A semi-automated quantum-mechanical workflow for the generation of molecular monolayers and aggregates.

Organic electronics (OE) such as organic light-emitting diodes or organic solar cells represent an important and innovative research area to achieve global goals like environmentally friendly energy production. To accelerate OE material discovery, various computational methods are employed. For the initial generation of structures, a molecular cluster approach is employed. Here, we present a semi-automated workflow for the generation of monolayers and aggregates using the GFNn-xTB methods and composite density functional theory (DFT-3c). Furthermore, we present the novel D11A8MERO dye interaction energy benchmark with high-level coupled cluster reference interaction energies for the assessment of efficient quantum chemical and force-field methods. GFN2-xTB performs similar to low-cost DFT, reaching DFT/mGGA accuracy at two orders of magnitude lower computational cost. As an example application, we investigate the influence of the dye aggregate size on the optical and electrical properties and show that at least four molecules in a cluster model are needed for a qualitatively reasonable description.

Efficient calculation of electronic coupling integrals with the dimer projection method via a density matrix tight-binding potential.

Designing organic semiconductors for practical applications in organic solar cells, organic field-effect transistors, and organic light-emitting diodes requires understanding charge transfer mechanisms across different length and time scales. The underlying electron transfer mechanisms can be efficiently explored using semiempirical quantum mechanical (SQM) methods. The dimer projection (DIPRO) method combined with the recently introduced non-self-consistent density matrix tight-binding potential (PTB) [Grimme et al., J. Chem. Phys. 158, 124111 (2023)] is used in this study to evaluate charge transfer integrals important for understanding charge transport mechanisms. PTB, parameterized for the entire Periodic Table up to Z = 86, incorporates approximate non-local exchange, allowing for efficient and accurate calculations for large hetero-organic compounds. Benchmarking against established databases, such as Blumberger's HAB sets, or our newly introduced JAB69 set and comparing with high-level reference data from ωB97X-D4 calculations confirm that DIPRO@PTB consistently performs well among the tested SQM approaches for calculating coupling integrals. DIPRO@PTB yields reasonably accurate results at low computational cost, making it suitable for screening purposes and applications to large systems, such as metal-organic frameworks and cyanine-based molecular aggregates further discussed in this work.

Intracorporeal or extracorporeal anastomosis after minimally invasive right colectomy: a systematic review and meta-analysis.

PURPOSE: As part of the wide adoption of minimally invasive surgery, intracorporeal anastomosis is becoming increasingly common. The benefits of minimally invasive versus open right colectomy are well known although the additional benefits of an intracorporeal anastomosis, performed laparoscopically or robotically, are unclear. The aim of this study was to assess the current literature comparing intracorporeal and extracorporeal anastomosis in the setting of laparoscopic and robotic-assisted right colectomy. METHODS: A systematic review and meta-analysis was conducted according to PRISMA and AMSTAR methods. Studies included were randomized controlled trials and prospective or retrospective cohort studies, between January 1 2010 and July 1 2021, comparing intracorporeal and extracorporeal anastomosis with laparoscopic and robotic approaches. Four groups were identified: laparoscopic extracorporeal anastomosis (L-ECA), laparoscopic intracorporeal anastomosis (L-ICA), robotic extracorporeal anastomosis (R-ECA), and robotic intracorporeal anastomosis (R-ICA). Operative time, rate of conversion to an open procedure, surgical site infection, reoperation within 30 days, postoperative complications within 30 days, and length of hospital stay were assessed. RESULTS: Twenty-one retrospective cohort studies were included in the final analysis. R-ICA and R-ECA had comparable operative times, but a robotic approach required more time than laparoscopic (68 min longer, p < 0.00001). Conversion to open surgery was 55% less likely in the R-ICA group vs. L-ICA, and up to 94% less likely in the R-ICA group in comparison to the R-ECA group. Length of hospital stay was shorter for R-ICA by a half day vs. R-ECA, and up to 1 day less vs. L-ECA. There were no differences in postoperative complications, reoperations, or surgical site infections, regardless of approach. However, the included studies all had high risks of bias due to confounding variables and patient selection. CONCLUSION: Robotic-assisted right colectomy with intracorporeal anastomosis was associated with shorter length of hospitalization and decreased rate of conversion to open surgery, compared to either laparoscopic or extracorporeal robotic approaches. Prospective studies are needed to better understand the true impact of robotic approach and intracorporeal anastomosis in right colectomy.

