The role of MRI biomarkers in evaluation of symptomatic pineal cysts - a retrospective analysis.

BACKGROUND: Our aim was to determine whether the Apparent Diffusion Coefficient is able to predict the presence of a symptomatic pineal cyst by detecting cerebral edema. METHODS: We retrospectively analyzed MRIs of 45 patients with pineal cysts before and after resection and 51 patients without pineal cysts, comparing ADC values of thalamus, central, periventricular and subcortical white matter. Furthermore we evaluated cyst size and morphology and analyzed its correlation to ADC values in corresponding patients. RESULTS: Differences between patients with symptomatic pineal cyst and control group were not significant (p = 0.200 - 0.968). ADC ratios did not change significantly after resection of the cyst (p = 0.575 - 0.862). Cyst size showed no significant correlation to ADC ratios (p = 0.071 - 0.918). Raw data analyses revealed more significance, especially periventricularly and in central white matter, which resulted in significant interhemispheric differences in ADC ratios in both subgroups (p < 0.001 and p = 0.031). MRI of 1.5T showed consistently higher values than 3T but mostly insignificant. CONCLUSION: Our analysis revealed no evidence that pineal cysts lead to intracerebral edema caused by venous compression. Since variability was higher than the differences seen, ADC sequences do not appear to be an appropriate diagnostic tool for symptomatic pineal cysts.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Growth in stratospheric chlorine from short-lived chemicals not controlled by the Montreal Protocol.

We have developed a chemical mechanism describing the tropospheric degradation of chlorine containing very short-lived substances (VSLS). The scheme was included in a global atmospheric model and used to quantify the stratospheric injection of chlorine from anthropogenic VSLS ( ClyVSLS) between 2005 and 2013. By constraining the model with surface measurements of chloroform (CHCl3), dichloromethane (CH2Cl2), tetrachloroethene (C2Cl4), trichloroethene (C2HCl3), and 1,2-dichloroethane (CH2ClCH2Cl), we infer a 2013 ClyVSLS mixing ratio of 123 parts per trillion (ppt). Stratospheric injection of source gases dominates this supply, accounting for ∼83% of the total. The remainder comes from VSLS-derived organic products, phosgene (COCl2, 7%) and formyl chloride (CHClO, 2%), and also hydrogen chloride (HCl, 8%). Stratospheric ClyVSLS increased by ∼52% between 2005 and 2013, with a mean growth rate of 3.7 ppt Cl/yr. This increase is due to recent and ongoing growth in anthropogenic CH2Cl2-the most abundant chlorinated VSLS not controlled by the Montreal Protocol.

Development of a dynamic model for ventral hernia mesh repair.

INTRODUCTION: The adequate way of mesh fixation in laparoscopic ventral hernia repair is still subject to debate. So far, simulation has only been carried out in a static way, thereby omitting dynamic effects of coughing or vomiting. We developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS: An aluminium cylinder was equipped with a pressure controlled, fluid-filled plastic bag, simulating the abdominal viscera. A computer-controlled system allowed the control of influx and efflux, thus creating pressure peaks of up to 200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany). The model was controlled for the friction coefficient of the tissue against the mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS: The model was able to create pressure peaks equivalent to physiologic coughs or vomiting. Physiologic elasticity was thereby maintained. We could show that the friction coefficient is crucial to achieve a physiologic situation. The meshes showed a tendency to dislocate with an increasing number of coughs (Fig. 4). Nevertheless, when applied in a plain manner, the meshes withstood more cough cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS: The dynamic movement of the abdominal wall, the friction between tissue and mesh and the way of mesh application are crucial factors that have to be controlled for in simulation of ventral abdominal hernia closure. We could demonstrate that patient specific factors such as the frequency of coughing as well as the application technique influence the long term stability of the mesh.

A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1.

