Mapping Out Phase Diagrams with Generative Classifiers.

One of the central tasks in many-body physics is the determination of phase diagrams. However, mapping out a phase diagram generally requires a great deal of human intuition and understanding. To automate this process, one can frame it as a classification task. Typically, classification problems are tackled using discriminative classifiers that explicitly model the probability of the labels for a given sample. Here we show that phase-classification problems are naturally suitable to be solved using generative classifiers based on probabilistic models of the measurement statistics underlying the physical system. Such a generative approach benefits from modeling concepts native to the realm of statistical and quantum physics, as well as recent advances in machine learning. This leads to a powerful framework for the autonomous determination of phase diagrams with little to no human supervision that we showcase in applications to classical equilibrium systems and quantum ground states.

IFTT in children and adolescents-single-center experience and systematic review of literature.

PURPOSE: Isolated fallopian tube torsion (IFTT) is defined by rotation of the fallopian tube around itself without involving the ipsilateral ovary. It is a rare cause of acute lower abdominal pain in (adolescent) girls, but is commonly overlooked. Due to its rarity, literature is still scarce. Currently there is no generally accepted management and treatment. METHODS: A retrospective analysis of all IFTT cases treated in our institution was performed. In addition, a systematic literature research on pediatric IFTT was carried out on Medline/ PubMed database according to PRISMA principles using predefined search terms and inclusion criteria. Patient characteristics regarding age, clinical symptoms, diagnostic methods, treatment, and follow-up were analyzed. RESULTS: Three of our patients and fifty-nine reports totaling one hundred seventy girls were included in the analysis. Mean age was 13.0 years. Left tube was slightly more often affected (52.9%). Abdominal pain was present in 99.4% of cases accompanied with nausea in 57.1%. In only 16.4%, correct preoperative diagnosis was made. Salpingectomy was the most common treatment in 111 (66.9%) cases, 55 (33.1%) patients were treated with detorsion of the tube (organ-sparing management). Girls with symptoms longer than 1 day had a significant higher rate of salpingectomy (95% CI, P = 0.0323). CONCLUSION: When IFTT is suspected, emergency laparoscopy should be performed to possibly preserve future reproductive potential. In case of detorsion and reinstated blood supply, organ-preserving management should be performed with simultaneous addressment of concomitant pathology if possible. Sufficient long-term follow-up must be assured to get significant results to introduce guidelines for children and adolescents.

Genome-wide identification of disease-causing copy number variations in 450 individuals with anorectal malformations.

Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2, LPP, and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Re-sequencing of candidate genes FOXF1, HSPA6, HAAO, and KYNU in 522 individuals with VATER/VACTERL, VACTER/VACTERL-like association, and isolated anorectal malformation.

BACKGROUND: The acronym VATER/VACTERL association describes the combination of at least three component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). Individuals presenting two CFs have been termed VATER/VACTERL-like. Recently, FOXF1, HSPA6, HAAO, KYNU, TRAP1, and ZIC3 have been proposed as candidate genes for VATER/VACTERL, VATER/VACTERL-like, and ARM. Re-sequencing studies identified disease-causing variants in TRAP1 and ZIC3, the contribution of other genes was not independently investigated. One affected variant carrier in FOXF1 was previously identified. Here we re-sequenced FOXF1, HSPA6, HAAO, and KYNU in 522 affected individuals. METHODS: Using molecular inversion probe (MIP) technology, re-sequencing was performed in 63 individuals with VATER/VACTERL association, 313 with VATER/VACTERL-like association, and 146 with ARM. All individuals were of European ethnicity. Variant filtering considered variants with a minor allele frequency (MAF) ≤0.01 for putative recessive disease-genes HSPA6, HAAO, and KYNU. For the putative dominant disease-gene FOXF1 we considered variants with a MAF ≤0.0001. In silico prediction tools were used for further prioritization. RESULTS: Only two variants in FOXF1 in two independently affected individuals [c.443G>T, p.(Cys148Phe); c.850T>C, p.(Tyr284His)] passed our filter criteria. One individual presented with ARM, the second presented with TE and C comprising atrial and ventricular septal defects. Sanger sequencing confirmed both variants but also their inheritance from the healthy mother. CONCLUSION: Our analysis suggests that FOXF1, HSPA6, HAAO and KYNU do not play a major role in the formation of VACTER/VACTERL phenotypes or ARM.

Risk Factors Influencing the Outcomes of Kidney Re-Transplantation.