Evaluation of early clinical failure criteria for gram-negative bloodstream infections.

OBJECTIVES: The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI). METHODS: Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset). RESULTS: Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2-2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1-2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4-3.3), altered mental status (aOR 4.5, 95% CI 2.8-7.1), and white blood cell count >12 000/mm3 (aOR 2.7, 95% CI 1.8-4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively). CONCLUSIONS: Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure.

Achieving molecular orientation in thermally extruded 3D printed objects.

Three-dimensional (3D) printing is used to fabricate tissue scaffolds. Polymer chains in these objects are typically unoriented. The mechanical properties of these scaffolds can be significantly enhanced by proper alignment of polymer chains. However, post-processing routes to increase orientation can be limited by the geometry of the printed object. Here, we show that it is possible to orient polymer chains during printing by optimizing printing parameters to take advantage of the flow characteristics of the polymer. This is demonstrated by printing a polymeric scaffold for meniscus regeneration using poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate), poly(DTD DD). Alignment of polymer chains was achieved by translating the printhead at sufficiently high speeds when the polymer was still in a semi-solid state as it cooled from the fluid state at the tip of the nozzle using a critical combination of nozzle diameter, extrusion pressure, and temperature. The degree of orientation as evaluated by x-ray diffraction and thermal shrinkage, was greater than that of drawn fibers. Significant orientation and defect-free printing was achieved even for scaffolds with complex geometries. The ability to orient polymers during 3D printing has the potential to combine the advantages of 3D printing with the superior mechanical performance of more conventional polymer processing methods, such as drawing.

A Standardized Approach to Cesarean Surgical Technique and Its Effect on Operative Time and Surgical Morbidity.

OBJECTIVE: To evaluate the impact of a standardized surgical technique for primary cesarean deliveries (CDs) on operative time and surgical morbidity. MATERIALS AND METHODS: Two-year retrospective chart review of primary CD performed around the implementation of a standardized CD surgical technique. The primary outcome was total operative time (TOT). Secondary outcomes included incision-to-delivery time (ITDT), surgical site infection, blood loss, and maternal and fetal injuries. RESULTS: When comparing pre- versus postimplementation surgical times, there was no significant difference in TOT (76.5 vs. 75.9 minutes, respectively; p = 0.42) or ITDT (9.8 vs. 8.8 minutes, respectively; p = 0.06) when the entire cohort was analyzed. Subgroup analysis of CD performed early versus late in an academic year among the pre- and postimplementation groups showed no significant difference in TOT (79.3 early vs. 73.8 minutes late; p = 0.10) or ITDT (10.8 early vs. 8.8 minutes late; p = 0.06) within the preimplementation group. In the postimplementation group, however, there was significant decrease in TOT (80.5 early vs. 71.3 minutes late; p = 0.02) and ITDT (10.6 early vs. 6.8 minutes late; p < 0.01). Secondary outcomes were similar for both groups. CONCLUSION: A standardized surgical technique combined with surgical experience can decrease TOT and ITDT in primary CD without increasing maternal morbidity.

Endothelial cells on an aged subendothelial matrix display heterogeneous strain profiles in silico.

