Using deep learning for pruning region detection and plant organ segmentation in dormant spur-pruned grapevines.

Even though mechanization has dramatically decreased labor requirements, vineyard management costs are still affected by selective operations such as winter pruning. Robotic solutions are becoming more common in agriculture, however, few studies have focused on grapevines. This work aims at fine-tuning and testing two different deep neural networks for: (i) detecting pruning regions (PRs), and (ii) performing organ segmentation of spur-pruned dormant grapevines. The Faster R-CNN network was fine-tuned using 1215 RGB images collected in different vineyards and annotated through bounding boxes. The network was tested on 232 RGB images, PRs were categorized by wood type (W), orientation (Or) and visibility (V), and performance metrics were calculated. PR detection was dramatically affected by visibility. Highest detection was associated with visible intermediate complex spurs in Merlot (0.97), while most represented coplanar simple spurs allowed a 74% detection rate. The Mask R-CNN network was trained for grapevine organs (GOs) segmentation by using 119 RGB images annotated by distinguishing 5 classes (cordon, arm, spur, cane and node). The network was tested on 60 RGB images of light pruned (LP), shoot-thinned (ST) and unthinned control (C) grapevines. Nodes were the best segmented GOs (0.88) and general recall was higher for ST (0.85) compared to C (0.80) confirming the role of canopy management in improving performances of hi-tech solutions based on artificial intelligence. The two fine-tuned and tested networks are part of a larger control framework that is under development for autonomous winter pruning of grapevines. Supplementary Information: The online version contains supplementary material available at 10.1007/s11119-023-10006-y.

The Impact of COVID-19 on Radiotherapy Services in Scotland, UK: A Population-based Study.

AIMS: The effect of the COVID-19 pandemic on cancer radiotherapy services is largely unknown. The aim of the present study was to investigate the impact of the resultant contingency plans on radiotherapy cancer services in Scotland. MATERIALS AND METHODS: Detailed data of radiotherapy activity at our centre were collected from 1 April 2019 to 31 March 2021. Differences in mean weekly radiotherapy courses, dose and fractionation patterns and treatment intent were compared with corresponding pre-pandemic months for all treatment sites. Qualitative data were collected for a subgroup of radical radiotherapy patients. RESULTS: Total radiotherapy courses decreased from 6968 to 6240 (-10%) compared with the previous year, prior to the pandemic. Average weekly radiotherapy courses delivered were 134 (standard deviation ±13), decreasing by 10% to 120 (standard deviation 15) (Welch's t-test, P < 0.001). The greatest decrease in new start treatment courses was observed from May to August 2020 (-7.7%, -24.0%, -16.7% and -18.7%) compared with the corresponding months in 2019. A significant reduction was seen for female patients <70 years (-16%) compared with females >70 years (-8%) or their male counterparts (-7% and -6%, respectively). By diagnosis, the largest reductions between pre- and post-pandemic levels were for anal (-26%), breast (-18%) and prostate (-14%) cancer. Contrarily, a significant increase was found for bladder (28%) and oesophageal (11%) cancers. CONCLUSIONS: Over the first 12 months of the COVID-19 pandemic, radiotherapy activity significantly decreased compared with the 12 months prior. Due to issued guidance, the use of hypofractionated regimens increased, contributing to the reduction in treatments for some tumour sites. An increase in other tumour sites can probably be attributed to the reduction or cancellation of surgical interventions. These results will inform our understanding of the indirect consequences of the pandemic on radiotherapy services.

A statistical alternative to current measures of image quality in digital mammography.

