Development and verification of the signal to noise ratio for a layer of turbulence in a multi-layer atmosphere.

Wide-field image correction in systems that look through the atmosphere generally requires a tomographic reconstruction of the turbulence volume to compensate for anisoplanatism. The reconstruction is conditioned by estimating the turbulence volume as a profile of thin homogeneous layers. We present the signal to noise ratio (SNR) of a layer, which quantifies how difficult a single layer of homogeneous turbulence is to detect with wavefront slope measurements. The signal is the sum of wavefront tip and tilt variances at the signal layer, and the noise is the sum of wavefront tip and tilt auto-correlations given the aperture shape and projected aperture separations at all non-signal layers. An analytic expression for layer SNR is found for Kolmogorov and von Kármán turbulence models, then verified with a Monte Carlo simulation. We show that the Kolmogorov layer SNR is a function of only layer Fried length, the spatio-angular sampling of the system, and normalized aperture separation at the layer. In addition to these parameters, the von Kármán layer SNR also depends on aperture size, and layer inner and outer scales. Due to the infinite outer scale, layers of Kolmogorov turbulence tend to have lower SNR than von Kármán layers. We conclude that the layer SNR is a statistically valid performance metric to be used when designing, simulating, operating, and quantifying the performance of any system that measures properties of layers of turbulence in the atmosphere from slope data.

Robotic retroperitoneal lymph node dissection for primary and post-chemotherapy testis cancer.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer.

BACKGROUND: Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS: The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS: The cohort included 288 men with median follow-up of 82 months (interquartile range: 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65-4.24), grade progression (HR: 2.75; CI: 1.49-5.06), and volume progression (HR: 3.15; CI: 1.78-5.56). The frequency of progression to high-grade (Grade Group 4-5) tumors was not significantly different between the groups. CONCLUSIONS: Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4-5 disease.

Partial orchiectomy: The Princess Margaret cancer centre experience.

INTRODUCTION: Radical orchiectomy (RO) is the standard treatment for a testis cancer. Organ sparing surgery can be considered in the setting of a solitary functioning testis or bilateral tumors. It has also been suggested as an alternative to RO for small lesions. In this study we report our partial orchiectomy (PO) experience. METHODS: We performed a retrospective review using our prospectively maintained database analyzing PO. RESULTS: Between 1983 and 2018, 77 patients underwent PO. Mean age was 31.3 years (range 17-56). A lesion was palpable in 70 (90.9%) and median lesion size 14.1 mm (range 3-35 mm). Reasons for PO included ``small lesion" in 39 (50.6%); solitary functioning testis in 30 (39%); bilateral lesions in 6 (7.8%); or assumed benign lesion in 1 (1.3%). Median follow-up was 43.5 months (range 1-258). Lesion histology was benign in 25 (32.5%). A positive surgical margin was noted in 6 (7.8%) with none developing local or distant recurrence. Sixteen (20.8%) patients underwent salvage ipsilateral RO at a median of 3 months (range 0-46). Reasons for salvage RO included a radiologically detected lesion in 7, palpable lesion in 4, positive surgical margin in 3 and adverse pathology in 2 patients. Malignant histology was present in 12 (75%) of the salvage RO specimens. There were no reported Clavien-Dindo Grade 3 to 5 complications. CONCLUSION: Organ sparing surgery is a safe and feasible approach to small testis lesions. For the third with benign disease, and even those with malignant histology, a RO can be avoided in carefully selected patients.

Declining grouper spawning aggregations in Western Province, Solomon Islands, signal the need for a modified management approach.

