Inferring selection effects in SARS-CoV-2 with Bayesian Viral Allele Selection.

The global effort to sequence millions of SARS-CoV-2 genomes has provided an unprecedented view of viral evolution. Characterizing how selection acts on SARS-CoV-2 is critical to developing effective, long-lasting vaccines and other treatments, but the scale and complexity of genomic surveillance data make rigorous analysis challenging. To meet this challenge, we develop Bayesian Viral Allele Selection (BVAS), a principled and scalable probabilistic method for inferring the genetic determinants of differential viral fitness and the relative growth rates of viral lineages, including newly emergent lineages. After demonstrating the accuracy and efficacy of our method through simulation, we apply BVAS to 6.9 million SARS-CoV-2 genomes. We identify numerous mutations that increase fitness, including previously identified mutations in the SARS-CoV-2 Spike and Nucleocapsid proteins, as well as mutations in non-structural proteins whose contribution to fitness is less well characterized. In addition, we extend our baseline model to identify mutations whose fitness exhibits strong dependence on vaccination status as well as pairwise interaction effects, i.e. epistasis. Strikingly, both these analyses point to the pivotal role played by the N501 residue in the Spike protein. Our method, which couples Bayesian variable selection with a diffusion approximation in allele frequency space, lays a foundation for identifying fitness-associated mutations under the assumption that most alleles are neutral.

Carbon Monoxide Suppresses Neointima Formation in Transplant Arteriosclerosis by Inhibiting Vascular Progenitor Cell Differentiation.

[Figure: see text].

Dynamic interactions between apex predators reveal contrasting seasonal attraction patterns.

Apex predators play important roles in ecosystem functioning and, where they coexist, intraguild interactions can have profound effects on trophic relationships. Interactions between predators range from intraguild predation and competition to facilitation through scavenging opportunities. Despite the increased availability of fine-scale GPS data, the determinants and outcomes of encounters between apex predators remain understudied. We used simultaneous GPS data from collared spotted hyaenas (Crocuta crocuta) and African lions (Panthera leo) in Hwange National Park, Zimbabwe, to determine the environmental conditions of the encounters between the two species, which species provoked the encounter, and which species dominated the encounter. Our results show that encounters between hyaenas and lions are mostly resource-related (over a carcass or around waterholes). In the wet season, encounters mainly occur at a carcass, with lions being dominant over its access. In the dry season, encounters mainly occur in the absence of a carcass and near waterholes. Movements of hyaenas and lions before, during, and after these dry-season encounters suggest two interference scenarios: a passive interference scenario whereby both predators would be attracted to waterholes but lions would leave a waterhole used by hyaenas because of prey disturbance, and an active interference scenario whereby hyaenas would actively chase lions from waterhole areas, which are prime hunting grounds. This study highlights the seasonal dynamics of predator interactions and illustrates how the relative importance of negative interactions (interference competition during the dry season) and positive interactions (scavenging opportunities during the wet season) shifts over the course of the year.

Detection and genotypic characterization of Toxoplasma gondii DNA within the milk of Mongolian livestock.

Toxoplasma gondii is a global, zoonotic parasite capable of infecting any warm-blooded host. Toxoplasmosis can cause a variety of illnesses including abortions and congenital defects in humans, sheep, and goats. Congenital toxoplasmosis is considered to have the highest global disease burden of any foodborne illness in humans. This study examined the potential role of milk as a route of T. gondii transmission between livestock and humans within Mongolian herders, a little-studied population which relies heavily on animals. Milk of Mongolian sheep, goats and Bactrian camels was tested for the presence of T. gondii DNA, and a survey was conducted to ascertain what behavioral and environmental factors were present that might potentiate T. gondii infection within these Mongolian communities. T. gondii DNA was detected in samples from one sheep and five camels. Sequence analysis of DNA from camel milk revealed that two were from potentially virulent T. gondii genotypes. This has implications for public health in the region, as milk is an extremely important source of nutrition and our survey results imply that some people believe consumption of raw camel milk carries health benefits. This is the first report of T. gondii DNA in Bactrian camel milk as well as the first genotypic characterization of T. gondii within Mongolia.

[Inguinal hernia - review].