Objective. Mammogram image quality in European breast screening systems is defined by threshold gold thickness (T) assessment of the CDMAM contrast-detail phantom. Previous studies have outlined several limitations of the phantom including expense, number of images required and inter-phantom manufacturing variability. Two alternative approaches to image quality assessment for routine quality control are examined and compared to the CDMAM technique: (i) A detectability index (d') based on a non-prewhitened model observer with an eye filter (NPWE) and(ii) A statistical estimate of contrast based on image noise levels (CSTAT).Approach. Thed' calculation follows a previously published methodology based on the NNPS and contrast, both measured from an image of 5 cm of PMMA containing a 0.2 mm Al target, as well as the MTF measured under standard conditions. For the proposed statistical method, pixels in the centre of the same NNPS image were re-binned into a range of equivalent CDMAM target areas. For any area, the minimum contrast necessary to distinguish a signal from the background,CSTAT, is 3.29σat a 95% level of confidence, whereσis the standard deviation of the background pixels. Theoretical analysis predicts a simple relationships betweenCSTAT,Tandd'. Measured values ofCSTATwere compared toTandd' as a function of air kerma at the detector for ten digital mammography systems from three different manufacturers.Main Results. Theoretical relationships betweenCSTAT,d' andTwere demonstrated. Minimum acceptable image quality performance for 0.10 and 0.25 mm diameter discs, defined by the European Guidelines in terms ofT, are equivalent tod' values of 0.85 and 5.36 and thresholdCSTATvalues of 0.055 and 0.022.Significance. Strong correlations between log(T), log(d') and log(CSTAT) suggest that either alternative approach produces information corresponding to that obtained using the CDMAM.CSTATshould be considered as a simple, objective and cost-effective alternative to routine image quality assessment in mammography.

A one-generation reproductive toxicity study of the mycotoxin ochratoxin A in Fischer rats.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium molds. Grain-based foods account for most human dietary exposures to OTA. OTA is a teratogen, but its reproductive and developmental effects are poorly understood. A one-generation reproductive toxicity study was conducted with groups of 16 male and 16 female Fischer rats exposed to 0, 0.026, 0.064, 0.16, 0.4 or 1.0 mg OTA/kg in diet. Dams exposed to 1.0 mg OTA/kg diet had statistically significant F1 pup losses between implantation and postnatal day (PND 4). Delays in preputial separation (PPS) and vaginal opening (VO) were indicative of delayed puberty in F1 rats. Mild renal lesions in nursing pups indicated that exposure prior to weaning impacted the kidneys. The developing kidney was more susceptible to OTA than the adult kidney. Significant increases in multi-oocyte follicles (MOFs) and proportional changes in resting and growing follicles were observed in F1 female ovaries. Plasma testosterone was reduced in F0 males, and there were negative effects on sperm quality in F0 and F1 male rats. The results confirm that continuous dietary exposure to OTA causes post-implantation fetotoxicity in dams, and renal and reproductive toxicity in their male and female offspring.

Signal recovery from stimulation artifacts in intracranial recordings with dictionary learning.

OBJECTIVE: Electrical stimulation of the human brain is commonly used for eliciting and inhibiting neural activity for clinical diagnostics, modifying abnormal neural circuit function for therapeutics, and interrogating cortical connectivity. However, recording electrical signals with concurrent stimulation results in dominant electrical artifacts that mask the neural signals of interest. Here we develop a method to reproducibly and robustly recover neural activity during concurrent stimulation. We concentrate on signal recovery across an array of electrodes without channel-wise fine-tuning of the algorithm. Our goal includes signal recovery with trains of stimulation pulses, since repeated, high-frequency pulses are often required to induce desired effects in both therapeutic and research domains. We have made all of our code and data publicly available. APPROACH: We developed an algorithm that automatically detects templates of artifacts across many channels of recording, creating a dictionary of learned templates using unsupervised clustering. The artifact template that best matches each individual artifact pulse is subtracted to recover the underlying activity. To assess the success of our method, we focus on whether it extracts physiologically interpretable signals from real recordings. MAIN RESULTS: We demonstrate our signal recovery approach on invasive electrophysiologic recordings from human subjects during stimulation. We show the recovery of meaningful neural signatures in both electrocorticographic (ECoG) arrays and deep brain stimulation (DBS) recordings. In addition, we compared cortical responses induced by the stimulation of primary somatosensory (S1) by natural peripheral touch, as well as motor cortex activity with and without concurrent S1 stimulation. SIGNIFICANCE: Our work will enable future advances in neural engineering with simultaneous stimulation and recording.

Rat strain response differences upon exposure to technical or alpha hexabromocyclododecane.