BACKGROUND Our kidney transplant waitlist includes 20% re-transplantations (TX2). Knowing what to expect is a clinical obligation. MATERIAL AND METHODS We compared graft and patient survival of all 162 TX2 patients, transplanted 2000 to 2009, with 162 patients after first transplantation (TX1) matched for age, sex, living/non-living donation, and transplantation date. Patient follow-up was 10 years. RESULTS TX2 graft and patient survivals were inferior to TX1 (p<0.001 and p=0.047). TX2 patients had a longer cumulative dialysis vintage, more human leucocyte antigen (HLA) mismatches, more panel-reactive HLA antibodies, more often received induction therapy with rabbit-antithymocyte globulin (rATG), and had a lower body mass index (all p<0.05). Death from infection and graft failure by rejection was more frequent after TX2 (both p<0.05) but not after TX1. Multivariable Cox regression analysis revealed that both cohorts had graft failure and death risk associated with infection and cardiovascular disease, and graft failure by humoral rejection. However, only TX2 patients had an additional risk of graft failure with early inferior graft function and of patient death with ≥2 comorbidities. Moreover, Kaplan-Meier analysis showed that TX2 and not TX1 patients had a lower graft and patient survival associated with infection and with ≥2 comorbidities (all p<0.05). CONCLUSIONS Re-transplantation is associated with worse graft outcomes mainly because of immunologic and graft-quality reasons, although the high number of comorbidities and infection severities aside from cardiovascular disease drive mortality. The more frequent rATG induction of TX2 patients could promote infection by enhancing immunosuppression. By addressing comorbidities, outcomes could possibly be improved.

Increased Incidence of Perforated Appendicitis in Children During COVID-19 Pandemic in a Bavarian Multi-Center Study.

Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care. Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group. Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018-2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018-2019 (p = 0.0165, Fisher's exact test). Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.

Congenital Y-urethra - A diagnostic and therapeutic challenge.

BACKGROUND: For the Y-subtype of urethral duplications expression and nomenclature vary, as treatment recommendations do. OBJECTIVE: To raise awareness of the variety and variable terminology of Y-type duplication of the urethra, and to discuss the diagnostic work-up in light of options for or against surgical reconstruction. MATERIALS AND METHODS: Five patients with congenital Y-urethra were treated in four institutions within 15 years (2004-2019). While patients were managed in our respective institution with some exchange of experience, all available data were shared and evaluated for this review. RESULTS: The age at initial presentation was 1 day-6 months. In three patients the Y-urethra was found together with an anorectal malformation (ARM). With the focus on reconstruction rather than suprapubic diversion the orthotopic urethra was restored in the majority of patients using either single-step or staged approaches while the accessory urethral limb was incorporated. This was successful despite additional procedures aiming at ARM reconstruction. The patients void spontaneously and do control urine and bowels. One patient underwent kidney transplantation as a consequence of associated renal anomalies while reconstructive attempts regarding his urethral anomaly failed. In two patients, uncertainty in recognizing the pathology delayed a purposive treatment. DISCUSSION: For this rare anomaly the terminology in the literature merges and suggestions for the treatment differ. Success in four out five patients supports an approach which makes use of the accessory ventral track to restore the orthotopic urethra. Since some patients present as a neonatal emergency with concomitant problems such as ARM, a basic understanding of the variable pathology is required. CONCLUSION: The cases of Y-urethra reported herein demonstrate that correct allocation at the initial presentation or at least prior to first surgical steps will preserve the chance for physiologic micturition and urinary continence. Timing of surgery has to be done in the context of associated malformations and is not an emergency as long as proper bladder drainage is ensured. However, relocation of the accessory track requires several procedures bearing risks of complications short and long-term. This may be an argument to consider any therapeutic strategy against other options such as postponed treatment or permanent suprapubic diversion. Evidence-based guidelines are lacking.

Spectral Structure and Many-Body Dynamics of Ultracold Bosons in a Double-Well.

We examine the spectral structure and many-body dynamics of two and three repulsively interacting bosons trapped in a one-dimensional double-well, for variable barrier height, inter-particle interaction strength, and initial conditions. By exact diagonalization of the many-particle Hamiltonian, we specifically explore the dynamical behavior of the particles launched either at the single-particle ground state or saddle-point energy, in a time-independent potential. We complement these results by a characterization of the cross-over from diabatic to quasi-adiabatic evolution under finite-time switching of the potential barrier, via the associated time evolution of a single particle's von Neumann entropy. This is achieved with the help of the multiconfigurational time-dependent Hartree method for indistinguishable particles (MCTDH-X)-which also allows us to extrapolate our results for increasing particle numbers.

Acute urinary retention in children.