Inguinal hernia is the most frequently diagnosed hernia and during their lifetime one third of males are diagnosed with an inguinal hernia. The age distribution is bimodal with the highest incidence in childhood and after 50 years of age. Diagnosis is usually reached through clinical examination of a lump in the inguinal region although some patients can present with intestinal obstruction. Inguinal hernia repair is the only definitive treatment and is one of the most common surgical procedures performed. It is usually performed as an elective procedure in local, spinal or general anasthesia. The repair constitutes of reinforcing the posterior wall of the inguinal canal, often using a polypropylene mesh; either via an open anterior approach or posteriorly from within the abdomen with laparoscopy. The most common complications following a hernia repair are recurrent hernia and chronic -discomfort but recurrence rates have improved with the use of mesh and laparoscopic techniques. This evidence based review describes the -epidemiology and etiology of inguinal hernia together with the most common surgical procedures; focusing on recent innovations.

Ab interno gel implant in patients with primary open angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: To compare efficacy and safety results of an ab interno gel implant in patients with pseudoexfoliation glaucoma (PXG) and primary open angle glaucoma (POAG). METHODS: Retrospective analysis of the medical records of 110 consecutive eyes with open angle glaucoma who had received a XEN45 gel implant between March 2014 and June 2015. Intraocular pressure course, number of glaucoma medications, the need for additional intervention (including needling) and complications were evaluated until 12 months postoperatively. RESULTS: Data of 67 eyes with POAG and 43 eyes with PXG were analyzed. At 12 months postoperatively, the mean IOP had significantly decreased by 54.0% from preoperatively 31.85 ± 8.5 mmHg to 13.99 ± 2.6 mmHg in the POAG group, (p = 0.000; Wilcoxon test), and by 55.2% from 31.63 ± 9.0 mmHg to 13.28 ± 3.1 mmHg in the PXG group (p = 0.000; Wilcoxon test). The mean number of anti-glaucoma medications had significantly decreased from 3.25 ± 0.8 at baseline to 0.3 ± 0.7 medications at 12 months postoperatively in POAG eyes (p = 0.000; Wilcoxon test), and from 3.05 ± 1.0 to 0.3 ± 0.6 medications in PXG eyes (p = 0.000; Wilcoxon test). Hypotony (IOP ≤ 6 mmHg) was observed in 2 POAG eyes (3.0%) and in 5 PXG eyes (11.7%) at 1 month but normalized in all eyes at 12 months postoperatively. Severe complications were not observed. No statistically significant differences were found between PXG eyes and POAG eyes. CONCLUSION: Our data indicate that the XEN45 gel implant provides significant and comparable reduction in IOP and anti-glaucoma medication during the one-year follow-up period in POAG as well as PXG eyes. This suggests that it may be a noteworthy alternative to traditional filtering procedures in patients with POAG and PXG respectively.

Efficacy, Safety, and Risk Factors for Failure of Standalone Ab Interno Gelatin Microstent Implantation versus Standalone Trabeculectomy.