Hexabromocyclododecane (HBCD) is a brominated flame retardant which was recommended by a UN expert body under the Stockholm Convention to be eliminated from the global marketplace in 2011; however, due to its ability to persist in the environment, undergo long-range transport and bioaccumulate, it remains a concern for human health. The commercial mix of HBCD (T-HBCD) consists of α-HBCD, ß-HBCD and γ-HBCD. Although the γ-HBCD (79%) isomer is the predominant isomer of T-HBCD, the most bioaccumulative isomer detected in mammals is the α-HBCD isomer. This study was undertaken to investigate three rat strains treated with commercial grade (technical) HBCD or HBCD enriched with the α isomer (A-HBCD) and to examine strain- and sex-related differences in response to exposure. Female Sprague Dawley (SD), Wistar (WI) and Fischer F344 (FI) rats were exposed for 28 days to either T-HBCD or A-HBCD in feed, at doses of 0, 250, 1250 and 5000 mg/kg diet. The FI rodent strain was found to be the most sensitive to effects of HBCD based on the greatest number of significantly affected endpoints which indicated that T-HBCD primarily affected liver and thyroid, resulting in multiple health effects. Consequently, male FI were included in the study and exposed to T- and A-HBCD. Histopathological data supports previously reported effects of HBCD on the thyroid and endocrine system although the effects in FI rats are significantly elevated compared to other strains. As with T-HBCD, liver and thyroid were found to be target organs of A-HBCD. Sex differences, specifically in tissue concentration levels, immune response parameters and in number and severity of thyroid and liver lesions, following exposure to either T- or A-HBCD were apparent, with treatment eliciting a greater response in males. Residue analysis revealed that α-HBCD is more bioaccumulative than γ-HBCD in all rodent strains, with levels of HBCD in animals treated with A-HBCD several fold higher for all tissues tested (7-11 fold at the highest dose). Thus, residue data supports the selective uptake (implies there are differences in bioavailability and/or bioaccumulation; is this the case or do certain isomers simply have a longer half-life) of specific isomers, with α-HBCD > γ-HBCD. Taken together, our study highlights the importance of selecting the most appropriate strain and of including both sexes in studies to ensure that sex-related differences in response to test chemical is taken into consideration. Moreover, ours is the first study to show the effects of a sub-acute exposure to a diet containing only HBCD enriched for the α isomer, which better represents the isomer ratios present in the biota due to bioaccumulation.

Study of Patients Self-Training Influence on Peripheral Neuropathies Diseases Diagnosis through D.I.T.A Device.

In our daily life, the sight and the sense of touch play a fundamental role in objects recognitions. This process is helped by the experience: if a subject has already seen or already touched an object in the past, he will recognize it more easily in the future. Following this assumption, the authors of this paper wanted to investigate if the experience can influence the results of a clinical examination where the subject has an active role. The attention was focused on the peripheral neuropathies diagnosis since they require an accurate assessment of several parameters including the tactile sensitivity trend. In other words, if the tests encompass an active role of the subjects, one of the main uncertainties is the self-training that influences the subject responses. This work focuses on the study of this self-training using the D.I.T.A device (Dynamic Investigation Test-rig on hAptics). Results clearly show a fundamental role of priming during "haptic modality": expert subjects, previously experienced with the tests, demonstrated better recognition of the encountered stimuli, compared to novices. Moreover, the results show that the maximum difference between the two groups of subjects is in the first part of the test. An ANOVA analysis was carried out to demonstrate that also the errors between the pins-arrays are affected by the priming.

Network meta-analysis in health psychology and behavioural medicine: a primer.

Progress in the science and practice of health psychology depends on the systematic synthesis of quantitative psychological evidence. Meta-analyses of experimental studies have led to important advances in understanding health-related behaviour change interventions. Fundamental questions regarding such interventions have been systematically investigated through synthesising relevant experimental evidence using standard pairwise meta-analytic procedures that provide reliable estimates of the magnitude, homogeneity and potential biases in effects observed. However, these syntheses only provide information about whether particular types of interventions work better than a control condition or specific alternative approaches. To increase the impact of health psychology on health-related policy-making, evidence regarding the comparative efficacy of all relevant intervention approaches - which may include biomedical approaches - is necessary. With the development of network meta-analysis (NMA), such evidence can be synthesised, even when direct head-to-head trials do not exist. However, care must be taken in its application to ensure reliable estimates of the effect sizes between interventions are revealed. This review paper describes the potential importance of NMA to health psychology, how the technique works and important considerations for its appropriate application within health psychology.

