Lime-rich and lime-poor coastal dunes: Natural blowout activity differs with sensitivity to high N deposition through differences in P availability to the vegetation.

In industrialized countries, biodiversity is threatened by high atmospheric N deposition. In coastal dunes, blowouts can mitigate this through deposition of fresh sand, but lime-rich and lime-poor dunes may differ in blowout activity. We studied natural blowout activity and explanatory factors in 2000 and 2014 in up to 51 sites along the Dutch coast, representative for other parts of Europe. We further analyzed plant and soil characteristics related to P nutrition in seven sites in 2019 and found that blowout activity was intrinsically linked to interactions between the geosphere, pedosphere and biosphere. Blowout activity was higher in lime-rich than in lime-poor dunes, especially in 2014. This difference could not be explained by wind velocity and only partly by position in the landscape, but was associated with pH, critical N load and rabbit density. At high pH, P availability to the vegetation was low. Arbuscular mycorrhizal (AM) plant species thus predominated, which belong to the most characteristic dune plants and may provide rabbit food of better quality than nonmycorrhizal (NM) or ericoid mycorrhizal (ErM) plants. Root biomass was also low at high pH, which may reduce cohesion of the sand and increase blowout activity, especially in areas with high rabbit density. At low pH, P availability increased, which favored NM and ErM rather than AM plants, and root biomass increased, which increased stability of the blowouts. As a restoration measure, (re)activation of blowouts may improve buffer capacity, characteristic biodiversity and conservation status of coastal dune grasslands. However, lime-poor dunes are more vulnerable to acidification, increase in P availability and blowout stabilization than lime-rich dunes. In extremely lime-poor dunes, it may even be better to let vegetation develop towards Dune heathlands, which are also EU priority habitats.

The prostate cancer detection rates of CEUS-targeted versus MRI-targeted versus systematic TRUS-guided biopsies in biopsy-naïve men: a prospective, comparative clinical trial using the same patients.

BACKGROUND: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies. METHODS/DESIGN: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols. DISCUSSION: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification. TRIAL REGISTRATION: The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project.

PURPOSE: To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). METHODS: An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. RESULTS: mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. CONCLUSIONS: The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.

Surveillance following Focal Therapy interventions.

OBJECTIVE: Focal therapy (FT) is a tissuesparing treatment paradigm for localized prostate cancer (PCa) with the potential to improve functional outcomes while maintaining oncologic safety. This paper aims to provide an overview of important considerations and practical recommendations relating to the follow-up after FT. METHODS: Literature review of papers related to FT in PCa derived from Medline/Pubmed database. RESULTS: The recommended minimum follow-up period after FT is 5 years. Standard history taking should include: signs of disease progression, treatment-related complications and psychological aspects. Oncological outcome is based on serial prostate specific antigen monitoring, follow-up imaging (most commonly with multiparametric magnetic resonance imaging) and repeat biopsies (systematic from entire gland or targeted from treated zone). Significant PCa has been found at biopsy in up to 17% of patients after FT. Functional outcomes are evaluated using standardized questionnaires that relate to urinary function, erectile function and quality of life. A systematic review reports urinary continence in 83-100% of patients, erections sufficient for penetration in 54-100%. Outcomes differ between ablative energies and treatment templates. The most common side effects after FT are urinary retention (0-17%), urinary tract infection (UTI) (0-17%) and urinary stricture (0-5%). Rectal fistula is a rare complication occurring in up to 0.1-2% of patients. Clavien-Dindo Grade 3-4 complications are reported in 0-4% of patients. Type and rate vary with treatment modality. Complications should be reported using standardized reporting systems. Most data on FT outcomes come from small heterogeneous trials. Pooling of standardized data is necessary to advance the field of FT. CONCLUSION: Stringent follow-up after FT is required to confirm oncologic safety of the individual patient. Standardized data gathering and data pooling is necessary to evaluate whether FT can live up to its promise of improving functional outcomes while maintaining oncological safety.

Irreversible electroporation, a new modality in Focal Therapy for prostate cancer.

The extensive use of prostate-specific antigen (PSA) testing and improved imaging technologies have resulted in an increased diagnosis of prostate cancer. Early diagnosis is often accompanied by an increased number of localized (i.e. unifocal or unilateral), small-volume and low-grade prostate cancers. Focal therapy is an emerging treatment option in prostate cancer, targeting individual cancer areas while sparing important functional and anatomical urological structures. Irreversible electroporation is an innovative treatment modality in focal therapy based on the process of cell membrane electroporation limiting damage to adjacent tissue and vital structures. The first phase I-II trials in humans have shown the safety of IRE for focal ablative therapy of prostate cancer and showed encouraging results considering functional preservation. Histological analysis after IRE showed fibrosis without glandular ducts and necrotic tissue with sharp demarcation between unaffected prostatic glandular tissue and the ablation zone. Short-term oncological results are promising; however more data on long-term oncological outcomes are necessary. New studies with IRE and other focal treatment modalities are initiated to explore opportunities for focal therapy in prostate cancer and to optimize current treatment protocols.

Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study.

PURPOSE: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy.

OBJECTIVES: Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. METHODS: A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H&E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. RESULTS: Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. CONCLUSIONS: mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. KEY POINTS: • mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.