Globally, groupers (Epinephelidae) that form fish spawning aggregations (FSAs) are highly vulnerable to overfishing and often require site-specific approaches to management. Over 5-years (2009-2013), we conducted underwater visual censuses (UVC) at a well-known spawning site at Njari Island, Gizo, Western Province, Solomon Islands, that supports aggregations of squaretail coralgrouper (Plectropomus areolatus), camouflage grouper (Epinephelus polyphekadion) and brown-marbled grouper (E. fuscoguttatus). Findings show that while there were species-specific variations in the duration and timing of the spawning season, aggregation densities peaked from March to June, representing the main spawning season for all three species. For P. areolatus, gonad analysis from samples taken from 2008 to 2011 confirmed reproductive activity in support of density trends observed through UVC. Over the 5-year UVC monitoring period, FSA densities declined for P. areolatus and E. polyphekadion. Conversely, following the first year of monitoring, E. fuscoguttatus densities increased. These inter-specific differences may reflect variable responses to fishing as shown elsewhere, or for example, differences in recruitment success. In response to known declines in FSAs of these species, in 2018 the Solomon Islands government placed a nationwide ban on these species' harvest and sale between October and January. As this study shows, this ban does not encompass the peak aggregation period at Njari and will offer limited protection to other FSAs of these species that are known to vary in reproductive seasonality across the Solomon Islands. A more biologically meaningful and practical management strategy would be to implement a nationwide ban on the harvest and sale of these groupers each month between full and new moons when these FSAs form consistently throughout the country. Since effective management of FSAs typically requires a combined approach, spatial management that protects both spawning sites and reproductive migratory corridors is warranted.

Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

BACKGROUND: Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity. PATIENTS AND METHODS: DNA from 210 UC patients treated with platinum-based chemotherapy was genotyped for 80 single nucleotide polymorphisms (SNPs). Logistic regression was used to examine the association between SNPs and response, and a multivariable predictive model was created. Significant SNPs were combined to form a SNP score predicting response. Eleven UC cell lines were genotyped as validation. RESULTS: Six SNPs were significantly associated with 101 complete or partial responses (48%). Four SNPs retained independence association and were incorporated into a response prediction model. Each additional risk allele was associated with a nearly 50% decrease in odds of response [odds ratio (OR) = 0.51, 95% confidence interval 0.39-0.65, P = 1.05 × 10(-7)). The bootstrap-adjusted area under the curves of this model was greater than clinical prognostic factors alone (0.78 versus 0.64). The SNP score showed a positive trend with chemosensitivity in cell lines (P = 0.115). CONCLUSIONS: Genetic variants associated with response of UC to platinum-based therapy were identified in germline DNA. A model using these genetic variants may predict response to chemotherapy better than clinical factors alone.

Reproductive biology of squaretail coralgrouper Plectropomus areolatus using age-based techniques.

The squaretail coralgrouper Plectropomus areolatus was identified as a fast-growing, early maturing and relatively short-lived aggregation-spawning epinephelid. Examinations of sectioned otoliths found females and males first maturing at 2 and 3 years, respectively, suggesting protogynous hermaphroditism; however, no transitionals were observed in samples. Age distribution for the two sexes was similar and both were represented in the oldest age class; however, significant sex-specific differences in size-at-age were identified. Both sexes fully recruit into the fishery at age 4 years and reach 90% of asymptotic length by age 3 years. Underwater visual assessments, combined with the gonado-somatic indices, revealed a 5 month reproductive season, with interannual variability observed in the month of highest density within the spawning aggregation. Catch restrictions on adults during spawning times and at reproductive sites, combined with gear-based management and enhanced enforcement, are recommended to maintain spawning stocks. Based on the available evidence, the sexual pattern for this species is unresolved.

Statin use and risk of prostate cancer and high-grade prostate cancer: results from the REDUCE study.