PURPOSE: To compare the efficacy, safety, and risk factors for failure of standalone ab interno gelatin microstent implantation with mitomycin C (MMC) versus trabeculectomy with MMC. DESIGN: International, multicenter, retrospective interventional cohort study. PARTICIPANTS: Three hundred fifty-four eyes of 293 patients (185 microstent and 169 trabeculectomy) with no prior incisional surgery. METHODS: Consecutive eyes with uncontrolled glaucoma underwent microstent or trabeculectomy surgery from January 1, 2011 through July 31, 2015 at 4 academic ophthalmology centers: Toronto, Canada; Frankfurt, Germany; Salzburg, Austria; and Leuven, Belgium. MAIN OUTCOME MEASURES: Primary outcome measure was hazard ratio (HR) of failure, with failure defined as 2 consecutive intraocular pressure (IOP) readings of <6 mmHg with vision loss or >17 mmHg without glaucoma medications (complete success) at least 1 month after surgery despite in-clinic interventions (including needling). Secondary outcome measures included IOP thresholds of 6 to 14 mmHg and 6 to 21 mmHg and same thresholds allowing for medications (qualified success), interventions, complications, and reoperations. RESULTS: Baseline characteristics were similar, except more men (56% vs. 43%), younger patients (average, by 3 years), better preoperative visual acuity (22% vs. 32% with 0.4 logarithm of the minimum angle of resolution vision or worse), and more trabeculoplasty (52% vs. 30%) among microstent eyes. The adjusted HR of failure of the microstent relative to trabeculectomy was 1.2 (95% confidence interval [CI], 0.7-2.0) for complete success and 1.3 (95% CI, 0.6-2.8) for qualified success, and similar for other outcomes. Time to 25% failure was 11.2 months (95% CI, 6.9-16.1 months) and 10.6 months (95% CI, 6.8-16.2 months) for complete success and 30.3 months (95% CI, 19.0-∞ months) and 33.3 months (95% CI, 25.7-46.2 months) for qualified success. Overall, white ethnicity was associated with decreased risk of failure (adjusted HR, 0.49; 95% CI, 0.25-0.96), and diabetes was associated with increased risk of failure (adjusted HR, 4.21; 95% CI, 2.10-8.45). There were 117 and 165 distinct interventions: 43% and 31% underwent needling, respectively, and 50% of trabeculectomy eyes underwent laser suture lysis. There were 22 and 30 distinct complications, although most were transient. Ten percent and 5% underwent reoperation (P = 0.11). CONCLUSIONS: There was no detectable difference in risk of failure and safety profiles between standalone ab interno microstent with MMC and trabeculectomy with MMC.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

Treeline advances and associated shifts in the ground vegetation alter fine root dynamics and mycelia production in the South and Polar Urals.

Climate warming is shifting the elevational boundary between forests and tundra upwards, but the related belowground responses are poorly understood. In the pristine South and Polar Urals with shifts of the treeline ecotone documented by historical photographs, we investigated fine root dynamics and production of extramatrical mycorrhizal mycelia (EMM) along four elevational transects reaching from the closed forest to the treeless tundra. In addition, we analysed elevational differences in climate and vegetation structure, and excavated trees to estimate related changes in the partitioning between below- and aboveground biomass. Fine root biomass of trees (<2 mm) increased by 13-79% with elevation, paralleled by a 35-72% increase in ground vegetation fine roots from the closed forest to the tundra. During the first year of decomposition, mass loss of fine root litter from different vegetation types was greater at lower elevations in the forest-tundra ecotone. The ratio between fine roots of trees and stem biomass largely increased with elevation in both regions, but these increases were not accompanied by a distinct production of EMM. Production of EMM, however, increased with the presence of ectomycorrhizal trees at the transition from the tundra to the forest. Our results imply that the recorded upward expansion of forest into former tundra in the Ural Mountains by 4-8 m per decade is decreasing the partitioning of plant biomass to fine roots. They further suggest that climate-driven forest advances will alter EMM production rates with potential feedbacks on soil carbon and nutrient cycling in these ecosystems.

[Refractive Lens Exchange]. / Refraktiver Linsenaustausch.

In refractive surgery the removal of the natural lens followed by implantation of an artificial intraocular lens has been an established method to treat refractive errors. The term "clear lens exchange" separates this approach from cataract surgery, where a cloudy lens has to be removed. With regard to currently available intraocular lens technologies, there is a wide range to correct myopia, hyperopia as well as astigmatism. Trifocal or extended depth-of-focus lenses (EDOF) even with a toric component offer the patients a potential benefit to further address presbyopia, respectively. Furthermore, the surgery in combination with Femtosecond laser-assistance offers more precision to this highly elective approach.This article provides an overview about currently available procedures and implants to correct presbyopia and refractive errors. A thorough evaluation of risk and benefit for each patient group is given with regard to recent guidelines of the German Commission for Refractive Surgery (KRC).

[Pseudophacic additive lenses]. / Pseudophake additive Intraokularlinsen.

Implantation of artificial intraocular lenses (IOL) after cataract removal today represents the standard of care in the field of anterior segment surgery. In refractive lens exchange cases the natural lens is replaced by an IOL to correct different types of refractive situations. In the majority of the operations the refractive result is satisfying with only few deviations from target refraction.But daily practice reveals some outliers from the intended corrections with the need for further refractive enhancements, respectively. Especially odd eyes with short or long axial length, corneal astigmatism, ceratoconus or after corneal laser vision correction are more or less candidates for refractive surprises. Laser corneal surgery and additional intraocular implants are both established surgical approaches to achieve this goal in pseudophacic eyes. In paediatric cataract surgery for congenital cataracts implantation of add-on lenses can be helpful to adjust refraction according to eyeball development and prevent amblyopia.This article presents an overview about currently available implants and techniques using additional lenses to correct residual refractive errors. Furthermore, new implants for special indications like macular degeneration are addressed. A thorough evaluation of risk and benefit for each patient group and materials used are provided.