BACKGROUND: Acute urinary retention is a common emergency in adult patients, foremost in older men. In childhood urinary retention is a rare entity with only sparse literature on the etiology. OBJECTIVE: To assess the etiology and treatment of acute urinary retention in the pediatric population and assess age and sex distribution. STUDY DESIGN: A retrospective analysis of all patients admitted to our emergency department with acute urinary retention between 2005 and 2019 was performed. Exclusion criteria were newborns (because of physiologic postnatal oliguria) and postoperative urinary retention during the same hospital stay. RESULTS: 113 children with acute urinary retention (ICD: R33) meeting the above criteria were identified. 16 Patients were excluded because of incomplete medical charts. 97 children were included into the study (age 0.5-18.3 years, mean age 5.3 years). 89 patients had one episode, 8 patients two episodes. A peak around the third year of age was observed. Sex ratio showed a 2:1 male to female distribution. Most common etiology was balanoposthitis (15.5%) and acute constipation/fecal impaction (15.5%). Traumatic urinary retention was found in 11.4% of the cases. Urinary tract infection were found 7.2%. No underlying reason could be found in 12.4% (idiopathic urinary retention). Other causes included febrile non-urinary infection (8.2%), subvesical obstruction (4.1%), vulvovaginitis (3.1%) and urethritis (2.1%). In 50% of the cases of urinary retention under 1 year of age (2 out of 4) an underlying tumor (rhabdomyosarcoma, sacral teratoma) was identified. DISCUSSION: Age and sex distribution were similar to previously published series; however, this study shows a marked difference concerning the etiology: e. g. we identified a significantly higher proportion of functional disorders as a reason for acute urinary retention in childhood. It is hypothesized that this is partly because previously published studies originate from areas (USA, Israel, Iran) with different socio-demographic and cultural background. CONCLUSION: AUR in children is a rare condition with very heterogeneous causes. Although the majority of cases exhibit mild underlying conditions, serious reasons, such as malignant diseases especially in the first year of life, must be excluded. AUR relief without catheterization is a child-friendly approach in cases of mild inflammatory or functional disorders and can help to minimize traumatization.

SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

Treatment Strategies and Outcome of the Exstrophy-Epispadias Complex in Germany: Data From the German CURE-Net.

Introduction: To evaluate the impact of reconstructive strategies and post-operative management on short- and long-term surgical outcome and complications of classical bladder exstrophy (CBE) patients' comprehensive data of the multicenter German-wide Network for Congenital Uro-Rectal malformations (CURE-Net) were analyzed. Methods: Descriptive analyses were performed between 34 prospectively collected CBE patients born since 2009, median 3 months old [interquartile range (IQR), 2-4 months], and 113 cross-sectional patients, median 12 years old (IQR, 6-21 years). Results: The majority of included individuals were males (67%). Sixty-eight percent of the prospectively observed and 53% of the cross-sectional patients were reconstructed using a staged approach (p = 0.17). Although prospectively observed patients were operated on at a younger age, the post-operative management did not significantly change in the years before and after 2009. Solely, in prospectively observed patients, peridural catheters were used significantly more often (p = 0.017). Blood transfusions were significantly more frequent in males (p = 0.002). Only half of all CBE individuals underwent inguinal hernia repair. Cross-sectional patients after single-stage reconstructions showed more direct post-operative complications such as upper urinary tract dilatations (p = 0.0021) or urinary tract infections (p = 0.023), but not more frequent renal function impairment compared to patients after the staged approach (p = 0.42). Continence outcomes were not significantly different between the concepts (p = 0.51). Self-reported continence data showed that the majority of the included CBE patients was intermittent or continuous incontinent. Furthermore, subsequent consecutive augmentations and catheterizable stomata did not significantly differ between the two operative approaches. Urinary diversions were only reported after the staged concept. Conclusions: In this German multicenter study, a trend toward the staged concept was observed. While single-stage approaches tended to have initially more complications such as renal dilatation or urinary tract infections, additional surgery such as augmentations and stomata appeared to be similar after staged and single-stage reconstructions in the long term.

[Primary obstructive megaureter: a domain of conservative treatment]. / Der Primär Obstruktive Megaureter (POM) ­ Eine Domäne konservativer Therapie.

The term "megaureter" is an entirely descriptive designation for a number of different entities. It is crucial to distinguish between primary and secondary forms of megaureter and between obstructive and/or refluxive forms. In the majority of cases, there is a primary obstruction in the terminal ureterovesical segment. The treatment of primary obstructive megaureter has changed fundamentally over the last 3 decades. Whereas ureteral reimplantation was the treatment of choice in the past, conservative treatment is now preferred in 85 to 90 % of patients. With the advent of endoscopic balloon dilatation, a modern, minimally-invasive treatment option has become an alternative to ureteral reimplantation in selected patients. However, due to the possibility of postoperative VUR (vesicoureteral reflux), it is necessary to emphasize that this option should not weaken the generally strict indication for surgical treatment of primary obstructive megaureter.