Juvenile nephronophthisis (NPH), an autosomal recessive cystic kidney disease, is the primary genetic cause of chronic renal failure in children. About two thirds of patients with NPH carry a large homozygous deletion at the gene locus NPH1 on 2q13. We here identify a novel gene. NPHP1, which extends over most of this common deletion. The 4.5-kb transcript encodes a protein with an SH3 domain, which is highly conserved throughout evolution. The 11-kb interval between the 3' end of NPHP1 and an inverted repeat containing the distal deletion breakpoint was found to contain the first exon of a second gene, MALL. In patients with a hemizygous deletion of the NPH1 region, additional point mutations were found in NPHP1 but not in MALL.

Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure.

Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosomal recessive salt-losing nephropathies. Identification of three genes that code for renal transporters and channels as responsible for aBS has resulted in new insights into renal salt handling, diuretic action and blood-pressure regulation. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deafness (SND) and renal failure, has been mapped to chromosome 1p. We report here the identification by positional cloning, in a region not covered by the human genome sequencing projects, of a new gene, BSND, as the cause of BSND. We examined ten families with BSND and detected seven different mutations in BSND that probably result in loss of function. In accordance with the phenotype, BSND is expressed in the thin limb and the thick ascending limb of the loop of Henle in the kidney and in the dark cells of the inner ear. The gene encodes a hitherto unknown protein with two putative transmembrane alpha-helices and thus might function as a regulator for ion-transport proteins involved in aBS, or else as a new transporter or channel itself.

[Patient participation in medical decision making within an integrated health care system in Germany: results of a controlled cohort study]. / Patientenbeteiligung bei medizinischen Entscheidungen in der Integrierten Versorgung Gesundes Kinzigtal: Ergebnisse einer kontrollierten Kohortenstudie.

An integrated health care project called "Gesundes Kinzigtal" was conducted in a rural area in Germany. As part of the project, physicians were trained and other measures were taken to enhance patient involvement in medical decision making. As part of the external evaluation, various effects regarding patient involvement in medical decision making, patient involvement and information preference, decision confidence, patient satisfaction with ambulatory care and patient quality of life were examined. The data were gathered by means of a questionnaire on an annual basis between 2007 and 2009. Effects were compared between patients who were participating in the integrated care project and two control groups. Analyses are based on the data of 1,205 patients. Over time all outcomes decreased slightly, except for information preference and physical quality of life. No statistically significant intervention effects on patient involvement in medical decision making or any other outcome variable could be found. The intensity of the training was presumably too low to establish an enduring change in the physician-patient interaction.

Standardized suturing can prevent slackening or bursting suture lines in midline abdominal incisions and defects.

PURPOSE: Incisional hernias often follow open abdominal surgery. A small-stitch-small-bite suture might close the incision durably. We analyzed specific details of this closure technique and assessed their influence on the closure stability. METHODS: The effects of cyclic loads, simulating coughs were investigated on a bench test. We prepared porcine bellies in the median line and bovine flanks parallel to the muscle fibers with 15 cm long incisions. Then we punched round or rhomboid defects with a diameter of 5-10 cm into the center of the incision. Monomax® 2-0 and Maxon® 1 and 2-0 were used as suture materials. We tested the durability of the closure with pressure impacts of 210 mmHg repeated 425 times. Throughout the experiments, we modified the suturing technique, the surgeon, the tissue tension, the defect size and shape and the suture diameter. RESULTS: Standardizing the suture technique improved the durability of the closure significantly. Any other variations showed minor influences after standardization. All incisions with round defects up to 7.5 cm width withstood 425 impacts using standardized suturing. Unstandardized sutures failed in all cases. When closing an incision with a 10 cm wide defect, the tissues ruptured frequently next to the suture line. We defined criteria to standardize this suturing technique. For the first time, we developed a suture factor related to the durability of a sutured tissue closure. We integrated the suture factor into the concept of biomechanically durable repairs. CONCLUSIONS: Suturing the abdominal wall with a standardized suturing technique improves its durability significantly.

Metastable CrMnNi steels processed by laser powder bed fusion: experimental assessment of elementary mechanisms contributing to microstructure, properties and residual stress.