Within the artery intima, endothelial cells respond to mechanical cues and changes in subendothelial matrix stiffness. Recently, we found that the aging subendothelial matrix stiffens heterogeneously and that stiffness heterogeneities are present on the scale of one cell length. However, the impacts of these complex mechanical micro-heterogeneities on endothelial cells have not been fully understood. Here, we simulate the effects of matrices that mimic young and aged vessels on single- and multi-cell endothelial cell models and examine the resulting cell basal strain profiles. Although there are limitations to the model which prohibit the prediction of intracellular strain distributions in alive cells, this model does introduce mechanical complexities to the subendothelial matrix material. More heterogeneous basal strain distributions are present in the single- and multi-cell models on the matrix mimicking an aged artery over those exhibited on the young artery. Overall, our data indicate that increased heterogeneous strain profiles in endothelial cells are displayed in silico when there is an increased presence of microscale arterial mechanical heterogeneities in the matrix.

Pregnancy after endometrial ablation: a systematic review.

BACKGROUND: Pregnancies have been reported after endometrial ablation but there is little data regarding subsequent pregnancy outcomes. OBJECTIVE: To review systematically the available evidence regarding pregnancy outcomes after endometrial ablation, in order to equip physicians effectively to counsel women considering endometrial ablation. SEARCH STRATEGY: MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched through January 2017. SELECTION CRITERIA: Published and unpublished literature in any language describing pregnancy after endometrial ablation or resection was eligible. DATA COLLECTION AND ANALYSIS: Data about preconception characteristics and pregnancy outcomes were extracted and analysed according to study design of source and pregnancy viability. MAIN RESULTS: We identified 274 pregnancies from 99 sources; 78 sources were case reports. Women aged 26-50 years (mean 37.5 ± 5 years) conceived a median of 1.5 years after ablation (range: 3 weeks prior to 13 years after). When reported, 80-90% had not used contraception. In all, 85% of pregnancies from trial/observational studies ended in termination, miscarriage or ectopic pregnancy. Pregnancies that continued (case report and non-case report sources) had high rates of preterm delivery, caesarean delivery, caesarean hysterectomy, and morbidly adherent placenta. Case reports also frequently described preterm premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, uterine rupture, and neonatal demise. CONCLUSIONS: An unexpectedly high rate of pregnancy complications is reported in the available literature (which may reflect publication bias) and high-quality evidence is lacking. However, based on the existing evidence, women undergoing endometrial ablation should be informed that subsequent pregnancy may have serious complications and should be counselled to use reliable contraception after the procedure. TWEETABLE ABSTRACT: Systematic review - pregnancies reported after endometrial ablation have an increased risk of adverse outcomes.

Cumulative Effect of an Antimicrobial Stewardship and Rapid Diagnostic Testing Bundle on Early Streamlining of Antimicrobial Therapy in Gram-Negative Bloodstream Infections.

The use of rapid diagnostic tests (RDTs) enhances antimicrobial stewardship program (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluated the combined impact of an ASP/RDT bundle on the appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum antimicrobial agents (BSAA) in Gram-negative bloodstream infections (GNBSI). The ASP/RDT bundle consisted of system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and the FilmArray blood culture identification (BCID) panel. The preintervention period was January 2010 through December 2013, and the postintervention period followed from January 2014 through June 2015. The postintervention period was conducted in two phases; phase 1 followed the introduction of MALDI-TOF MS, and phase 2 followed the introduction of the FilmArray BCID panel. The interventions resulted in significantly improved appropriateness of EAT (95% versus 91%; P = 0.02). Significant reductions in median time to de-escalation from combination antimicrobial therapy (2.8 versus 1.5 days), antipseudomonal beta-lactams (4.0 versus 2.5 days), and carbapenems (4.0 versus 2.5 days) were observed in the postintervention compared to the preintervention period (P < 0.001 for all). The reduction in median time to de-escalation from combination therapy (1.0 versus 2.0 days; P = 0.03) and antipseudomonal beta-lactams (2.2 versus 2.7 days; P = 0.04) was further augmented during phase 2 compared to phase 1 of the postintervention period. Implementation of an antimicrobial stewardship program and RDT intervention bundle in a multihospital health care system is associated with improved appropriateness of EAT for GNBSI and decreased utilization of BSAA through early de-escalation.

Antibiotic loaded microspheres as antimicrobial delivery systems for medical applications.