Results from the Super Cryogenic Dark Matter Search Experiment at Soudan.

We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.

A 90-day subchronic gavage toxicity study in Fischer 344 rats with 3-methylfuran.

A 90-day gavage study was conducted with 0.0, 0.02, 0.075, 0.25, 1.0 and 4.0 mg/kg bw/day dose groups of 3-methylfuran to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including changes in gross anatomy, histopathology, clinical biochemistry and hematology. There were significant changes in the serum clinical biochemistry markers related to liver injury where males were more affected than the females for most parameters analysed. The serum liver injury marker γ-glutamyltransferase, alanine and aspartate aminotransferases were significantly increased in males in the 4.0 mg/kg dose group. Alkaline phosphatase was increased in females and males. There were increases in both gross and histological lesions in the liver of both sexes in addition to statistical differences in female liver weights at the 4.0 mg/kg bw/day dose. Significant increases in spleen weights were found in both genders. This was accompanied by a dose-dependent atrophy of both B- and T-cell regions in which the males were more affected. There were no significant changes in male kidney weights but there was microscopically decreased protein in the proximal tubules and crowding of their nuclei in the 4.0 mg/kg bw/day dose group. There were also significant changes in the kidney serum biomarkers including various electrolytes, blood urea nitrogen, creatinine and uric acid. A small, but significant increase in female kidney weights was observed and which increase was accompanied by changes in electrolytes, kidney specific markers and a dose-dependent increase in mineralization. In both genders, amylase decreased whereas lipase increased but these were not accompanied by any histological changes in the pancreas. Histopathological changes in the liver were observed consistently in male and female rats in the 0.25 mg/kg dose group and higher. Hence, a lowest observed adverse effect level (LOAEL) of 0.25 mg/kg bw/d and a no observed adverse effect level (NOAEL) of 0.075 mg/kg bw/day are proposed for 3-methylfuran-induced hepatic lesions in this study. Benchmark dose modelling based on a BMR of 10% change in lesion incidence, generated BMDLs10 of 0.08 mg/kg bw/day in male rats and 0.05-0.17 mg/kg bw/day in female rats for increased incidence of liver lesions.

The identification of fungi collected from the ceca of commercial poultry.

Under normal conditions, fungi are ignored unless a disease/syndrome clinical signs are reported. The scientific communities are largely unaware of the roles fungi play in normal production parameters. Numerous preharvest interventions have demonstrated that beneficial bacteria can play a role in improving productions parameters; however, most researchers have ignored the impact that fungi may have on production. The goal of the present study was to record fungi recovered from commercial broiler and layer houses during production. Over 3,000 cecal samples were isolated using conventional culture methodology and over 890 samples were further characterized using an automated repetitive sequence-based PCR (rep-PCR) methodology. Eighty-eight different fungal and yeast species were identified, including Aspergillus spp., Penicillium spp., and Sporidiobolus spp, and 18 unknown genera were separated using rep-PCR. The results from the present study will provide a normal fungi background genera under commercial conditions and will be a stepping stone for investigating the impact of fungi on the gastrointestinal tract and on the health of poultry.

The development and assessment of the Worry About Pain Questionnaire.