The complex thermal history imposed by the laser-based powder bed fusion of metals (PBF-LB/M) process is known to promote the evolution of unique microstructures. In the present study, metastable CrMnNi steels with different nickel contents and, thus, different phase stabilities are manufactured by PBF-LB/M. Results clearly reveal that an adequate choice of materials will allow to tailor mechanical properties as well as residual stress states in the as-built material to eventually redundantize any thermal post-treatment. The chemical differences lead to different phase constitutions in as-built conditions and, thus, affect microstructure evolution and elementary deformation mechanisms upon deformation, i.e., twinning and martensitic transformation. Such alloys designed for additive manufacturing (AM) highlight the possibility to tackle well-known challenges in AM such as limited damage tolerance, porosity and detrimental residual stress states without conducting any post treatments, e.g., stress relieve and hot isostatic pressing. From the perspective of robust design of AM components, indeed it seems to be a very effective approach to adapt the material to the process characteristics of AM.

Biomechanics applied to incisional hernia repair - Considering the critical and the gained resistance towards impacts related to pressure.

BACKGROUND: Incisional hernia repair is burdened with recurrence, pain and disability. The repair is usually carried out with a textile mesh fixed between the layers of the abdominal wall. METHODS: We developed a bench test with low cyclic loading. The test uses dynamic intermittent strain resembling coughs. We applied preoperative computed tomography of the abdomen at rest and during Valsalva's maneuver to the individual patient to analyze tissue elasticity. FINDINGS: The mesh, its placements and overlap, the type and distribution of fixation elements, the elasticity of the tissue of the individual and the closure of the abdominal defect-all aspects influence the reconstruction necessary. Each influence can be attributed to a relative numerical quantity which can be summed up into a characterizing value. The elasticity of the tissues within the abdominal wall of the individual patient can be assessed with low-dose computed tomography of the abdomen with Valsalva's maneuver. We established a procedure to integrate the results into a surgical concept. We demonstrate potential computer algorithms using non-rigid b-spline registration and artificial intelligence to further improve the evaluation process. INTERPRETATION: The bench test yields relative values for the characterization of hernia, mesh and fixation. It can be applied to patient care using established procedures. The clinical application in the first ninety-six patients shows no recurrences and reduced pain levels after one year. The concept has been spread to other surgical groups with the same results in another fifty patients. Future efforts will make the abdominal wall reconstruction more predictable.

Correlated electron emission in multiphoton double ionization

Electronic correlations govern the dynamics of many phenomena in nature, such as chemical reactions and solid state effects, including superconductivity. Such correlation effects can be most clearly investigated in processes involving single atoms. In particular, the emission of two electrons from an atom--induced by the impact of a single photon, a charged particle or by a short laser pulse--has become the standard process for studies of dynamical electron correlations. Atoms and molecules exposed to laser fields that are comparable in intensity to the nuclear fields have extremely high probabilities for double ionization; this has been attributed to electron-electron interaction. Here we report a strong correlation between the magnitude and the direction of the momentum of two electrons that are emitted from an argon atom, driven by a femtosecond laser pulse (at 38 TW cm(-2)). Increasing the laser intensity causes the momentum correlation between the electrons to be lost, implying that a transition in the laser-atom coupling mechanism takes place.

Machine learning in infection management using routine electronic health records: tools, techniques, and reporting of future technologies.

BACKGROUND: Machine learning (ML) is increasingly being used in many areas of health care. Its use in infection management is catching up as identified in a recent review in this journal. We present here a complementary review to this work. OBJECTIVES: To support clinicians and researchers in navigating through the methodological aspects of ML approaches in the field of infection management. SOURCES: A Medline search was performed with the keywords artificial intelligence, machine learning, infection∗, and infectious disease∗ for the years 2014-2019. Studies using routinely available electronic hospital record data from an inpatient setting with a focus on bacterial and fungal infections were included. CONTENT: Fifty-two studies were included and divided into six groups based on their focus. These studies covered detection/prediction of sepsis (n = 19), hospital-acquired infections (n = 11), surgical site infections and other postoperative infections (n = 11), microbiological test results (n = 4), infections in general (n = 2), musculoskeletal infections (n = 2), and other topics (urinary tract infections, deep fungal infections, antimicrobial prescriptions; n = 1 each). In total, 35 different ML techniques were used. Logistic regression was applied in 18 studies followed by random forest, support vector machines, and artificial neural networks in 18, 12, and seven studies, respectively. Overall, the studies were very heterogeneous in their approach and their reporting. Detailed information on data handling and software code was often missing. Validation on new datasets and/or in other institutions was rarely done. Clinical studies on the impact of ML in infection management were lacking. IMPLICATIONS: Promising approaches for ML use in infectious diseases were identified. But building trust in these new technologies will require improved reporting. Explainability and interpretability of the models used were rarely addressed and should be further explored. Independent model validation and clinical studies evaluating the added value of ML approaches are needed.