In this paper, we present the preparation and antibiotic loading of polymeric microspheres, composed of copolymers derived from fatty acid/amino acid components, as new polymeric platforms for antibiotic delivery systems. New polymeric materials were used to prepare microspheres with and without immobilized model antibiotics (streptomycin, chloramphenicol and amphotericin B) by a W/O/W double-emulsion/solvent evaporation method, in which chloroform and poly(vinyl alcohol) are used as the solvent and emulsifier, respectively. The antimicrobial activity of the microspheres was tested against Gram-positive S. aureus, Gram-negative E. coli bacteria, and C. albicans, as a representative of a fungus. The new polymeric microspheres are particularly effective carriers for streptomycin, exhibiting antibacterial activity against all tested microorganisms.

Image movement of the Elekta EPID during gantry rotation: Effects on the verification of dose distributions.

PURPOSE: The use of Electronic Portal Imaging Devices (EPIDs) to acquire dosimetric information, especially for 3D-back-projection, has been increasingly extended. For a precise back-projection, the accurate knowledge of the movement characteristics of the EPID during gantry rotation is an essential requirement. METHODS AND MATERIAL: Measurements were conducted with different alignments of steel balls, which were mounted on the treatment table to avoid secondary effects such as the mechanical sag of gantry or jaws. The image movement of the EPID was determined by comparing the predicted projections of the phantoms with the EPID acquired image. Effects on dosimetric verifications were evaluated by γ-evaluation. RESULTS: The measurement results showed that the shift of the EPID image is larger in Y direction than in X direction. A maximum rotation of 0.3° and nodding of 2.4° of the detector was calculated. Changes in SDD were found up to 10mm. The angles of nodding are overall higher at discrete gantry angles in comparison to images detected for continuous rotation. Using these results we were able to correct the EPID images used for verification measurements. γ-evaluation revealed a significantly improved agreement between planned and measured EPID signal values. CONCLUSION: The measurement methods and algorithms introduced in this study are simple and comprehensive. Using these methods and algorithms we were able to quantify the major effects on geometrical and dosimetric characteristics. This allows the correction of EPID signal measurements for these effects related to the gantry angle, leading to an improved γ-evaluation for treatment plans.

Structure and thermal transitions in a biomedically relevant liquid crystalline poly(ester amide).

There is still a need to develop bioresorbable polymers with high strength and high modulus for load-bearing biomedical applications. Here we investigate the liquid crystalline structural features of poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate), poly(DTD DD), a new bioresorbable poly(ester amide) that is currently studied in vivo as a slow-degrading implantable biomaterial for load bearing applications. Thermally induced structural changes in poly(DTD DD) were studied using simultaneously differential scanning calorimetry (DSC) and X-ray scattering. The hexatic SmB organization of the polymer chains that exists at room temperature becomes progressively disordered upon heating, changing into a SmF phase and then into a smectic C phase at 60°C before turning into a free flowing melt at 130°C. X-ray scattering data and thermal analysis indicate the presence of a 2D ordered structure in the polymer melt. A structural model with an interesting 3-fold symmetry in the packing of the side chains around the rigid aromatic main chain, and the packing of these chains into fibrils is proposed. The liquid crystalline behavior of poly(DTD DD) makes it possible to melt process it at low temperatures without thermal degradation. This is a noteworthy advantage for the use of poly(DTD DD) as a high strength, readily processable, yet biodegradable polymer.

Immediate tangential excision accelerates wound closure but does not reduce scarring of mid-dermal porcine burns.