Vector field divergence of predictive model output as indication of phase transitions.

We introduce an alternative method to identify phase boundaries in physical systems. It is based on training a predictive model such as a neural network to infer a physical system's parameters from its state. The deviation of the inferred parameters from the underlying correct parameters will be most susceptible and diverge maximally in the vicinity of phase boundaries. Therefore, peaks in the vector field divergence of the model's predictions are used as indication of phase transitions. Our method is applicable for phase diagrams of arbitrary parameter dimension and without prior information about the phases. Application to both the two-dimensional Ising model and the dissipative Kuramoto-Hopf model show promising results.

Controlling photon antibunching from 1D emitters using optical antennas.

Single-photon emission is a hallmark of atom-like 0D quantum emitters, such as luminescent semiconductor nanocrystals, nitrogen vacancies in diamond and organic dye molecules. In higher dimensional nanostructures, on the other hand, multiple spatially separated electronic excitations may exist giving rise to more than one emitted photon at a time. We show that optical nanoantennas can be used to control the photon emission statistic of 1D nanostructures and to convert them into single-photon sources. Antenna-control exploits spatially confined near-field enhanced absorption and emission rates resulting in locally increased annihilation of mobile excitons and radiative recombination. As proof of concept, we experimentally demonstrate the improvement of the degree of antibunching in the photoluminescence of single carbon nanotubes using a metal tip at room temperature. Our results indicate that, in addition to improving the performance of single photon sources, optical antennas have the potential to open up a broad range of materials for quantum information technology.

Anterior Rectus Sheath Autograft in WRAP-Augmentation of Achilles Tendon Rupture.

Achilles tendon ruptures can be counted as the most common traumatic ankle injuries. As such, there is a comparatively large set of treatment options including surgical and nonsurgical approaches. The purpose of this case report is to demonstrate a new technique for a specific subgroup of Achilles tendon ruptures that present with a large tendinous gap. We used a 2-step procedure designed to grant additional stability through an autograft from the anterior rectus sheath of the patient. Two patients were treated after suffering traumatic Achilles tendon ruptures on the left side with a gap of >3.5 cm and a high demand in daily activities. The reconstruction was performed using an upper quadrant recuts sheath as a WRAP-augmentation. After securing the transplant tissue, the abdominal wall was reconstructed using a Vicryl™-Prolene™ mesh (VYPRO®, Johnson & Johnson Medical GmbH, Ethicon Deutschland, Norderstedt, Germany). After, a standard approach to the Achilles tendon was performed with a Kirchmayr-Kessler suture. The end result was then stabilized with a rectus sheath WRAP over a length of 14 to 15 cm. On the cases reported here, multiple clinical follow-ups were performed over a 5-year period. We can report highly satisfying results, with a return to sports activity after 6 months and no complications. As such we believe the rectus sheath autograft an effective solution for Achilles tendon ruptures with large gaps in healthy patients that demonstrate a high demand in daily activities.

Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin Grafts.

IMPACT STATEMENT: The search for an ideal "off-the-shelf" biomaterial for augmentation cystoplasty remains elusive and current scaffold configurations are hampered by mechanical and biocompatibility restrictions. In addition, preclinical evaluations of potential scaffold designs for bladder repair are limited by the lack of tractable large animal models of obstructive bladder disease that can mimic clinical pathology. The results of this study describe a novel, minimally invasive, porcine model of partial bladder outlet obstruction that simulates clinically relevant phenotypes. Utilizing this model, we demonstrate that acellular, bi-layer silk fibroin grafts can support the formation of vascularized, innervated bladder tissues with functional properties.

An aggressive form of Haemophilus parainfluenzae infective endocarditis presenting with limb weakness.

We present the case of a 49-year-old man with a bicuspid aortic valve who presented to the emergency department with limb weakness and a fever. Blood tests revealed a fulminant septic process with Haemophilus parainfluenzae bacteraemia, anaemia and thrombocytopenia. Imaging revealed a cervical spinal abscess and discitis causing spinal cord compression, in addition to multiple cerebral septic emboli, pleural effusions and ascites. A transoesophageal echocardiogram (TOE) performed post decompression of his spinal collection showed native aortic valve endocarditis with an associated large aortic root abscess. He underwent successful aortic valve surgery and a 6-week course of antibiotic therapy and made an excellent clinical recovery with no long-term complications from his condition.