Biomechanical comparison of polylactide-based versus titanium miniplates in mandible reconstruction in vitro.

OBJECTIVES: Evaluation of the mechanical integrity and reliability of polylactide-based miniplates for osseous free flap fixation at the mandible in an experimental study setup of a mandible reconstruction model. MATERIAL AND METHODS: 1.0mm titanium miniplates (group TI) (MatrixMandible, DePuy Synthes, Umkirch, Germany) and 1.5mm polylactide miniplates (group PL) (Inion CPS, Inion Oy, Tampere, Finland) were used to fix a polyurethane (PU) fibula segment to a PU mandible reconstruction model using monocortical non-locking screws. Mastication was simulated via unilateral cyclic dynamic loading at 1Hz with increasing loads (+ 0.15N/cycle, Bionix, MTS, USA). A 3D optical tracking system (Aramis, GOM, Braunschweig, Germany) was used to determine interosteotomy movements (IOM). RESULTS: IOM were higher in the polylactide group (distal: P=0.001, mesial: P=0.001). Differences in mean stiffness (titanium: 478±68N/mm; polylactide: 425±38N/mm, P=0.240) and mean force at a vertical displacement of 1.0mm (titanium: 201.6±87.1N; polylactide: 141.3±29.9N, P=0.159) were not significant. CONCLUSIONS: The results of this study suggest that polylactide-based miniplates provide reduced mechanical integrity and higher interosteotomy movements in comparison to titanium miniplates in vitro. Indications for clinical use of polylactide-based miniplates in mandible reconstruction have to be placed critically. Future studies will focus on clinical complications of polylactide-based plates in risk patients.

Increasing hernia size requires higher GRIP values for a biomechanically stable ventral hernia repair.

BACKGROUND: Increasing hernia sizes lead to higher recurrence rates after ventral hernia repair. A better grip might reduce the failure rates. MATERIAL AND METHODS: A biomechanical model delivering dynamic intermittent strain (DIS) was used to assess grip values at various hernia orifices. The model consists of a water-filled aluminium cylinder covered with tissues derived from pig bellies which are punched with a central defect varying in diameter. DIS was applied mimicking coughs lasting for up to 2 s with peak pressures between 180 and 220 mmHg and a plateau phase of 0.1 s. Ventral hernia repair was simulated with hernia meshes in the sublay position secured by tacks, glue or sutures as needed to achieve certain grip values. Grip was calculated taking into account the mesh: defect area ratio and the fixation strength. Data were assessed using non-parametric statistics. RESULTS: Using a mesh classified as highly stable upon DIS testing (DIS class A) a reduced overlap without fixation led to early slippage (p < 0.001). With the application of 16 fixation points, transmural sutures were better than tacks with Securestrap® being better than Absorbatack® (p < 0.001). Plotting the likelihood of a durable repair as a function of the calculated grip higher grip values were needed with increasing hernia diameter to achieve biomechanical stability. This is important for clinical work since the calculated grip values both from a registry and from published data tend to drop as hernia sizes increase indicating biomechanical instability. CONCLUSION: The experimental work reported here demonstrates for the first time that higher grip values should be reached when repairing larger ventral hernias.

Promoting abnormal grain growth in Fe-based shape memory alloys through compositional adjustments.