Current evidence supports the use of excision to remove eschar from deep dermal and full-thickness burns. However, the role of excision of mid-dermal burns remains unclear. This study aimed to develop a porcine model that could produce reproducible middermal thermal burns that undergo tangential excision; and investigate the effects of immediate tangential excision (30 minutes postburn) on healing and scarring. An aluminum bar preheated in hot water (70°C) was applied for 20 or 30 s to produce a total of sixteen mid-dermal burns per pig on each of six pigs. Thirty minutes after burn creation, half of the burns were tangentially excised. Four partial- thickness wounds per pig were created as controls. Depth of burn injury (1 and 24 h), reepithelialization (7 and 10 d) and scar depth (28 d) were assessed microscopically. Total scar surface area was grossly evaluated on day 28. Exposure of porcine skin to a preheated aluminum bar at 70 °C for 20 or 30 sec resulted in reproducible mid-dermal burns, where immediate excision enhanced complete wound closure as judged by complete re-epithelialization, but did not reduce initial depth of injury, scar contraction and scar depth. Immediate surgical intervention is sufficient to enhance wound closure, but not to mitigate mid-dermal burn scar formation. This work provides a suitable animal model to evaluate novel therapies that may be used to inhibit burn progression, accelerate wound closure and decrease scarring, especially those therapies unable to penetrate burn eschar.

Les données actuelles des connaissances sont en faveur de l'excision des brûlures des 2ème degré profond et 3ème degré. L'intérêt de l'excision des brûlures intermédiaires reste mal précisé. Cette étude se penche sur un modèle porcin destiné à la réalisation de brûlures intermédiaires reproductibles et à l'évaluation de l'effet l'excision ultra précoce (30 mn après la brûlure) sur l'épidermisation et la cicatrisation de ces brûlures. Six porcs ont subi chacun un total de 16 brûlures intermédiaires infligées au moyen d'une barre d'aluminium chauffée à 70°C et appliquée pendant 20 à 30 s. La moitié des zones brûlées étaient excisées à la trentième minute. Quatre brûlures superficielles servaient de contrôle. La profondeur de la brûlure (à h1 et h24), la réépithélialisation (à J7 et J10) et l'épaisseur de la cicatrice (à J28), étaient étudiées microscopiquement. La surface cicatricielle totale était évaluée à J28. L'exposition pendant 20 à 30s de la peau d'un porc à de l'aluminium préalablement chauffé à 70°C entraîne une brûlure intermédiaire reproductible. L'excision immédiate en favorise la guérison lorsqu'elle est jugée sur la réépithélialisation mais n'en réduit ni la profondeur, ni la rétraction cicatricielle, pas plus que l'épaisseur de la cicatrice. L'excision immédiate favorise la fermeture de la plaie mais pas son évolution vers des séquelles. Ce travail permet de décrire un modèle animal fiable dans le but d'évaluer de nouvelles thérapeutiques destinées à limiter le progression des lésions, accélérer la fermeture et diminuer la survenues de séquelles, en particulier celles incapables de pénétrer dans une lésion constituée.

Dual-component collagenous peptide/reactive oligomer hydrogels as potential nerve guidance materials - from characterization to functionalization.

Toward a new generation of improved nerve guidance conduits (NGCs), novel biomaterials are required to address pressing clinical shortcomings in peripheral nerve regeneration (PNR) and to promote biological performance. A dual-component hydrogel system formed by cross-linking reaction between maleic anhydride groups in an oligomeric building block for cross-linking of free amine functionalities in partially hydrolyzed collagen is formulated for continuous processing and NGC fabrication. The influence of the gelation base is optimized for processing from a double syringe delivery system with a static mixer. A hydrophilic low-concentrated base was introduced to control network formation and to utilize highly reactive macromers for gelation. Cross-linking extent and building block conversion were improved and homogenous monoliths were fabricated. Chemically derivatized hydrogels were obtained by conversion of a fraction of anhydride groups in the oligomeric precursor with monovalent primary amine-containing grafting molecules prior to gelation. Network stability in functionalized hydrogels was maintained and cationic moieties were implement to the gel that promoted in vitro cell attachment and spreading irrespective of mechanical stiffness. A molding strategy was introduced that allowed for fabrication of flexible tubular conduits in tunable dimensions and with chemically patterned structures. These hydrogel-based conduits hold promise for the next generation NGCs with integrated chemical cues for PNR.

Fungal Presence in Selected Tree Nuts and Dried Fruits.

