Time-Delay Cosmography: Measuring the Hubble Constant and Other Cosmological Parameters with Strong Gravitational Lensing.

Multiply lensed images of a same source experience a relative time delay in the arrival of photons due to the path length difference and the different gravitational potentials the photons travel through. This effect can be used to measure absolute distances and the Hubble constant ( H 0 ) and is known as time-delay cosmography. The method is independent of the local distance ladder and early-universe physics and provides a precise and competitive measurement of H 0 . With upcoming observatories, time-delay cosmography can provide a 1% precision measurement of H 0 and can decisively shed light on the current reported 'Hubble tension'. This manuscript details the general methodology developed over the past decades in time-delay cosmography, discusses recent advances and results, and, foremost, provides a foundation and outlook for the next decade in providing accurate and ever more precise measurements with increased sample size and improved observational techniques.

Implications of bacterial mineralisation in aquatic ecosystem response models.

Widespread wastewater pollution is a major barrier to the sustainable management of freshwater and coastal marine ecosystems worldwide. Integrated multi-disciplinary studies are necessary to improve waterway management and protect ecosystem integrity. This study used the Generalised Likelihood Uncertainty Estimation (GLUE) methodology to link microbial community ecotoxicology laboratory data to a mechanistic aquatic ecosystem response model. The generic model provided good predictive skill for major water quality constituents, including heterotrophic bacteria dynamics (r2 = 0.91). The model was validated against observed data across a gradient of effluent concentrations from community whole effluent toxicity (WET) laboratory tests. GLUE analysis revealed that a combined likelihood measure increased confidence in the predictive capability of the model. This study highlights the importance of calibrating aquatic ecosystem response models with net growth rates (i.e., sum of the growth minus loss rate parameter terms) of biological functional groups. The final calibrated net growth rate value of heterotrophic bacteria determined using the GLUE analysis was selected to be 0.58, which was significantly greater than the average literature value of -0.15. This finding demonstrated that use of literature parameter values without a good understanding of the represented processes could create misleading outputs and result in unsatisfactory conclusions. Further, fixed bulk mineralisation rate literature values are typically higher than realistically required in aquatic ecosystem response models. This indicates that explicitly including bacterial mineralisation is crucial to represent microbial ecosystem functioning more accurately. Our study suggests that improved data collection and modelling efforts in real-world management applications are needed to better address nutrients released into the natural environment. Future studies should aim to better understand the sensitivity of aquatic ecosystem response models to bacterial mineralisation rates.

Wastewater effluents cause microbial community shifts and change trophic status.

Widespread wastewater pollution is one of the greatest challenges threatening the sustainable management of rivers globally. Understanding microbial responses to gradients in environmental stressors, such as wastewater pollution, is crucial to identify thresholds of community change and to develop management strategies that protect ecosystem integrity. This study used multiple lines of empirical evidence, including a novel combination of microbial ecotoxicology methods in the laboratory and field to link pressure-stressor-response relationships. Specifically, community-based whole effluent toxicity (WET) testing and environmental genomics were integrated to determine real-world community interactions, shifts and functional change in response to wastewater pollution. Here we show that wastewater effluents above moderate (>10%) concentrations caused consistent significant shifts in bacterial community structure and function. These thresholds of community shifts were also linked to changes in the trophic state of receiving waters in terms of nutrient concentrations. Differences in the community responses along the effluent concentration gradient were primarily driven by two globally relevant bacterial indicator taxa, namely Malikia spp. (Burkholderiales) and hgcI_clade (Frankiales). Species replacement occurred above moderate effluent concentrations with abundances of Malikia spp. increasing, while abundances of hgcI_clade decreased. The responses of Malikia spp. and hgcI_clade matched gene patterns associated with globally important nitrogen cycling pathways, such as denitrification and nitrogen fixation, which linked the core individual taxa to putative function and ecosystem processes, rarely achieved in previous studies. This study has identified potential indicators of change in trophic status and the functional consequences of wastewater pollution. These findings have immediate implications for both the management of environmental stressors and protection of aquatic ecosystems.

Breast-conserving surgery with intraoperative radiotherapy in recurrent breast cancer: the patient's perspective.

PURPOSE: When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy. METHODS: Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (n = 26) was treated with BCS + IORT; group 2 (n = 35) received a standard mastectomy; group 3 (n = 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria. RESULTS: Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction). CONCLUSION: For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.

