triggers, associated symptoms) appear relatively undervalued. Educational initiatives merit consideration.
External irradiation of epithelial skin cancer Lovett, R D; Perez, C A; Shapiro, S J ...
International journal of radiation oncology, biology, physics,
08/1990, Letnik:
19, Številka:
2
Journal Article
Recenzirano
A total of 339 consecutively treated, biopsy proven squamous and basal cell carcinomas of the skin treated from January 1966 to December 1986 were retrospectively analyzed to determine the patterns ...of local recurrence. There were 242 basal cell carcinomas, 92 squamous cell carcinomas, and 5 variants of squamous cell carcinoma in various locations. Radiotherapy was the initial treatment modality in 212 patients and 127 were treated after failing initial surgical excision. Lymph nodes were involved in 1/242 patients (.4%) with basal cell carcinoma, 14/92 patients (15%) with initially treated squamous cell carcinoma, and 20/51 (39%) with recurrent squamous cell lesions. Distant metastasis was found in one patient. Superficial X rays were given to 187 patients, electrons to 57 patients, megavoltage photons to 15, and a combination of modalities to the remainder. Overall local tumor control was achieved in 292 of 339 patients (86%), 220 of 242 (91%) with basal cell and 73 of 97 (75%) with squamous cell carcinoma. Tumor control was closely related to the size of the primary lesion. For lesions less than 1 cm tumor control was 97% (86/89) for basal cell and 91% (21/23) for squamous cell carcinoma. For 1 to 5 cm, tumor control was 87% (116/133) for basal cell and 76% (39/51) for squamous cell carcinoma and for lesions greater than 5 cm, the tumor control was 87% (13 of 15) and 56% (9/16), respectively. Tumor control was related to the modality used to treat the patient in spite of stratification of primary lesion size. For superficial X rays, tumor control was 98% (81/83) for lesions less than 1 cm, 93% (94/101) for lesions 1-5 cm and 100% (5/5) for lesions greater than 5 cm. For electrons tumor control was 88% (14/16), 72% (23/32), and 78% (7/9), respectively. For mixed beams tumor control was 90% (9/10), 76% (32/42), and 64% (9/14), respectively, and for 60Co-4 MV X rays, tumor control was 100% (3/3), 67% (6/9), and 33% (1/3), respectively. Cosmesis and complications were analyzed in 261 patients. An excellent or good cosmetic result was found in 92% (239/261) of the patients. There were 8 of 261 patients (3.1%) with fair and 19 of 261 (7.3%) with poor cosmesis. Cosmesis had an inverse relation to the primary lesion size with 97 of 99 patients (98%) with tumors 1 cm or less, 123 of 140 patients (88%) with lesions 1 to 5 cm and 13 of 16 patients (82%) with larger tumors having excellent or good cosmetic results. Cosmesis is also related to treatment modality.
The Escherichia coli recJ gene product was overproduced using a plasmid that carries the recJ gene downstream of a strong regulatable promoter and a strong ribosome-binding site. Overexpression of ...recJ produced a concomitant increase in the levels of single-stranded-DNA-specific nuclease activity present in crude cell extracts. This nuclease activity was purified to homogeneity and found to reside in a 60-kDa polypeptide. This polypeptide was induced with recJ overexpression and had the size and N-terminal amino acid sequence identical to the predicted RecJ protein sequence. The RecJ nuclease degraded linear single-stranded DNA but did not have exonuclease activity on linear double-stranded substrates or endonuclease activity on either single-stranded or double-stranded substrates. The RecJ exonuclease had greater activity on duplex DNA molecules with 5′-rather than 3′-single-stranded tails.
Background: Epidemiologic studies have linked fine particulate air pollution with cardiopulmonary mortality, yet underlying biologic mechanisms remain unknown. Changes in heart rate variability (HRV) ...may reflect changes in cardiac autonomic function and risk of sudden cardiac death. This study evaluated changes in mean heart rate and HRV in human beings associated with changes in exposure to particulate air pollution. Methods: Repeated ambulatory electrocardiographic monitoring was conducted on 7 subjects for a total of 29 person-days before, during, and after episodes of elevated pollution. Mean HR, the standard deviation of normal-to-normal (NN) intervals (SDNN), the standard deviation of the averages of NN intervals in all 5-minute segments of the recording (SDANN), and the square root of the mean of squared differences between adjacent NN intervals (r-MSSD) were calculated for 24-hour and 6-hour time segments. Associations of HRV with particulate pollution levels were evaluated with fixed-effects regression models. Results: After controlling for differences across patients, elevated particulate levels were associated with (1) increased mean HR, (2) decreased SDNN, a measure of overall HRV, (3) decreased SDANN, a measure that corresponds to ultralow frequency variability, and (4) increased r-MSSD, a measure that corresponds to high-frequency variability. The associations between HRV and particulates were small but persisted even after controlling for mean HR. Conclusions: This study suggests that changes in cardiac autonomic function reflected by changes in mean HR and HRV may be part of the pathophysiologic mechanisms or pathways linking cardiovascular mortality and particulate air pollution. (Am Heart J 1999;138:890-9.)
Long-term thermal sensitivity of Earth's tropical forests Lewis, Simon L; Castilho, Carolina; Costa, Flávia ...
Science (American Association for the Advancement of Science),
05/2020, Letnik:
368, Številka:
6493
Journal Article, Web Resource
Recenzirano
Odprti dostop
The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if ...such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (-9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth's climate.
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