Sixty-four tree nut samples (almonds, pecans, pine nuts, and walnuts) and 50 dried fruit samples (apricots, cranberries, papaya, pineapple, and raisins) were purchased from local supermarkets and analyzed for fungal contamination using conventional culture as well as molecular methods. The results of our study showed that the highest yeast and mold (YM) counts (5.34 log10 CFU g(-1)) were found in walnuts and the lowest in pecans. The most common mold in nuts was Aspergillus niger, relatively low numbers of A. flavus were found across the board, while Penicillium spp. were very common in pine nuts and walnuts. Low levels (2.00-2.84 log10 CFU g(-1)) of yeasts were recovered from only two pine nut samples. Fungal contamination in dried fruits was minimal (ranging from <2.00 to 3.86 log10 CFU g(-1)). The highest fungal levels were present in raisins. All papaya samples and the majority of cranberry, pineapple, and apricot samples were free of live fungi. The most common mold in dried fruits was A. niger followed by Penicillium spp. One apricot sample also contained low levels (2.00 log10 CFU g(-1)) of yeasts.

Impact of fluoroquinolone resistance in Gram-negative bloodstream infections on healthcare utilization.

There has been a concerning increase in fluoroquinolone resistance among Gram-negative bloodstream isolates. This retrospective cohort study examines the implications of fluoroquinolone resistance on use of healthcare resources in patients with Gram-negative bloodstream infections (BSI). Hospitalized adults with first episodes of community-onset Gram-negative BSI from 2010 to 2012 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate linear regression was used to examine risk factors for prolonged hospital length of stay (HLOS) in survivors of Gram-negative BSI. Among 474 unique patients, 384 (81%) and 90 (19%) had BSI due to fluoroquinolone-susceptible (FQ-S) and fluoroquinolone non-susceptible (FQ-NS) Gram-negative bacilli, respectively. The FQ-NS bloodstream isolates, particularly Escherichia coli, were more likely than FQ-S isolates to be multi-drug resistant (56% versus 6%, p < 0.001). Compared with patients with BSI due to FQ-S bloodstream isolates, those with FQ-NS isolates were more likely to receive inappropriate empirical antimicrobial therapy (26% versus 3%, p < 0.001), have longer mean HLOS (11.6 versus 9.3 days, p 0.03) and treatment duration with intravenous antibiotics during hospitalization (9.1 versus 7.1 days, p 0.001), and use outpatient intravenous antibiotics at hospital discharge (15% versus 8%, p 0.05). After adjustments in the multivariate model, inappropriate empirical antimicrobial therapy was an independent risk factor for prolonged HLOS in survivors of Gram-negative BSI (parameter estimate 3.65 days, 95% CI 0.43-6.86). Multi-drug resistance among FQ-NS bloodstream isolates limits both empirical and definitive antimicrobial treatment options and poses excessive burdens on the healthcare system.

Effect of dose reduction on image registration and image quality for cone-beam CT in radiotherapy.

INTRODUCTION: The additional radiation exposure applied to patients undergoing cone-beam computed tomography (CBCT) for image registration in radiation therapy is of great concern. Since a decrease in CBCT dose is linked to a degradation of image quality, the consequences of dose reduction on the registration process have to be investigated. MATERIAL AND METHODS: This paper examines image quality and registration of low-contrast structures on an Elekta XVI for the two treatment areas prostate and chest while gradually decreasing the mAs per frame and the number of projections per CBCT to achieve dose reduction. RESULTS: Ideal results for image quality were obtained for 1.6 mAs/frame and 377 projections in prostate scans and 0.63 mAs/frame and 440 projections in chest images. Lower as well as higher total mAs lead to a decrease in image quality. In spite of poor image quality, registration can be successfully performed even for lowest possible settings. CONCLUSION: The results for registration allow an extensive dose reduction in both treatment areas. Very low mAs, however, do not qualify for clinical use because subjective judgment of the registration process is impossible. Compared to default presets the use of settings for acceptable image quality already permit a decrease in exposure of about 40 % (29.0 to 16.7 mGy) in prostate scans and 60 % (18.3 to 7.7 mGy) in chest scans.