BACKGROUND: Worry can be conceptualized as a cognitive-affective automatic process initiated in order to address uncertainty and potential personal inadequacies that could result in negative outcomes. The purpose of the current study was to develop a measure of pain-specific worry - the Worry About Pain Questionnaire (WAPQ). METHOD: In study 1, responses of 335 pain-free participants were used to complete an item analysis and exploratory factors analysis to develop and assess the internal structure of the WAPQ. Study 2 included 224 pain-free participants who completed the WAPQ in order to confirm its factor structure, and to examine its relation to the experience of acute experimental pain. In study 3, 137 individuals with persistent pain were asked to complete the WAPQ as well as measures of pain and depressive symptoms. RESULTS: The resulting 15-item measure assesses uncertainties and potential negative outcomes related to the experience of pain. The results of the exploratory and confirmatory factor analyses showed a two-factor structure. Across all studies, the WAPQ was found to be related to measures of pain in clinical and non-clinical samples, acute experimental pain stimuli, as well as pain anxiety, pain catastrophizing, fear of pain, rumination and depressive symptomatology. CONCLUSIONS: The results suggest that the WAPQ is a reliable and valid measure for the assessment of worry about pain that can be used to understand how pain-specific worries are related to the experience and impact of pain across different populations. SIGNIFICANCE: Worry has been assessed in pain populations using measures that assess worry in general. The current study shows a relationship between pain-specific worry and the experience of pain. Further, worry about pain is related to but not synonymous with pain catastrophizing.

Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice.

Deoxynivalenol (DON) is a secondary metabolite associated with Fusarium species pathogenic to important food crops. A two-year feeding study reported that DON was non-carcinogenic in B6C3F1 mice. The present study was conducted to further characterize the chronic effects of DON by exposing cancer-prone transgenic p53 heterozygous (p53+/-) male mice and p53 homozygous (p53+/+) male mice to 0, 1, 5, or 10 mg DON/kg in diet for 26 weeks. Gross and microscopic organ-specific neoplastic and non-neoplastic changes and expression profiles of key hepatic and renal genes were assessed. Few toxicologic differences between p53+/+ and p53+/- mice were observed, and no tumours were observed due to DON. The results indicated that DON was non-carcinogenic and that reduced expression of the p53 gene did not play a key role in responses to DON toxicity. The lack of inflammatory and proliferative lesions in mice may be attributed to the anorectic effects of DON, which resulted in dose-dependent reductions in body weight in p53+/+ and p53+/- mice. Hepatic and renal gene expression analyses confirmed that chronic exposure to DON was noninflammatory. The effects of 26-week DON exposure on p53+/+ and p53+/-mice were consistent with those previously seen in B6C3F1 mice exposed to DON for two years.

Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation.

OBJECTIVE: To investigate the effects of pain coping skills training (PCST) and a lifestyle behavioral weight management (BWM) program on inflammatory markers and biomarker associations with pain and function in the OA LIFE study. METHOD: Serum samples were available from a subset (N = 169) of the overweight or obese knee OA participants in the OA LIFE study that evaluated: PCST, BWM, combined PCST + BWM, or standard care (SC). Inflammatory markers (hsCRP, IL-1ra, IL-1ß, IL-6, IL-8, TNF-α, TNFRI, TNFRII, and hyaluronic acid (HA)), and adipokines (leptin and adiponectin) were measured before and after the 24-week treatment period. Biomarkers were assessed for effects of treatment and for associations with change in weight, pain and disability (unadjusted and adjusted for age, race, sex, baseline body mass index (BMI), and baseline biomarker concentration). RESULTS: PCST + BWM was associated with significant reductions in hsCRP (P = 0.0014), IL-6 (P = 0.0075), and leptin (P = 0.0001). After adjustment, there was a significant effect of PCST + BWM on changes in leptin (b = -0.19, P = 0.01) and IL-6 (b = -0.25, P = 0.02) relative to SC. Reductions in leptin and IL-6 were significantly correlated with reductions in weight, BMI and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain; reductions in IL-6 were correlated with improvements in WOMAC and Arthritis Impact Measurement Scales (AIMS) physical function. By mediation analyses, weight loss was responsible for 54% of the change in IL-6 and all of the change in leptin. CONCLUSIONS: OA-related inflammatory markers were reduced by a 24-week combined PCST + BWM intervention. This suggests that the inflammatory state can be successfully modified in the context of a readily instituted clinical intervention with a positive clinical outcome.

Methods to induce labour: a systematic review, network meta-analysis and cost-effectiveness analysis.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 µg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 µg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost.

New Results from the Search for Low-Mass Weakly Interacting Massive Particles with the CDMS Low Ionization Threshold Experiment.

The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c^{2}.

First direct limits on lightly ionizing particles with electric charge less than e/6.

