Computed tomographic imaging and surgical management of distal insertional avulsion fragments of the caudal cruciate ligament in four horses

Objective To describe cases with caudal cruciate ligament (CdCL) avulsion fragments diagnosed based on computed tomography (CT) examination and report on arthroscopic fragment removal. Animals Four Warmblood horses with hindlimb lameness and osseous fragments located in the caudal medial femorotibial joint (mFTJ). Study design Short case series. Methods CT and arthroscopic evaluation of the caudal mFTJ were performed. The caudal mFTJ and the insertion of the CdCL on the tibia were assessed and removal of the avulsion fragments was attempted in three horses using a cranial intercondylar approach. Results The fragment was not accessible via caudomedial approaches in one horse. A cranial intercondylar approach was used in three horses, allowing removal of the intra-articular fragment in two horses, and removal of two-thirds of the proximal fragment in the last horse. Acute, profuse, arterial bleeding occurred in this horse during surgery with transient postoperative soft tissue swelling. Comorbidities included medial femoral condyle cartilage defects (3), cranial cruciate ligament lesions (2), and medial collateral ligament lesions (2). Horses were followed up for 16 months (median, range 11–28 months), at which point all were back in ridden exercise; owners' satisfaction was good. Conclusion CT examination confirmed the diagnosis and allowed evaluation of the stifle joint for comorbidities. A cranial intercondylar arthroscopic approach facilitated the removal of CdCL insertional avulsion fragments, although not always complete. Clinical significance A cranial intercondylar approach can allow access to CdCL avulsion fragments, but complications and incomplete removal remain possible

Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy

Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). Methods The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA;2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. Results In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye

Supergravity at Colliders

We consider supersymmetric theories where the gravitino is the lightest superparticle (LSP). Assuming that the long-lived next-to-lightest superparticle (NSP) is a charged slepton, we investigate two complementary ways to prove the existence of supergravity in nature. The first is based on the NSP lifetime which in supergravity depends only on the Planck scale and the NSP and gravitino masses. With the gravitino mass inferred from kinematics, the measurement of the NSP lifetime will test an unequivocal prediction of supergravity. The second way makes use of the 3-body NSP decay. The angular and energy distributions and the polarizations of the final state photon and lepton carry the information on the spin of the gravitino and on its couplings to matter and radiation.Comment: 13 pages, 11 figures; v2: 3 references added, to appear in Physics Letters

Semiautomated SD-OCT Measurements of Corneal Sublayer Thickness in Normal and Post-SMILE Eyes

Purpose:To test the reliability of a novel algorithm for measuring corneal epithelial thickness (ET) and stromal thickness of normal eyes and post-small incision lenticule extraction (SMILE) corneas with spectral-domain optical coherence tomography.Methods:In this prospective observational study, a customized semiautomated software algorithm was developed and applied to measure corneal ET and stromal thickness along the horizontal corneal meridian. Measurements were performed by 2 examiners in a randomized fashion on a sample of 40 eyes with previous SMILE for treatment of myopia and a control group composed of 40 normal eyes. The intrauser repeatability and interuser reproducibility were analyzed by calculating typical indices including the coefficient of variation and intraclass correlation coefficient. Corneal sublayer thickness profiles were compared between normal and post-SMILE eyes.Results:In both groups, coefficients of variation were 3.2% or lower and intraclass correlation coefficients were 0.929 or higher indicating excellent reliability of the measurement method. Central ET was on an average 6 m greater in post-SMILE corneas (58.8 5.4 m) compared with normal eyes (52.8 +/- 4.0 m), with P < 0.01. Also, there was greater interindividual variability in ET in post-SMILE corneas and their horizontal epithelial profile seemed to show a lenticular appearance.Conclusions:Highly favorable indices of measurement reliability were achieved for this novel method of measuring corneal sublayer pachymetry not only in normal eyes but also in eyes with previous SMILE. The corneal ET profile was significantly altered in post-SMILE eyes compared with normal corneas