Tegaserod mimics the neurostimulatory glycan polysialic acid and promotes nervous system repair.

Glycans attached to the cell surface via proteins or lipids or exposed in the extracellular matrix affect many cellular processes, including neuritogenesis, cell survival and migration, as well as synaptic activity and plasticity. These functions make glycans attractive molecules for stimulating repair of the injured nervous system. Yet, glycans are often difficult to synthesize or isolate and have the disadvantage to be unstable in a complex tissue environment. To circumvent these issues, we have screened a library of small organic compounds to search for structural and functional mimetics of the neurostimulatory glycan polysialic acid (PSA) and identified the 5-HT4 receptor agonist tegaserod as a PSA mimetic. The PSA mimicking activity of tegaserod was shown in cultures of central and peripheral nervous system cells of the mouse and found to be independent of its described function as a serotonin (5-HT4) receptor agonist. In an in vivo model for peripheral nerve regeneration, mice receiving tegaserod at the site of injury showed enhanced recovery compared to control mice receiving vehicle control as evidenced by functional measurements and histology. These data indicate that tegaserod could be repurposed for treatment of nervous system injuries and underscores the potential of using small molecules as mimetics of neurostimulatory glycans.

Feasibility study of patient positioning verification in electron beam radiotherapy with an electronic portal imaging device (EPID).

The purpose of this study is to demonstrate the feasibility of verification and documentation in electron beam radiotherapy using the photon contamination detected with an electronic portal imaging device. For investigation of electron beam verification with an EPID, the portal images are acquired irradiating two different tissue equivalent phantoms at different electron energies. Measurements were performed on an Elekta SL 25 linear accelerator with an amorphous-Si electronic portal imaging device (EPID: iViewGT, Elekta Oncology Systems, Crawley, UK). As a measure of EPID image quality contrast (CR) and signal-to-noise ratio (SNR) are determined. For characterisation of the imaging of the EPID RW3 slabs and a Gammex 467 phantom with different material inserts are used. With increasing electron energy the intensity of photon contamination increases, yielding an increasing signal-to-noise ratio, but images are showing a decreasing contrast. As the signal-to-noise ratio saturates with increasing dose a minimum of 50 MUs is recommended. Even image quality depends on electron energy and diameter of the patient, the acquired results are mostly sufficient to assess the accuracy of beam positioning. In general, the online EPID acquisition has been demonstrated to be an effective electron beam verification and documentation method. The results are showing that this procedure can be recommended to be routinely and reliably done in patient treatment with electron beams.

Study of nanoscale structures in hydrated biomaterials using small-angle neutron scattering.

Distribution of water in three classes of biomedically relevant and degradable polymers was investigated using small-angle neutron scattering. In semicrystalline polymers, such as poly(lactic acid) and poly(glycolic acid), water was found to diffuse preferentially into the non-crystalline regions. In amorphous polymers, such as poly(d,l-lactic acid) and poly(lactic-co-glycolic acid), the scattering after 7 days of incubation was attributed to water in microvoids that form following the hydrolytic degradation of the polymer. In amorphous copolymers containing hydrophobic segments (desaminotyrosyl-tyrosine ethyl ester) and hydrophilic blocks (poly(ethylene glycol) (PEG)), a sequence of distinct regimes of hydration were observed: homogeneous distribution (∼10Å length scales) at <13 wt.% PEG (∼1 water per EG), clusters of hydrated domains (∼50Å radius) separated at 24 wt.% PEG (1-2 water per EG), uniformly distributed hydrated domains at 41 wt.% PEG (∼4 water per EG) and phase inversion at >50 wt.% PEG (>6 water per EG). Increasing the PEG content increased the number of these domains with only a small decrease in distance between the domains. These discrete domains appeared to coalesce to form submicron droplets at ∼60°C, above the melting temperature of crystalline PEG. The significance of such observations on the evolution of micrometer-size channels that form during hydrolytic erosion is discussed.