Iron-based shape memory alloys are promising candidates for large-scale structural applications due to their cost efficiency and the possibility of using conventional processing routes from the steel industry. However, recently developed alloy systems like Fe-Mn-Al-Ni suffer from low recoverability if the grains do not completely cover the sample cross-section. To overcome this issue, here we show that small amounts of titanium added to Fe-Mn-Al-Ni significantly enhance abnormal grain growth due to a considerable refinement of the subgrain sizes, whereas small amounts of chromium lead to a strong inhibition of abnormal grain growth. By tailoring and promoting abnormal grain growth it is possible to obtain very large single crystalline bars. We expect that the findings of the present study regarding the elementary mechanisms of abnormal grain growth and the role of chemical composition can be applied to tailor other alloy systems with similar microstructural features.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

OBJECTIVES: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. METHODS: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. RESULTS: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. CONCLUSIONS: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

An evaluation of the current radiative forcing benefit of the Montreal Protocol at the high-Alpine site Jungfraujoch.

A combination of reconstructed histories, long-term time series and recent quasi-continuous observations of non-CO2 greenhouse gases at the high-Alpine site Jungfraujoch is used to assess their current global radiative forcing budget and the influence of regulations due to the Montreal Protocol on Substances that Deplete the Ozone Layer in terms of climate change. Extrapolated atmospheric greenhouse gases trends from 1989 assuming a business-as-usual scenario, i.e. no Montreal Protocol restriction, are presented and compared to the observations. The largest differences between hypothetical business-as-usual mixing ratios and current atmospheric observations over the last 16 years were found for chlorinated species, in particular methyl chloroform (CH3CCl3) at 167 to 203 ppt and chlorofluorocarbon-12 (CFC-12) at 121 to 254 ppt. These prevented increases were used to estimate the effects of their restrictions on the radiative forcing budget. The net direct effect due to the Montreal Protocol regulations reduces global warming and offsets about 14 to 30% of the positive greenhouse effect related to the major greenhouse gases CO2, CH4, N2O and also SF6, and about 12 to 22% of the hypothetical current radiative forcing increase without Montreal Protocol restrictions. Thus, the Montreal Protocol succeeded not only in reducing the atmospheric chlorine content in the atmosphere but also dampened global warming. Nevertheless, the Montreal Protocol controlled species still add to global warming.

Localization of source regions of selected hydrofluorocarbons combining data collected at two European mountain stations.

Ground-based in situ measurements of hydrofluorocarbons HFC-125, HFC-134a, and HFC-152a, which are regulated under the Kyoto Protocol, are carried out at four European sites within the SOGE (System of Observation of Halogenated Greenhouse Gases in Europe) program. Concentrations measured at the high mountain stations of Jungfraujoch (Switzerland) and Mte Cimone (Italy) together with back-trajectory statistical analysis are used in order to identify potential source regions on a European scale. Combining concentration data recorded at the two sites allows to reduce one of the problem which is inherent to the back-trajectory approach, i.e. the localisation of "ghost" sources in the wake of real sources. In this way, a more reliable picture of the location of European potential source regions is given.

Observations of long-lived anthropogenic halocarbons at the high-Alpine site of Jungfraujoch (Switzerland) for assessment of trends and European sources.

Anthropogenic halocarbons, such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons (HFCs), bromocarbons (halons) and long-lived chlorinated solvents have been measured continuously at the high-Alpine site of Jungfraujoch (Switzerland) since January 2000. Chloro- and bromo-containing halocarbons are responsible for the stratospheric ozone depletion and will be globally banned from usage within the next years. With the exception of the stable CFC-12 (CF2 Cl2), all major CFCs and chlorinated solvents show a negative trend in recent years in their background concentrations at Jungfraujoch. HCFCs, as their first-generation substitute, are still increasing with a few percent per year. However, the frequency and the strength of HCFCs pollution events, which are caused by regional European emissions, are already declining. This can be seen as a sign of the impending ban of these gases within the next years in Europe. On the other hand, HFCs as the second-generation substitutes, are increasing with relative rates of at least 10% per year (e.g. almost 5 ppt per year for HFC-134a). An allocation of European sources was attempted by combining measured concentrations with trajectories of air masses reaching the Jungfraujoch during pollution events. Potential source regions could be detected in Italy, France, Spain and Germany.