[Advances in ultrasound techniques for the diagnosis and staging of prostate cancer. Elastography, Doppler ultrasound, ultrasound contrast media, ultrasound quantification media and MRI fusion]. / Avances en las Técnicas Ecográficas para el diagnóstico y estadiaje del cáncer de próstata. Elastografía, Ecografía doppler, Contrastes Ecográficos, Métodos de Cuantificación ecográfica y fusión con Resonancia Magnética Nuclear.

OBJECTIVES: Transrectal ultrasound-guided prostate biopsy remains the gold standard in the diagnosis of prostate cancer. Various Ultrasound modalities have been proposed to increase the cancer detection rate. Our purpose is to evaluate each of these methods , and to present its current literature and clinical utility. METHOD: A non structured review of the current literature was conducted over these different various ultrasound modalities used during the transrectal ultrasound-guided prostate biopsied in the diagnosis of prostate cancer. RESULTS: The data investigation of the various modalities associated sonographic features exhibits great heterogeneity and highly variable results. Some new techniques sampling present promising results with high sensitivity and specificity, thus increasing the diagnostic yield of transrectal biopsy. It seems that elastography shows encouraging figures, especially given the recent introduction of the "shearvawe" elastography that decreases the user-dependent factor. CONCLUSIONS: The ultrasound-guided prostate biopsy has an acceptable sensitivity in the diagnosis of prostate cancer, but its specificity is still low. Various modalities associated with ultrasound are available in clinical practice in order to increase cancer detection rate. Although some promising data have been published for some of the modalities, we believe the combination of these includes validated ultrasound guided biopsy protocols to accurately target and diagnose prostate cancer.

Estimating the undetected burden of influenza hospitalizations in children.

During the 2004-2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT-PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture-recapture analyses to estimate the burden of influenza related-hospitalizations in children aged<5 years. During the 2004-2005 influenza season the influenza-related hospitalization rate estimated by capture-recapture analysis was 8.6/10,000 children aged<5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture-recapture analysis provides better estimates than either system alone.

Challenges in the development, licensure, and use of combination vaccines.

Before substantial public health benefits associated with use of combination vaccines can be realized, a variety of challenges must be addressed. In February 2000, the National Vaccine Program Office convened the International Symposium on Combination Vaccines to explore solutions for barriers to development, licensure, and use of safe and effective combination vaccines. The symposium focused on the following questions: (1) What immunologic standards should be used to evaluate new combination vaccines? (2) How should correlates of protection be developed, and how should the data they provide be interpreted? (3) What sample size is adequate for prelicensure safety trials of combination vaccines? (4) Should standards for evaluation of combination vaccines containing licensed components be different from standards for evaluation of combinations containing unlicensed components? (5) How can the "great expectations" of postlicensure surveillance be realized? Available data relevant to these issues were presented, providing a foundation for furthering the science of combination vaccines.

Adult immunization programs in nontraditional settings: quality standards and guidance for program evaluation.

This report provides a summary of the National Vaccine Advisory Committee's (NVAC) workshop on adult immunization programs in nontraditional settings, quality standards for such programs, and guidance for program evaluation. Throughout the United States, an increasing number of adults are receiving vaccine in nontraditional settings (e.g., pharmacies and churches). Immunization programs in nontraditional settings are often more accessible and convenient than a health-care provider's office or a public health clinic, especially for medically underserved adults (e.g., economically disadvantaged, inner city, and minority populations). Medically underserved adults might be at particular risk for undervaccination because they are often without a medical home (i.e., a regular point of contact where their health-care needs are met). Immunization programs in nontraditional settings might enhance the capacity of the health-care system to effectively deliver vaccine to adults by increasing the number and types of sites where adults can receive vaccine. NVAC has recognized that strategies need to be developed to make vaccines available to all adults and that the number of immunization programs in nontraditional settings is increasing. Therefore, the Committee issues the following report, including quality standards and guidance for program evaluation.

Reinforced poly(L-lactic acid) fibres as suture material.

In this study, reinforced poly(L-lactic acid) (PLLA) fibers made by a dry-spinning/hot-drawing process were evaluated for use as a suture. The initial tensile strength of the PLLA fibers was lower than the initial tensile strength of the commercially available sutures: PDS, Vicryl, silk, and Ethilon. However, after 12 weeks immersion in a phosphate saline buffer at 37 degrees C, PDS sutures have lower tensile strength than PLLA sutures and the tensile strength of Vicryl was unmeasurable because of fragmentation. Initially, PLLA fibers disintegrated into fibrils during degradation triggering an inflammatory response comparable to degradable multifilament sutures. However, the intensity of the inflammatory response against the PLLA fibers decreased and after 80 weeks implantation in the muscle layer of the abdominal wall of rats it was comparable to the one against Ethilon. The inflammatory response against Ethilon, which is considered to be nondegradable, increased in the same period, probably due to the change in shape. In practice, the handling characteristics of PLLA sutures are superior to the monofilament sutures like PDS and Ethilon and comparable with the multifilament sutures like Vicryl and silk. The knot security of PLLA sutures are expected to be better than the knot security of the monofilament sutures, but this remains to be investigated. It is concluded that dry-spun/hot-drawn (reinforced) PLLA fibers have the potential for use as long-term degradable suture material.