Accelerating ILP solvers for Minimum Flow Decompositions through search space and dimensionality reductions

Given a flow network, the Minimum Flow Decomposition (MFD) problem is finding the smallest possible set of weighted paths whose superposition equals the flow. It is a classical, strongly NP-hard problem that is proven to be useful in RNA transcript assembly and applications outside of Bioinformatics. We improve an existing ILP (Integer Linear Programming) model by Dias et al. [RECOMB 2022] for DAGs by decreasing the solver's search space using solution safety and several other optimizations. This results in a significant speedup compared to the original ILP, of up to 55-90x on average on the hardest instances. Moreover, we show that our optimizations apply also to MFD problem variants, resulting in similar speedups, going up to 123x on the hardest instances. We also developed an ILP model of reduced dimensionality for an MFD variant in which the solution path weights are restricted to a given set. This model can find an optimal MFD solution for most instances, and overall, its accuracy significantly outperforms that of previous greedy algorithms while being up to an order of magnitude faster than our optimized ILP

Atypical Phimosis Secondary to a Preputial Metastasis from Rectal Carcinoma

Background: Cutaneous metastases from colorectal cancer are uncommon, accounting for 6.5% of all secondary skin lesions. They occur in advanced disease. The most common site is the abdomen. The penis is a rare site. Case Report: We report the case of a 79-year-old patient who presented, two years after rectocolectomy for a rectal adenocarcinoma, obstructive renal failure secondary to a presacral recurrence, as well as symptomatic phimosis associated with papulonodules invading the penis, scrotum and pubis. After hemodialysis, percutaneous pyelostomy, and double-J catheter placement, the patient underwent circumcision and a pubic skin biopsy. On histology and immunohistochemistry, a cutaneous metastasis originating from the rectal adenocarcinoma was diagnosed. Conclusions: Penile invasion by colorectal cancer revealed by phimosis is a rare occurrence but needs to be recognized and promptly diagnosed by biopsy in order to propose appropriate adjuvant therapy. These rare lesions can occur without any liver or lung involvement

Consultation on kidney stones, Copenhagen 2019 : lithotripsy in percutaneous nephrolithotomy

Purpose: To evaluate the balance between existing evidence and expert opinions on the safety and efficacy of new technological improvements in lithotripsy techniques for percutaneous nephrolithotomy (PCNL). Methods: A scoping review approach was applied to search literature in Pubmed, Embase, and Web of Science. Consensus by key opinion leaders was reached at a 2-day meeting entitled \u201cConsultation on Kidney Stones: Aspects of Intracorporeal Lithotripsy\u201d held in Copenhagen, Denmark, in September 2019. Results: New-generation dual-mode single-probe lithotripsy devices have shown favourable results compared with use of ballistic or ultrasonic lithotripters only. However, ballistic and ultrasonic lithotripters are also highly effective and safe and have been the backbone of PCNL for many years. Compared with standard PCNL, it seems that mini PCNL is associated with fewer bleeding complications and shorter hospital admissions, but also with longer operating room (OR) time and higher intrarenal pressure. Use of laser lithotripsy combined with suction in mini PCNL is a promising alternative that may improve such PCNL by shortening OR times. Furthermore, supine PCNL is a good alternative, especially in cases with complex renal stones and large proximal ureteric stones; in addition, it facilitates endoscopic combined intrarenal surgery (ECIRS). Conclusion: Recent technological improvements in PCNL techniques are promising, but there is a lack of high-level evidence on safety and efficacy. Different techniques suit different types of stones and patients. The evolution of diverse methods has given urologists the possibility of a personalized stone approach, in other words, the right approach for the right patient

Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk

Linear stability of the flow of a second order fluid past a wedge

The linear stability analysis of Rivlin–Ericksen fluids of second order is investigated for boundary layer flows, where a semi-infinite wedge is placed symmetrically with respect to the flow direction. Second order fluids belong to a larger family of fluids called order fluids, which is one of the first classes proposed to model departures from Newtonian behavior. Second order fluids can model non-zero normal stress differences, which is an essential feature of viscoelastic fluids. The linear stability properties are studied for both signs of the elasticity number K, which characterizes the non-Newtonian response of the fluid. Stabilization is observed for the temporal and spatial evolution of two-dimensional disturbances when K > 0 in terms of increase of critical Reynolds numbers and reduction of growth rates, whereas the flow is less stable when K 0 and diminished when K < 0

Characterization of prion disease associated with a two-octapeptide repeat insertion

Genetic prion disease accounts for 10–15% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt–Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt–Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt–Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt–Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Otalgia and eschar in the external auditory canal in scrub typhus complicated by acute respiratory distress syndrome and multiple organ failure

<p>Abstract</p> <p>Background</p> <p>Scrub typhus, a mite-transmitted zoonosis caused by <it>Orientia tsutsugamushi</it>, is an endemic disease in Taiwan and may be potentially fatal if diagnosis is delayed.</p> <p>Case presentations</p> <p>We encountered a 23-year-old previously healthy Taiwanese male soldier presenting with the right ear pain after training in the jungle and an eleven-day history of intermittent high fever up to 39°C. Amoxicillin/clavulanate was prescribed for otitis media at a local clinic. Skin rash over whole body and abdominal cramping pain with watery diarrhea appeared on the sixth day of fever. He was referred due to progressive dyspnea and cough for 4 days prior to admission in our institution. On physical examination, there were cardiopulmonary distress, icteric sclera, an eschar in the right external auditory canal and bilateral basal rales. Laboratory evaluation revealed thrombocytopenia, elevation of liver function and acute renal failure. Chest x-ray revealed bilateral diffuse infiltration. Doxycycline was prescribed for scrub typhus with acute respiratory distress syndrome and multiple organ failure. Fever subsided dramatically the next day and he was discharged on day 7 with oral tetracycline for 7 days.</p> <p>Conclusion</p> <p>Scrub typhus should be considered in acutely febrile patients with multiple organ involvement, particularly if there is an eschar or a history of environmental exposure in endemic areas. Rapid and accurate diagnosis, timely administration of antibiotics and intensive supportive care are necessary to decrease mortality of serious complications of scrub typhus.</p

Properties of flat-spectrum radio-loud narrow-line Seyfert 1 galaxies

Publisher's version/PDFWe have conducted a multiwavelength survey of 42 radio loud narrow-line Seyfert 1 galaxies (RLNLS1s), selected by searching among all the known sources of this type and omitting those with steep radio spectra. We analyse data from radio frequencies to X-rays, and supplement these with information available from online catalogues and the literature in order to cover the full electromagnetic spectrum. This is the largest known multiwavelength survey for this type of source. We detected 90% of the sources in X-rays and found 17% at [gamma] rays. Extreme variability at high energies was also found, down to timescales as short as hours. In some sources, dramatic spectral and flux changes suggest interplay between a relativistic jet and the accretion disk. The estimated masses of the central black holes are in the range ∼10[superscript 6−8] M[subscript circled dot], lower than those of blazars, while the accretion luminosities span a range from ∼0.01 to ∼0.49 times the Eddington limit, with an outlier at 0.003, similar to those of quasars. The distribution of the calculated jet power spans a range from ∼10[superscript 42.6] to ∼10[superscript 45.6] erg s[superscript −1], generally lower than quasars and BL Lac objects, but partially overlapping with the latter. Once normalised by the mass of the central black holes, the jet power of the three types of active galactic nuclei are consistent with each other, indicating that the jets are similar and the observational differences are due to scaling factors. Despite the observational differences, the central engine of RLNLS1s is apparently quite similar to that of blazars. The historical difficulties in finding radio-loud narrow-line Seyfert 1 galaxies might be due to their low power and to intermittent jet activity