A novel real-world ecotoxicological dataset of pelagic microbial community responses to wastewater.

Real-world observational datasets that record and quantify pressure-stressor-response linkages between effluent discharges and natural aquatic systems are rare. With global wastewater volumes increasing at unprecedented rates, it is urgent that the present dataset is available to provide the necessary information about microbial community structure and functioning. Field studies were performed at two time-points in the Austral summer. Single-species and microbial community whole effluent toxicity (WET) testing was performed at a complete range of effluent concentrations and two salinities, with accompanying environmental data to provide new insights into nutrient and organic matter cycling, and to identify ecotoxicological tipping points. The two salinity regimes were chosen to investigate future scenarios based on a predicted salinity increase at the study site, typical of coastal regions with rising sea levels globally. Flow cytometry, amplicon sequencing of 16S and 18S rRNA genes and micro-fluidic quantitative polymerase-chain reactions (MFQPCR) were used to determine chlorophyll-a and total bacterial cell numbers and size, as well as taxonomic and functional diversity of pelagic microbial communities. This strong pilot dataset could be replicated in other regions globally and would be of high value to scientists and engineers to support the next advances in microbial ecotoxicology, environmental biomonitoring and estuarine water quality modelling.

[Influence of probiotics on the establishment of a competitive flora, as well as on antibiotic use and performance parameters in pig breeding farms]. / Einfluss von Probiotika auf die Etablierung einer Konkurrenzflora sowie auf den Antibiotikaverbrauch und die Leistung in Schweinezuchtbetrieben.

INTRODUCTION: The aim of the present study was to investigate the effect of Probiotics in Progress (PIP) on the establishment of a competitive flora as well as on antibiotic use and losses of suckling piglets in pig breeding farms. The tested products were PIP AHC® and PIP AHS® produced by "Chrisal AG" in Lommel, Belgium. PIP`s are cleaning products containing Bacillus spores. According to the manufacturer's specifications, they are able to establish a steady non-pathogenic stable flora. In a field trial in 19 pig breeding farms, the use of PIP-products did not lead to any reduction of antibiotic use or improvement of fertility parameters, especially in relation to losses of suckling piglets. In addition, we compared the bacterial flora using PIP products with the flora under conventional management conditions in a farrowing pen by means of swab samples. The use of PIP-products did not lead to any significant effect on the pen flora. Only very few swab samples contained a majority of probiotic Bacillus spp.

INTRODUCTION: Le but de la présente étude était d'étudier l'effet de Probiotica in Progress (PIP) sur l'établissement d'une flore concurrente ainsi que son effet sur la consommation d'antibiotiques et sur les pertes chez les porcelets dans les porcheries d'élevage. On a utilisé pour ce faire les produits PIP AHC® et PIP AHS® de la maison "Chrisal SA" à Lommel en Belgique. Les PIP sont des produits de nettoyage auxquels ont été adjoints des spores de Bacillus et qui, selon les informations du fabriquant, conduisent à l'établissement d'une flore d'écurie apathogène stable. Dans le cadre d'un essai de terrain dans 19 porcheries d'élevage, l'utilisation des produits PIP n'a amené aucune réduction de la consommation d'antibiotiques et aucune amélioration des performances, en particulier en ce qui concerne les pertes au niveau des porcelets. En outre on a comparé dans une porcherie, sur la base d'échantillons d'essuyage, la flore bactérienne présente sous l'effet de PIP à celle recueillie avec un management usuel. L'utilisation des produits PIP n'a pas amené d'effet significatif ou d'influence sur la flore bactérienne. Ce n'est que dans quelques échantillons qu'il a été possible de constater une présence augmentée de Bacillus spp. probiotiques.

[Unexpected tumour of the distal esophagus]. / Unerwarteter, intraoperativer Befund im Bereiche des distalen Osophagus.

We report a patient with unexpected intraoperative diagnosis of a big leiomyoma of the distal esophagus found during laparoscopic repair of a typ III hiatal hernia complicated by Cameron ulcer and chronic anaemia. Laparoscopic transhiatal enucleation of the tumour was performed with closure of the myotomy, Nissen fundoplication, and crural repair. Briefly, the literature of leiomyoma of the esophagus is reviewed with special regard to different therapeutic strategies.

A new surgical concept for rectal replacement after low anterior resection: the transverse coloplasty pouch.