While the standard model of particle physics does not include free particles with fractional charge, experimental searches have not ruled out their existence. We report results from the Cryogenic Dark Matter Search (CDMS II) experiment that give the first direct-detection limits for cosmogenically produced relativistic particles with electric charge lower than e/6. A search for tracks in the six stacked detectors of each of two of the CDMS II towers finds no candidates, thereby excluding new parameter space for particles with electric charges between e/6 and e/200.

A checklist for critical appraisal of indirect comparisons.

The aim of this study was to develop a user-friendly checklist for critical appraisal of indirect comparisons of drugs, considering clinical, methodological/statistical and quality aspects, mainly to be applied in drug evaluation in the decision-making context. After conducting a review of the literature, we used group consensus to establish the key points of the checklist, focusing mainly on indirect comparisons, but including topics related to network meta-analysis or multiple treatment comparisons. The coordinating group elaborated the first draft, which was reviewed by external experts, re-evaluated by the coordinating group and finally assessed by 23 drug evaluation experts trained in indirect comparisons, who applied the checklist to one study. The Kappa index of agreement was calculated and the final checklist was developed by group consensus including the external experts. The checklist has two parts. The first consists of three eliminatory key questions while the second includes 17 items: 5 regarding quality, 5 regarding clinical issues and 7 dealing with methodology/statistics. The median kappa values of the 23 evaluations were 0.83 (range 0.67-0.93), 0.61 (0.54-0.91) and 0.36 (0.22-1) with regard to quality, clinical aspects and methodology/statistics, respectively. A structured checklist was developed to facilitate critical appraisal of key issues in indirect comparisons, including comments for assessing the consequences of its application to drug evaluation in the decision-making context. Agreement between reviewers in clinical and quality items was good, but weaker in methodology/statistics ones.

Vasculogenesis and Angiogenesis in Modular Collagen-Fibrin Microtissues.

The process of new blood vessel formation is critical in tissue development, remodeling and regeneration. Modular tissue engineering approaches have been developed to enable the bottom-up assembly of more complex tissues, including vascular networks. In this study, collagen-fibrin composite microbeads (100-300 µm in diameter) were fabricated using a water-in-oil emulsion technique. Human endothelial cells and human fibroblasts were embedded directly in the microbead matrix at the time of fabrication. Microbead populations were characterized and cultured for 14 days either as free-floating populations or embedded in a surrounding fibrin gel. The collagen-fibrin matrix efficiently entrapped cells and supported their viability and spreading. By 7 days in culture, endothelial cell networks were evident within microbeads, and these structures became more prominent by day 14. Fibroblasts co-localized with endothelial cells, suggesting a pericyte-like function, and laminin deposition indicated maturation of the vessel networks over time. Microbeads embedded in a fibrin gel immediately after fabrication showed the emergence of cells and the coalescence of vessel structures in the surrounding matrix by day 7. By day 14, inosculation of neighboring cords and prominent vessel structures were observed. Microbeads pre-cultured for 7 days prior to embedding in fibrin gave rise to vessel networks that emanated radially from the microbead by day 7, and developed into connected networks by day 14. Lumen formation in endothelial cell networks was confirmed using confocal sectioning. These data show that collagen-fibrin composite microbeads support vascular network formation. Microbeads embedded directly after fabrication emulated the process of vasculogenesis, while the branching and joining of vessels from pre-cultured microbeads resembled angiogenesis. This modular microtissue system has utility in studying the processes involved in new vessel formation, and may be developed into a therapy for the treatment of ischemic conditions.

Search for low-mass weakly interacting massive particles with SuperCDMS.

We report a first search for weakly interacting massive particles (WIMPs) using the background rejection capabilities of SuperCDMS. An exposure of 577 kg days was analyzed for WIMPs with mass <30 GeV/c(2), with the signal region blinded. Eleven events were observed after unblinding. We set an upper limit on the spin-independent WIMP-nucleon cross section of 1.2×10(-42) cm(2) at 8 GeV/c(2). This result is in tension with WIMP interpretations of recent experiments and probes new parameter space for WIMP-nucleon scattering for WIMP masses <6 GeV/c(2).