Phake Intraokularlinsen.

Implanting phakic IOLs (PIOLs) in phakic eyes is regarded as an established option in refractive surgery for many years when treating high myopia, hyperopia or ametropia. Even for eyes which show a combination of refractive errors (including astigmatism) this can be an appropriate option. The surgery itself requires certain anatomical and refractive requirements, since, as with any intraocular procedure, there are different possibilities of complication depending on the chosen IOL. Therefore, any potential candidate for refractive surgery should be treated in accordance with the current recommendations of the German "Commission Refractive Surgery" (KRC) to achieve the best possible refractive outcome with maximum safety for patient and surgeon.This article will present the current options for surgery and IOLs with special focus on possibilities and limitations.

Are self-expandable metal stents superior to plastic stents in palliating malignant distal biliary strictures? A meta-analysis and systematic review.

BACKGROUND: Palliation for inoperable malignant distal biliary strictures can be achieved with self-expandable metal stents (SEMS) and plastic stents (PS). This is a meta-analysis to compare PS and SEMS. The aim of the study is to compare clinical outcomes in patients with SEMS and PS. METHODS: Study selection criteria were studied using SEMS and PS for palliation in patients with malignant distal biliary stricture. For data collection and extraction, articles were searched in Ovid journals, Medline, Cochrane database, and Pubmed. Pooled proportions were calculated using both Mantel-Haenszel method and DerSimonian Laird method for statistical analysis. RESULTS: Initial search identified 1376 reference articles, of which 112 were selected and11 studies (N = 947) were included in this analysis. Pooled analysis showed SEMS patency to be 167.7days (95% CI = 159.2-176.3) compared to 73.3days (95% CI = 69.8-76.9) in PS. SEMS have lower odds of occlusion when compared to PS with an odds ratio of 0.48 (95% CI = 0.34-0.67). SEMS has a lower odds of cholangitis compared to SP, with an odds ratio of 0.46 (95% CI = 0.30-0.69). CONCLUSION: SEMS seem to be superior to PS with better patency periods and survival duration. SEMS have lower occlusion rates, re-intervention rates, and cholangitis.

Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up.

BACKGROUND: The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. METHODS: ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55-69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50-74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years' follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. FINDINGS: With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83-1·99) after 9 years (1·64 [1·58-1·69] including France), 1·66 (1·60-1·73) after 11 years, and 1·57 (1·51-1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70-1·03) after 9 years, 0·78 (0·66-0·91) after 11 years, and 0·79 (0·69-0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490-1929) men invited for screening or one per 27 (17-66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61-0·88). INTERPRETATION: In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. FUNDING: Each centre had its own funding responsibility.

Prostate-cancer mortality at 11 years of follow-up.

BACKGROUND: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. METHODS: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. RESULTS: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality. CONCLUSIONS: Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Quality-of-life effects of prostate-specific antigen screening.

BACKGROUND: After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain. METHODS: On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled. RESULTS: Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56). CONCLUSIONS: The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.).

Do Treatment Differences between Arms Affect the Main Outcome of ERSPC Rotterdam?

PURPOSE: We assessed differences in treatment between the screening and control arms of ERSPC Rotterdam and studied whether possible treatment differences could explain the positive study outcome. MATERIALS AND METHODS: In ERSPC Rotterdam men 55 to 74 years old were randomized to a screening arm of 21,210 and a control arm of 21,166. Treatment after diagnosis was at the discretion of the care provider chosen by the patient. Initial treatment was compared in 4 risk groups. The relation between prostate cancer incidence and prostate cancer mortality was assessed by risk group by correlating the incidence RR and the mortality RR. A direct relation would have supported a stage shift as the main cause of changes in prostate cancer mortality. RESULTS: Initial treatment differed between the arms in the low, intermediate and high risk groups but not in the metastatic group. The RRs of prostate cancer incidence and mortality per risk group were related 1:1 (regression line slope 1.00, 95% CI 0.30-1.74). Of changes in prostate cancer mortality 94% could be explained by changes in prostate cancer incidence. This made treatment differences unlikely as the reason for the observed decrease in prostate cancer mortality. CONCLUSIONS: Differences in treatment between the ERSPC Rotterdam screening and control arms were unlikely to explain the differences in prostate cancer mortality. Results are instead consistent with a decrease in prostate cancer mortality as the result of a favorable stage through screening.