OBJECTIVE: To analyze the feasibility, safety, complication and death rates, and early functional results of the transverse coloplasty pouch procedure after low anterior rectal resection and total mesorectal excision. SUMMARY BACKGROUND DATA: The authors previously developed a novel neorectal reservoir, the transverse coloplasty pouch, in an animal model; they report the first clinical data of a prospective phase 1 study. METHODS: Forty-one patients underwent low anterior rectal resection with total mesorectal excision for rectal cancer (n = 37) or benign pathology (n = 4). The continuity was restored with a transverse coloplasty pouch anastomosis, and the colon was defunctionalized for 3 months. Patients were followed up at 2-month intervals for functional outcome. RESULTS: Intraoperative complications occurred in three patients (7%), none related to the transverse coloplasty pouch. There were no hospital deaths and the total complication rate was 27% (11/41); an anastomotic leakage rate of 7% was recorded. The stool frequency was 3.4 per 24 hours at 2 months follow-up and gradually decreased to 2.1 per 24 hours at 8 months. Stool dysfunctions such as stool urgency, fragmentation, and incontinence grade 1 and 2 were regularly observed until 6 months; the incidence significantly decreased thereafter. None of the patients had difficulties in pouch evacuation. CONCLUSIONS: The transverse coloplasty pouch is a small-volume reservoir that can safely be used for reconstruction after sphincter-preserving rectal resection. The early functional outcome is favorable and can be compared to other colonic reservoirs. The concept of reducing early dysfunction seen after straight coloanal anastomosis and avoiding long-term problems of pouch evacuation is supported by this study. Future trials will compare the transverse coloplasty pouch with other techniques of restorative resections of the rectum.

Integrin alpha(v)beta(3) expression in colon carcinoma correlates with survival.

Integrin alpha(v)beta(3) is expressed by newly formed blood vessels in diseased and neoplastic tissue and can therefore be used as a marker for angiogenesis. We investigated its expression on the vasculature of 40 colon carcinomas using the anti-alpha(v)beta(3)-specific monoclonal antibody LM609. The average relapse-free interval and overall survival in patients suffering from colon carcinomas with high vascular expression of alpha(v)beta(3) integrin was significantly reduced compared with that in patients with low alpha(v)beta(3) integrin expressing tumor vasculature. Moreover, the expression level of alpha(v)beta(3) integrin correlated with the presence of liver metastases. In conclusion, we propose vascular expression of alpha(v)beta(3) integrin as a prognostic indicator for colon carcinoma.

[Serological survey of Sarcoptes scabies var. suis infection using colostrum samples: preliminary results]. / Serologische Bestandesuntersuchung der Sarcoptes scabiei var. suis Infektion mit Kolostralmilchproben: vorläufige Resultate.

Pig mange was investigated serologically in colostral samples with ELISA using Chekit Sarcoptest. This test has already been using to investigate sera samples from swine in veterinary practice. A total of 684 sow colostral samples were collected from 24 mange free breeding units and 6 units with clinical manifestation of mange infestation. The specificity of the test was more than 99% and the mean seroprevalence 30% (range 6% to 100%). This simple method will allow in the future not only the rapid and certain diagnosis of pig mange but also the screening of pig breeding units after eradication of the disease.

Incidence of port site recurrence after laparoscopic cholecystectomy for preoperatively unsuspected gallbladder carcinoma.

BACKGROUND: We sought to determine the incidence of recurrence of carcinoma at the port site and the outcome of patients with such recurrences after exploratory laparoscopy/laparoscopic cholecystectomy for unsuspected gallbladder carcinoma and analyzed aspects of the laparoscopic procedure associated with recurrences at the port site. METHODS: Thirty-seven patients with preoperatively unknown adenocarcinoma of the gallbladder were analyzed. The patients were part of a large prospective study of the Swiss Association of Laparoscopic and Thoracoscopic Surgery including 10,925 patients undergoing laparoscopic cholecystectomy. RESULTS: Preoperatively undiagnosed adenocarcinoma of the gallbladder is rarely encountered in patients undergoing laparoscopic cholecystectomy (0.34%). The incidence of recurrence of carcinoma at the port site in these patients is 14% (5 of 37) and is similar whether the primary tumor is confined to the gallbladder (T1/T2) or locally advanced (T3/T4). The recurrences at the port site were diagnosed within 6 to 16 months (median 10 months) after the operation. Patients with an intraoperative perforation of the gallbladder had a higher incidence of recurrences at the port site (40%) than had patients without perforation (9%; P = .13). All patients with recurrences at the port site had distant metastases and all died of the disease 12 to 35 months (median 19 months) after cholecystectomy; all patients with such recurrences and stage T1/T2 tumors subsequently had peritoneal metastases. CONCLUSIONS: Patients with a preoperatively undiagnosed adenocarcinoma of the gallbladder undergoing laparoscopy or laparoscopic cholecystectomy have a high incidence of recurrences at the port site, and the incidence increases when a gallbladder perforation occurs during the operation. All patients with such recurrences died of the disease. The diagnosis of an isolated recurrence at the port site may therefore be an indicator of disseminated disease in most cases.

