Generalized Gauss maps and integrals for three-component links: toward higher helicities for magnetic fields and fluid flows, Part 2

We describe a new approach to triple linking invariants and integrals, aiming for a simpler, wider and more natural applicability to the search for higher order helicities of fluid flows and magnetic fields. To each three-component link in Euclidean 3-space, we associate a geometrically natural generalized Gauss map from the 3-torus to the 2-sphere, and show that the pairwise linking numbers and Milnor triple linking number that classify the link up to link homotopy correspond to the Pontryagin invariants that classify its generalized Gauss map up to homotopy. This can be viewed as a natural extension of the familiar fact that the linking number of a two-component link in 3-space is the degree of its associated Gauss map from the 2-torus to the 2-sphere. When the pairwise linking numbers are all zero, we give an integral formula for the triple linking number analogous to the Gauss integral for the pairwise linking numbers, but patterned after J.H.C. Whitehead's integral formula for the Hopf invariant. The integrand in this formula is geometrically natural in the sense that it is invariant under orientation-preserving rigid motions of 3-space, while the integral itself can be viewed as the helicity of a related vector field on the 3-torus. In the first paper of this series [math.GT 1101.3374] we did this for three-component links in the 3-sphere. Komendarczyk has applied this approach in special cases to derive a higher order helicity for magnetic fields whose ordinary helicity is zero, and to obtain from this nonzero lower bounds for the field energy.Comment: 22 pages, 8 figures. arXiv admin note: text overlap with arXiv:1101.337

Tierexperimentelle Validierung einer neuartigen, minimal-invasiven implantierbaren Trikuspidalklappenprothese

Erkrankungen der Trikuspidalklappe (TK) werden häufig beobachtet. Eine leichtgradige Trikuspidalklappeninsuffizienz (TI) wird in 80 % als Zufallsbefund bei asymptomatischen Patienten in der Echokardiographie festgestellt (Nath et al. 2004). Die häufigste Ursache einer TI ist eine sekundäre Insuffizienz wegen einer strukturellen Erkrankung der linken Herzklappen. Eine konventionelle Trikuspidalklappenoperation ist verbunden mit einer hohen perioperativen Morbidität und Letalität als isolierte Prozedur. Der Eingriff erfolgt oft als Reoperation, was das perioperative Risiko zusätzlich erhöht. Eine kathetergestützte Klappenchirurgie könnte vielen Patienten, die einer konventionellen Klappenoperation aufgrund des Risikos nicht zugänglich wären, eine therapeutische Behandlung ermöglichen. Im Vordergrund der Dissertationsarbeit steht die Frage nach der Machbarkeit und Sicherheit einer minimalinvasiven, katheterbasierten Implantation einer heterotopen Trikuspidalklappenprothese im tierexperimentellen Modell am Schaf. Die Prozedur wurde als transvenöse Implantation einer gefalteten Prothese unter Vollnarkose und Röntgen-Kontrolle am schlagenden Herz konzipiert. Zusätzlich wurde im Rahmen des Versuchs eine hochgradige TI durch ein periinterventionelles Verfahren erzeugt. Durch die experimentelle Studie konnte gezeigt werden, dass eine perkutane und interventionelle Implantation der kathetergestützten Trikuspidalklappenprothese möglich ist. Das etablierte Verfahren konnte erfolgreich an 7 Versuchstieren komplikationslos durchgeführt werden. In 6 (86 %) Fällen konnte die gewünschte Lage erreicht werden, in 1 (14 %) Fall wurde eine paravalvuläre Leckage bei kompetenter Klappenfunktion festgestellt. Iatrogene Verletzungen traten nicht auf, es wurden keine relevanten Rhythmusstörungen beobachtet. Langfristig dient der Tierversuch einer Entwicklung einer minimalinvasiven Therapie der TI durch Klappenersatz mit einer Stentprothese. Im Rahmen des Experiments konnte eine reproduzierbare Methode zur Implantation einer Trikuspidalklappenprothese durch transvenösen Zugang etabliert werden

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy

Species-specific and pathotype-specific binding of bacteria to zymogen granule membrane glycoprotein 2 (GP2)

With interest we read the paper by Juste et al 1 proposing the amount of zymogen-granule membrane glycoprotein 2 (GP2) on the surface of intestinal bacteria as a Crohn\u27s disease (CD) marker. Indeed, a decreased GP2 level was found on microbes in patients with CD as compared to those of healthy controls. GP2 is a homologue to the urinary Tamm–Horsefall protein demonstrating an antimicrobial function by binding type 1-fimbriated uropathogenic Escherichia coli (UPEC). Likewise, GP2 seems to interact with intestinal bacteria as a specific receptor of bacterial type-1 fimbriae (FimH) on intestinal microfold cells that are partaking in immune responses against such microbes.2 GP2 is overexpressed in the inflamed intestine of patients with CD and has an immunomodulating role in innate and acquired immune responses.3 ,4Interestingly, GP2 was identified as autoantigen of pancreatic antibodies in CD.4 Altogether, these findings indicate two major GP2 sources (pancreatic/intestinal) and support a role for GP2 in the interaction between the immune system and intestinal microbiota.3 Thus, loss of tolerance to GP2 could play a role in CD\u27s pathophysiology supposed to be exacerbated by preceding intestinal infections. In general, the findings by Juste et al 1 may be explained by a lower pancreatic GP2 secretion, an impaired GP2 binding to bacteria, or by a higher prevalence of bacteria with poor or no GP2 binding in patients with CD