A longitudinal study on the impact of active surveillance for prostate cancer on anxiety and distress levels.

OBJECTIVE: Patients with potentially indolent prostate cancer (PC) can be managed with active surveillance (AS). Our objective was to analyse how anxiety and distress develop in men with untreated PC and whether highly anxious men quit AS. METHODS: One hundred and fifty Dutch patients who opted for AS in the Prostate cancer Research International: Active Surveillance Study were invited to participate in an additional prospective, longitudinal quality of life (QoL) study within 6 months after diagnosis. Participants completed questionnaires with validated measures on anxiety and distress at inclusion (t = 0), 9 (t = 9) and 18 (t = 18) months after diagnosis. We assessed changes in scores on depression (Center for Epidemiologic Studies Depression (CES-D) scale), generic anxiety (State-Trait Anxiety Inventory (STAI-6)), PC-specific anxiety (Memorial Anxiety Scale for Prostate Cancer (MAX-PC)) and decisional conflict (Decisional Conflict Scale (DCS)) about patients' treatment choice between t = 0, t = 9 and t = 18 using repeated measures analysis. RESULTS: Response rates for patients still on AS at t = 0, t = 9 and t = 18 assessments were 86%, 90% and 96%, respectively. Nine patients (7%, 9/129) between t = 0 and t = 9 and 33 of 108 patients (31%) between t = 9 and t = 18 stopped AS, mostly (86%) because of protocol-based reasons. CES-D, total MAX-PC and DCS scores did not change significantly (p > 0.05) when comparing t = 18 with t = 9 and t = 0 scores, but generic anxiety (STAI-6; p = 0.033) and fear of disease progression (sub-score of the MAX-PC; p = 0.007) decreased significantly. These differences, however, were clinically modest (0.089 SD and 0.281 SD). Overall, six of 129 men (5%) discontinued AS because of anxiety and distress. CONCLUSIONS: When men with low-risk PC are managed with AS, fear of disease progression and general anxiety decreased, and only few may discontinue AS because of anxiety and distress. This suggests that negative QoL effects are limited in men with favourable clinical characteristics who opted for AS. (Registered trial number, NTR1718) .

Initial clinical results of a new telescopic IOL implanted in patients with dry age-related macular degeneration.

PURPOSE: To evaluate the safety and efficacy of the iol-AMD technology (London Eye Hospital Pharma, London, UK), which includes two injectable, hydrophobic acrylic intraocular lenses (IOLs) in a pilot study of patients diagnosed as having cataract and dry age-related macular degeneration. METHODS: The cataract surgery and IOL implantation were performed after a preoperative evaluation using the iolAMD simulator in eyes with bilateral intermediate dry age-related macular degeneration. Outcomes were intraoperative and postoperative complications, subjective and objective visual acuity improvement, visual field changes, and postoperative diplopia. RESULTS: Three eyes of 2 patients were evaluated. The surgeries were uneventful. All eyes gained monocular reading vision at the 1-week postoperative visit. One patient with monocular implantation recognized diplopia for distance vision. Preoperative corrected distance visual acuity ranged from 20/800 to 20/125 and corrected near visual acuity was 20/800 or less. Two months after surgery, corrected distance and near visual acuities increased to levels between 20/40 and 20/25 (uncorrected distance visual acuity was 20/60 to 20/32; uncorrected near visual acuity was 20/200 to 20/25). CONCLUSIONS: These early results showed that the iolAMD simulator is a promising technology improving near and distance visual acuity in eyes with intermediate dry macular degeneration. The prismatic IOL effect did not lead to diplopia when implanted bilaterally. The surgery was safely performed.

Prevention and early detection of prostate cancer.

Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.