BACKGROUND: Statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer (PC) screening, this confounds any associations between statins and risk of being diagnosed with PC. Thus, we examined the association between statins and cancer and high-grade cancer in REDUCE, where biopsies were largely PSA-independent. METHODS: Post-hoc secondary analysis of REDUCE, which was a prospective multinational randomized controlled trial of dutasteride vs placebo for 4 years among men aged 50-75 years with PSA of 2.5-10.0 ng ml(-1) and a negative biopsy at baseline, and included PSA-independent biopsies mandated at 2- and 4-years. Analyses were limited to men who underwent at least one biopsy while under study (n=6729). The association between baseline statin use and risk of overall, high-grade (Gleason ≥ 7) or low-grade (Gleason ≤ 6) PC vs no cancer was examined using multinomial logistic regression adjusting for age, race, baseline PSA, prostate volume, rectal examination findings, body mass index (BMI), comorbidities, smoking, alcohol intake and treatment arm. RESULTS: Of 6729 men who had at least one biopsy while on study, 1174 (17.5%) were taking a statin at baseline. Men taking statins were older, had lower PSA levels, higher BMI values and lower serum testosterone and dihydrotestosterone levels, though differences, were slight. Statin use was not associated with overall PC diagnosis (multivariable OR 1.05, 95% CI 0.89-1.24, P=0.54). When stratified by grade, statin use was not associated with low-grade (multivariable OR 1.03, 95% CI 0.85-1.25, P=0.75) or high-grade cancer (multivariable OR 1.11, 95% CI 0.85-1.45, P=0.46). The major limitation is the inclusion of only men with a negative baseline biopsy. CONCLUSIONS: Among men with a negative baseline biopsy and follow-up biopsies largely independent of PSA, statins were not associated with cancer or high-grade cancer.

Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1).

BACKGROUND: To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. METHODS: Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL(-1) and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. RESULTS: A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22-1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73-1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38-2.15) (P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72-3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84-1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. CONCLUSIONS: In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.

Confidence limit variation for a single IMRT system following the TG119 protocol.

PURPOSE: To evaluate the robustness of TG119-based quality assurance metrics for an IMRT system. METHODS: Four planners constructed treatment plans for the five IMRT test cases described in TG119. All plans were delivered to a 30 cm x 30 cm x 15 cm solid water phantom in one treatment session in order to minimize session-dependent variation from phantom setup, film quality, machine performance, etc. Composite measurements utilized film and an ionization chamber. Per-field measurements were collected using a diode array device at an effective depth of 5 cm. All data collected were analyzed using the TG119 specifications to determine the confidence limit values for each planner separately and then compared. RESULTS: The mean variance of ion chamber measurements for each planner was within 1.7% of the planned dose. The resulting confidence limits were 3.13%, 1.98%, 3.65%, and 4.39%. Confidence limit values determined by composite film analysis were 8.06%, 13.4%, 9.30%, and 16.5%. Confidence limits from per-field measurements were 1.55%, 0.00%, 0.00%, and 2.89%. CONCLUSIONS: For a single IMRT system, the accuracy assessment provided by TG119-based quality assurance metrics showed significant variations in the confidence limits between planners across all composite and per-field evaluations. This observed variation is likely due to the different levels of modulation between each planner's set of plans. Performing the TG119 evaluation using plans produced by a single planner may not provide an adequate estimation of IMRT system accuracy.

Automated characterization of multiple alpha peaks in multi-site electroencephalograms.

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.

Psychometric properties of the BASIS-24© (Behaviour and Symptom Identification Scale-Revised) Mental Health Outcome Measure.

Objective. Outcome measurement in mental health services is an area of considerable clinical interest and policy priority. This study sought to assess the Behaviour and Symptom Identification Scale-24 (BASIS-24©), a brief, patient self-reported measure of psychopathology and functioning, in a UK sample, including establishing population norms for comparative purposes. Methods. Participants were 588 adults recruited from psychiatric inpatient, outpatient and primary care settings; and 630 adults randomly sampled from primary care lists who completed the BASIS-24©, and the Brief Symptom Inventory (BSI) at two time points. Results. BASIS-24© demonstrated adequate reliability (coefficient α values for combined clinical sample across subscales ranged from 0.75 to 0.91), validity and responsiveness to change (effect size for change of the BASIS-24© was 0.56 compared with 0.48 for BSI Global Severity Index). Population norms were established for the general population and adult in-patients (at in-take). The scale proved straightforward to complete across clinical settings. Variable rates of questionnaire distribution across clinical settings highlighted the ongoing challenge of incorporating outcome measures in clinical settings. Conclusion. BASIS-24© is a brief, easily administered, self-complete measure of mental well-being and functioning that adequately meets the requirements of reliability, validity and responsiveness to change required of an outcome measure.