BRCA1 Norway: comparison of classifcation for BRCA1 germline variants detected in families with suspected hereditary breast and ovarian cancer between different laboratories

Pathogenic germline variants in Breast cancer susceptibility gene 1 (BRCA1) predispose carriers to hereditary breast and ovarian cancer (HBOC). Through genetic testing of patients with suspected HBOC an increasing number of novel BRCA1 variants are discovered. This creates a growing need to determine the clinical significance of these variants through correct classification (class 1–5) according to established guidelines. Here we present a joint collection of all BRCA1 variants of class 2–5 detected in the four diagnostic genetic laboratories in Norway. The overall objective of the study was to generate an overview of all BRCA1 variants in Norway and unveil potential discrepancies in variant interpretation between the hospitals, serving as a quality control at the national level. For a subset of variants, we also assessed the change in classification over a ten-year period with increasing information available. In total, 463 unique BRCA1 variants were detected. Of the 126 variants found in more than one hospital, 70% were interpreted identically, while 30% were not. The differences in interpretation were mainly by one class (class 2/3 or 4/5), except for one larger discrepancy (class 3/5) which could affect the clinical management of patients. After a series of digital meetings between the participating laboratories to disclose the cause of disagreement for all conflicting variants, the discrepancy rate was reduced to 10%. This illustrates that variant interpretation needs to be updated regularly, and that data sharing and improved national inter-laboratory collaboration greatly improves the variant classification and hence increases the accuracy of cancer risk assessment.publishedVersio

Tightness in contact metric 3-manifolds

This paper begins the study of relations between Riemannian geometry and global properties of contact structures on 3-manifolds. In particular we prove an analog of the sphere theorem from Riemannian geometry in the setting of contact geometry. Specifically, if a given three dimensional contact manifold (M,\xi) admits a complete compatible Riemannian metric of positive 4/9-pinched curvature then the underlying contact structure \xi is tight; in particular, the contact structure pulled back to the universal cover is the standard contact structure on S^3. We also describe geometric conditions in dimension three for \xi to be universally tight in the nonpositive curvature setting.Comment: 29 pages. Added the sphere theorem, removed high dimensional material and an alternate approach to the three dimensional tightness radius estimate

Derangement of body representation in complex regional pain syndrome: report of a case treated with mirror and prisms

Perhaps the most intriguing disorders of body representation are those that are not due to primary disease of brain tissue. Strange and sometimes painful phantom limb sensations can result from loss of afference to the brain; and Complex Regional Pain Syndrome (CRPS)—the subject of the current report—can follow limb trauma without pathology of either the central or peripheral nervous system. This enigmatic and vexing condition follows relatively minor trauma, and can result in enduring misery and a useless limb. It manifests as severe pain, autonomic dysfunction, motor disability and ‘neglect-like’ symptoms with distorted body representation. For this special issue on body representation we describe the case of a patient suffering from CRPS, including symptoms suggesting a distorted representation of the affected limb. We report contrasting effects of mirror box therapy, as well as a new treatment—prism adaptation therapy—that provided sustained pain relief and reduced disability. The benefits were contingent upon adapting with the affected limb. Other novel observations suggest that: (1) pain may be a consequence, not the cause, of a disturbance of body representation that gives rise to the syndrome; (2) immobilisation, not pain, may precipitate this reorganisation of somatomotor circuits in susceptible individuals; and (3) limitation of voluntary movement is neither due to pain nor to weakness but, rather, to derangement of body representation which renders certain postures from the repertoire of hand movements inaccessible

PTEN as a Prognostic and Predictive Marker in Postoperative Radiotherapy for Squamous Cell Cancer of the Head and Neck

BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck

Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR® Yfiler® PCR amplification kit

The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR® Yfiler® polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730–1,764 DNA-confirmed father–son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son’s birth) of fathers with mutations was with 34.40 (±11.63) years higher than that of fathers without ones at 30.32 (±10.22) years, a difference that is highly statistically significant (p < 0.001). A Poisson-based modeling revealed that the Y-STR mutation rate increased with increasing father’s age on a statistically significant level (α = 0.0294, 2.5% quantile = 0.0001). From combining our data with those previously published, considering all together 135,212 meiotic events and 331 mutations, we conclude for the Yfiler Y-STRs that (1) none had a mutation rate of >1%, 12 had mutation rates of >0.1% and four of <0.1%, (2) single-repeat changes were strongly favored over multiple-repeat ones for all loci but 1 and (3) considerable variation existed among loci in the ratio of repeat gains versus losses. Our finding of three Y-STR mutations in one father–son pair (and two pairs with two mutations each) has consequences for determining the threshold of allelic differences to conclude exclusion constellations in future applications of Y-STRs in paternity testing and pedigree analyses