Matter Antimatter Asymmetry and Neutrino Properties

The cosmological baryon asymmetry can be explained as remnant of heavy Majorana neutrino decays in the early universe. We study this mechanism for two models of neutrino masses with a large \nu_\mu-\nu_\tau mixing angle which are based on the symmetries SU(5) x U(1)_F and SU(3)_c x SU(3)_L x SU(3)_R x U(1)_F, respectively. In both cases B-L is broken at the unification scale \Lambda_{GUT}. The models make different predictions for the baryogenesis temperature and the gravitino abundance.Comment: latex2e, 14 pages, 2 figures, Contribution to the Festschrift for L. B. Okun, to appear in a special issue of Physics Reports, eds. V. L. Telegdi and K. Winte

To-many or to-one? All-in-one! Efficient purely functional multi-maps with type-heterogeneous hash-tries

An immutable multi-map is a many-to-many map data structure with expected fast insert and lookup operations. This data structure is used for applications processing graphs or many-to-many relations as applied in compilers, runtimes of programming languages, or in static analysis of object-oriented systems. Collection data structures are assumed to carefully balance execution time of operations with memory consumption characteristics and need to scale gracefully from a few elements to multiple gigabytes at least. When processing larger in-memory data sets the overhead of the data structure encoding itself becomes a memory usage bottleneck, dominating the overall performance. In this paper we propose AXIOM, a novel hash-trie data structure that allows for a highly efficient and type-safe multi-map encoding by distinguishing inlined values of singleton sets from nested sets of multi-mappings

Inhibition of VCP preserves retinal structure and function in autosomal dominant retinal degeneration

Due to continuously high production rates of rhodopsin (RHO) and high metabolic activity, photoreceptor neurons are especially vulnerable to defects in proteostasis. A proline to histidine substitution at position 23 (P23H) leads to production of structurally misfolded RHO, causing the most common form of autosomal dominant Retinitis Pigmentosa (adRP) in North America. The AAA-ATPase valosin-containing protein (VCP) extracts misfolded proteins from the ER membrane for cytosolic degradation. Here, we provide the first evidence that inhibition of VCP activity rescues degenerating P23H rod cells and improves their functional properties in P23H transgenic rat and P23H knock-in mouse retinae, both in vitro and in vivo. This improvement correlates with the restoration of the physiological RHO localization to rod outer segments (OS) and properly-assembled OS disks. As a single intravitreal injection suffices to deliver a long-lasting benefit in vivo, we suggest VCP inhibition as a potential therapeutic strategy for adRP patients carrying mutations in the RHO gene

A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia

Unified origin of baryons and dark matter

We investigate the possibility that both the baryon asymmetry of the universe and the observed cold dark matter density are generated by decays of a heavy scalar field which dominates the universe before nucleosynthesis. Since baryons and cold dark matter have common origin, this mechanism yields a natural explanation of the similarity of the corresponding energy densities. The cosmological moduli and gravitino problems are avoided.Comment: 12 pages, one figure; v2: matches version published in PL

Deep learning improves pancreatic cancer diagnosis using RNA-based variants

For optimal pancreatic cancer treatment, early and accurate diagnosis is vital. Blood-derived biomarkers and genetic predispositions can contribute to early diagnosis, but they often have limited accuracy or applicability. Here, we seek to exploit the synergy between them by combining the biomarker CA19-9 with RNA-based variants. We use deep sequencing and deep learning to improve differentiating pancreatic cancer and chronic pancreatitis. We obtained samples of nucleated cells found in peripheral blood from 268 patients suffering from resectable, non-resectable pancreatic cancer, and chronic pancreatitis. We sequenced RNA with high coverage and obtained millions of variants. The high-quality variants served as input together with CA19-9 values to deep learning models. Our model achieved an area under the curve (AUC) of 96% in differentiating resectable cancer from pancreatitis using a test cohort. Moreover, we identified variants to estimate survival in resectable cancer. We show that the blood transcriptome harbours variants, which can substantially improve noninvasive clinical diagnosis