Evaluation of the long intra-medullary hip screw.

There have been many publications about second generation femoral nails, such as the Russell-Taylor nail (Smith & Nephew Richards, Memphis, TN, USA) and Long Gamma Nail (Howmedica, Rutherford, NJ, USA), but little work has been published on the Long Intra-medullary Hip Screw (IMHS, Smith & Nephew). We set out to evaluate the effectiveness of the Long IMHS as a device for the fixation of proximal femoral fractures. We retrospectively reviewed 30 patients who had a Long IMHS inserted for a sub-trochanteric or proximal femoral fracture. Of the 30 patients, three had died and six were lost to follow up, leaving 21, whom we reviewed. Of the 21 patients reviewed the mean age was 67 years and the mean follow up was 31 weeks. Mean time to union was 15.65 weeks, with one non-union. There were three superficial wound infections. In one patient there was loosening of the distal locking screws, requiring removal and there was one case of intra-operative femoral shaft fracture. We conclude that, the Long IMHS is an effective device for the treatment of sub-trochanteric and proximal femoral fractures with a high rate of union achieved and a low complication rate.

Optimization of tumour control probability for heterogeneous tumours in fractionated radiotherapy treatment protocols.

We find the dose distribution that maximizes the tumour control probability (TCP) for a fixed mean tumour dose per fraction. We consider a heterogeneous tumour volume having a radiation response characterized by the linear quadratic model with heterogeneous radiosensitivity and repopulation rate that may vary in time. Using variational calculus methods a general solution is obtained. We demonstrate the spatial dependence of the optimal dose distribution by explicitly evaluating the solution for different functional forms of the tumour properties. For homogeneous radiosensitivity and growth rate, we find that the dose distribution that maximizes TCP is homogeneous when the clonogen cell density is homogeneous, while for a heterogeneous initial tumour density we find that the first dose fraction is inhomogeneous, which homogenizes the clonogen cell density, and subsequent dose fractions are homogeneous. When the tumour properties have explicit spatial dependence, we show that the spatial variation of the optimized dose distribution is insensitive to the functional form. However, the dose distribution and tumour clonogen density are sensitive to the value of the repopulation rate. The optimized dose distribution yields a higher TCP than a typical clinical dose distribution or a homogeneous dose distribution.

Sparing of the penile bulb and proximal penile structures with intensity-modulated radiation therapy for prostate cancer.

Quality of life is an important consideration in the treatment of early prostate cancer. Laboratory and clinical data suggest that higher radiation doses delivered to the bulb of penis and proximal penile structures correlates with higher rates of post-radiation impotence. The goal of this investigation was to determine if intensity-modulated radiation therapy (IMRT) spares dose to the penile bulb while maintaining coverage of the prostate. 10 consecutive patients with clinically organ confined prostate cancer were planned with 3D conformal radiation therapy (3D-CRT) or IMRT to give a dose of 74 Gy without specifically constraining the plans to spare the penile bulb. All 10 patients were ultimately treated with IMRT. Dose-volume histograms were evaluated and the doses to prostate, rectum, bladder and penile bulb were compared. IMRT reduced the mean penile bulb doses compared with 3D-CRT (33.2 Gy vs 48.9 Gy, p<0.001), the percentage of penile bulb receiving over 40 Gy (37.7% vs 67.2%, p<0.001) and the dose received by >95% of penile bulb (5.3 Gy vs 11.7 Gy, p=0.003). Maximum penile bulb doses were higher with IMRT (81.2 Gy vs 73.1 Gy, p<0.001) although the volume of this high dose region was small. Both methods resulted in similar coverage of the prostate. The volume of rectum receiving 70 Gy was significantly reduced with IMRT (18.4% vs 21.9%, p=0.003) but the volumes of bladder receiving 70 Gy were similar (p=0.3). IMRT may potentially reduce long term sexual morbidity by reducing the dose to the majority of the penile bulb.

