Quantum Zeno suppression of three-body losses in Bose-Einstein condensates

We study the possibility of suppressing three-body losses in atomic Bose-Einstein condensates via the quantum Zeno effect, which means the delay of quantum evolution by frequent measurements. It turns out that this requires very fast measurements with the rate being determined by the spatial structure of the three-body form factor, i.e., the point interaction approximation $\delta^3(\mathbf{r}-\mathbf{r'})$ is not adequate. Since the molecular binding energy $E_b$ provides a natural limit for the measurement rate, this suppression mechanism can only work if the form factor possesses certain special properties.Comment: 4 pages, 2 figure

Influence of Hospital Volume on Nephrectomy Mortality and Complications: A Systematic Review and Meta-analysis Stratified by Surgical Type

Objectives The provision of complex surgery is increasingly centralised to high volume specialist hospitals. Evidence to support nephrectomy centralisation however has been inconsistent. We conducted a systematic review and meta-analysis to determine the association between hospital case volumes and perioperative outcomes in radical nephrectomy, partial nephrectomy and nephrectomy with venous thrombectomy. Methods Medline, Embase and the Cochrane Library were searched for relevant studies published between 1990 and 2016. Pooled effect estimates for nephrectomy mortality and complications were calculated for each nephrectomy type using the DerSimonian and Laird random-effects model. Sensitivity analyses were performed to examine the effects of heterogeneity on the pooled effect estimates by excluding studies with the heaviest weighting, lowest methodological score, and most likely to introduce bias from misclassification of standardised hospital volume. Results Some 226,372 patients from sixteen publications were included in our review and meta-analysis. Considerable between-study heterogeneity was noted and only a few reported volume-outcome relationships specifically in partial nephrectomy or nephrectomy with venous thrombectomy. High volume hospitals were correlated with a 26% and 52% reduction in mortality for radical nephrectomy (OR 0.74, 95% CI 0.61-0.90, p<0.01) and nephrectomy with venous thrombectomy (OR 0.48, 95% CI 0.29-0.81, p<0.01) respectively. In addition, radical nephrectomy in high volume hospitals was associated with an 18% reduction in complications (OR 0.82, 95% CI 0.73-0.92, p<0.01). No significant volume-outcome relationship in mortality (OR 0.84, 95% CI 0.31-2.26, p=0.73) or complications (OR 0.85, 95% CI 0.55-1.30, p=0.44) was observed for partial nephrectomy. Conclusions Our findings suggest that patients undergoing radical nephrectomy have improved outcomes when treated by high volume hospitals. Evidence of this in partial nephrectomy and nephrectomy with venous thrombectomy is however not yet clear and could be secondary to the low number of studies included and the small patient number in our analyses. Further investigation is warranted to establish the full potential of nephrectomy centralisation particularly as existing evidence is of low quality with significant heterogeneity.This work was supported by Addenbrooke’s Charitable Trust, the Royal College of Surgeons of England and the Urology Foundation. Cancer Research UK Advanced Clinician Scientist Fellowship award (No. C18081/A18180) has supported GL and TS

Novel three-dimensional bone ‘mapping’ software can help assess progression of osseous metastases from routine CT

Imaging of bone metastasis response to therapy is a research priority. Stradwin is a new software-tool, with demonstrated sub-voxel accuracy in assessing cortical bone properties from routine CT. We applied this technology to the context of osseous metastases, with particular focus on disease progression using prostate cancer as a model. 3D–rendered ‘bone-maps’ were produced for 20 men with advanced prostate cancer, including a sub-cohort of 9 who had undergone serial scans. Correlation between baseline interpretation and assessments of progression between modalities was assessed. Bone-maps took significantly less time to interpret than CT bone windows (P < 0.001). Initial bone-mapping, without adjustment, demonstrated sensitivity and specificity for suspicious areas on CT of 70.7% and 73.1% respectively. Evaluating disease over time, concordance between bone-maps and current practice using RECIST outcomes was 100%. This study demonstrates the feasibility and potential use of this free post-processing software in the serial assessment of osseous metastases