[Technique and results of laparoscopic rectum resection]. / Technick und Resultate der laparoskopischen Rektumexstirpation.

The general principles of oncologic operations for colorectal cancer are the same for both open and laparoscopic surgery. Isolation of the tumor by occlusion of the intestinal lumen, early blockage of venous outflow, complete resection of the lymph node bearing mesenterium, high ligation of the artery and prevention of tumor cell dissemination during extirpation of the specimen are the most important factors. We present our technique for laparoscopic abdominoperineal resection, which fulfills the above mentioned criteria. From June 1993 to October 1994 we operated on 19 patients (median age 68 [47-91] years; male/female ratio 10/9). Laparoscopic abdominoperineal resection of the rectum was palliative in 3 patients and curative in 16. Tumors were located 3 (1-8) cm from the anal verge. In 3 patients the operation was converted to open surgery. Intraoperative complications were encountered in 3 patients. Median operation time was 300 (200-400) minutes and postoperative morbidity 8/19 (42%) leading to reoperation in one patient. 30-day mortality was nil. Three patients died 5, 8, and 14 months postoperatively due to metastatic disease (all 3 after initial palliation). One patient had local recurrence and liver metastasis and died 14 months after operation. Another patient died from liver metastases. In one patient a single liver metastasis was successfully removed. 14 patients were tumor-free after a median follow-up of 10 (3-14) months. There was no implantation metastasis on a trocar site. Laparoscopic abdominoperineal resection of the rectum is feasible and the results are comparable with those of open surgery. Local recurrence rate and incidence of liver metastases are comparable with open surgery after this short follow-up. However, 5-year survival is needed to judge the oncological radicality of laparoscopic abdominoperineal resection of the rectum.

Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers.

We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers.

[Laparoscopic cholecystectomy as standard therapy in acute cholecystitis. A prospective study]. / Die laparoskopische Cholecystektomie als Standardtherapie bei der akuten Cholecystitis. Eine prospektive Studie.

Between November 1989 and May 1994 103 laparoscopic cholecystectomies were performed for acute cholecystitis. Conversion rate was 4.9%. Mortality was 0. Postoperative morbidity was 10.7% (6.8% local complications, 3.9% systemic complications). None of the complications lead to a reoperation, no injuries of the common bile duct occurred. These results compare favorably to randomized studies of open cholecystectomy and to published result of laparoscopic cholecystectomy for acute cholecystitis. Main determining factor for technical difficulty of the operation was the lapse of time between onset of symptoms and operation. This is expressed in statistically different mean operative times in patients with short (1-6 days) and long (7-14; 15-21 days) clinical history of acute cholecystitis. We therefore conclude that early surgery, in selected cases even emergency surgery is indicated and that in expert hands laparoscopic cholecystectomy can be the treatment of choice for acute cholecystitis.

The popliteus tendon and its fascicles at the popliteal hiatus: gross anatomy and functional arthroscopic evaluation with and without anterior cruciate ligament deficiency.

Gross anatomical dissection of the popliteus muscle, the popliteus tendon and its fascicles, and their relation to the lateral meniscus was carried out in 14 human adult cadaver knees. Videoarthroscopy through an anterolateral portal was then used to assess and document the functional integrity of the popliteus tendon and its fascicles forming the popliteal hiatus in vivo. A control group of cruciate ligament intact knees (n = 107) was compared with an anterior cruciate ligament (ACL)-deficient group (n = 68). The incidence of structural lesions of the popliteus system was 18.7% in the control knees, 95% in 40 acute ACL disruptions, and 85.7% in 28 chronic ACL-deficient knees. Functional arthroscopic evaluation of the popliteus tendon and its fascicles blending into the lateral meniscus was a valuable adjunct in assessing secondary posterolateral restraints in acute and chronic ACL-incompetent knees.