A model for optimizing normal tissue complication probability in the spinal cord using a generalized incomplete repair scheme.

The purpose of this study was to determine the treatment protocol, in terms of dose fractions and interfraction intervals, which minimizes normal tissue complication probability in the spinal cord for a given total treatment dose and treatment time. We generalize the concept of incomplete repair in the linear-quadratic model, allowing for arbitrary dose fractions and interfraction intervals. This is incorporated into a previously presented model of normal tissue complication probability for the spinal cord. Equations are derived for both mono-exponential and bi-exponential repair schemes, regarding each dose fraction and interfraction interval as an independent parameter, subject to the constraints of fixed total treatment dose and treatment time. When the interfraction intervals are fixed and equal, an exact analytical solution is found. The general problem is nonlinear and is solved numerically using simulated annealing. For constant interfraction intervals and varying dose fractions, we find that optimal normal tissue complication probability is obtained by two large and equal doses at the start and conclusion of the treatment, with the rest of the doses equal to one another and smaller than the two dose spikes. A similar result is obtained for bi-exponential repair. For the general case where the interfraction intervals are discrete and also vary, the pattern of two large dose spikes is maintained, while the interfraction intervals oscillate between the smallest two values. As the minimum interfraction interval is reduced, the normal tissue complication probability decreases, indicating that the global minimum is achieved in the continuum limit, where the dose delivered by the "middle" fractions is given continuously at a low dose rate. Furthermore, for bi-exponential repair, it is seen that as the slow component of repair becomes increasingly dominant as the magnitude of the dose spikes decreases. Continuous low-dose-rate irradiation with dose spikes at the start and end of treatment yields the lowest normal tissue complication probability in the spinal cord, given a fixed total dose and total treatment time, for both mono-exponential and bi-exponential repair. The magnitudes of the dose spikes can be calculated analytically, and are in close agreement with the numerical results.

NMR evidence of pentaoxo organosilicon complexes in dilute neutral aqueous silicate solutions.

Silicon-29 NMR spectra of a neutral, dilute aqueous silicic acid solution, with a pH and Si concentration typical of soil solutions, reveal that a significant fraction of the silicon is incorporated in two five-coordinated organosilicon complexes when sodium gluconate is present.

Asymmetric preference of serine proteases toward phosphonate and phosphinate esters.

We have previously reported the asymmetric synthesis of (alpha-aminoalkyl) diphenylphosphonate and phosphinate derivatives designed as inhibitors of chymotrypsin- and elastase-like proteases. This paper reports the first kinetic evaluation of individual epimers of the (alpha-aminoalkyl) diphenylphosphonates as inactivators of chymotrypsin, cathepsin G and neutrophil elastase (HNE). Results show that the (R)-epimers consistently function as more potent irreversible inactivators of their respective target proteases than the corresponding (S)-epimers. Additionally, phosphinate analogues were found to be consistently superior to their diphenylphosphonate counterparts. For example, Cbz. Phe(P)(OPh)-(CH(2))(2)-CO(2)Et inactivates cathepsin G approximately 45-fold more rapidly (k(i)/K(i) = 1.2 x 10(5) M(-1). min(-1)) than the analogous Cbz.Phe(P)(OPh)(2) (2.6 x 10(3) M(-1). min(-1)). Similarly, Cbz.Val(P)(OPh)-(CH(2))(2)-CO(2)Et was found to inactivate HNE some 3-fold more efficiently than Cbz.Val(P)(OPh)(2) (6.5 x 10(3) and 2.0 x 10(3) M(-1). min(-1), respectively).