Impact of Hospital Nephrectomy Volume on Intermediate to Long-term Survival in Renal Cell Carcinoma

OBJECTIVE: To evaluate the relationship between hospital volume and intermediate and long-term patient survival for patients undergoing nephrectomy for renal cell carcinoma (RCC). PATIENTS & METHODS: Adult RCC patients treated with nephrectomy between 2000 and 2010 were identified from the English Hospital Episode Statistics and National Cancer Data Repository. Patients with nodal or metastatic disease were excluded. Hospitals were categorised into low (<20/yr), medium (20-39/yr) and high (≥40/yr) volume based on annual cases of RCC nephrectomy. Multivariable Cox regressions were used to calculate hazard ratios for all-cause mortality by hospital volume, adjusting for patient, tumour and surgical characteristics. We assessed conditional survival over three follow-up periods: short (30d-1yr), intermediate (1-3yr) and long (3-5yr). We additionally explored whether associations between volume and outcomes varied by tumour stage. RESULTS: 12,912 patients were included. Patients in high volume hospitals had 34% reduction in mortality risks up to one year compared to those in low volume hospitals (HR 0.66, 95% CI 0.53-0.83, p<0.01). Assuming causality, treatment in high volume hospitals was associated with one fewer death in every 71 patients treated. Benefit of nephrectomy centralisation did not change with higher T stage (p=0.17). No significant association between hospital volume and survival was observed beyond the first year. CONCLUSIONS: RCC nephrectomy in high volume hospitals was associated with improved survival for up to one year after treatment. Our results contribute new insights regarding the value of nephrectomy centralisation. This article is protected by copyright. All rights reserved

Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1–infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy

Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1–infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy

A kapwa-infused paradigm in teaching Catholic theology/catechesis in a multireligious classroom in the Philippines

The increasing religious diversity in educational space has raised a legitimate question on how Catholic theology/ catechesis must be taught in Philippine Catholic universities given the institutional mandate to educate students “into the faith of the Church through teaching of Christian doctrine in an organic and systematic way” (Wuerl, 2013, 1). On this note, the paper makes reference to “centered plural- ism” (CP), a positional posture espoused by Georgetown University in dealing with this predicament. In an attempt to (re) appropriate CP into local context, there is a need to explore the Filipino conception of self/others as enveloped within the indigenous concept of kapwa. Hereon, the paper finds that CP is not just feasibly suitable in local context but with kapwa's more inclusive description of the relationship of self and others, a CP‐based teaching paradigm in theology/ catechesis is a promising project in the educational scene of the Philippines

Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre

Objective To investigate the clinical and pathological trends over a ten-year period for robotic-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. Patients and Methods 1500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data was collected on clinic-pathological details at presentation as well as surgical outcomes and compared over time. Results The median(range) age of patients throughout the period was 62(35-78) years. The proportion of pre-operative high-grade cases (Gleason sum 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (p<0.0001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (p<0.0001). Median PSA at diagnosis did not alter significantly. Overall 11.6% of men in 2005-2008 were classified pre-operatively as high-risk by NICE criteria, compared to 33.6% in 2013-2015 (p<0.0001). The corresponding proportions for low-risk cases were 48.6% and 17.3% respectively. Final surgical pathology demonstrated an increase in tumour stage, Gleason grade and nodal status across time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-15 (p=0.0007), Gleason grade 9-10 tumours increased from 1.8% to 9.1% (p=0.0002) and positive nodal status increased from 1.6% to 12.9% (p<0.0001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (p=0.72). Conclusion This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher-stage and more advanced disease being referred and operated on. Surgical margin outcomes however have remained good.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bju.1351

Recent Developments in Lattice QCD

I review the current status of lattice QCD results. I concentrate on new analytical developments and on numerical results relevant to phenomenology.Comment: 35 pages, 4 figures (Figures are excerpted from others' work and are not included) Uses harvmac.te

Identification of pathologically insignificant prostate cancer is not accurate in unscreened men.

BACKGROUND: Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters. METHODS: Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed. RESULTS: Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations. CONCLUSIONS: In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy