Computer-assisted pathological immunohistochemistry scoring is more time-effective than conventional scoring, but provides no analytical advantage

Computer-assisted pathological immunohistochemistry scoring is more time-effective than conventional scoring, but provides no analytical advantage

Accelerated partial breast irradiation (APBI): Are breath-hold and volumetric radiation therapy techniques useful?

Background: In a selective group of patients accelerated partial breast irradiation (APBI) might be applied after conservative breast surgery to reduce the amount of irradiated healthy tissue. The role of volumetric modulated arc therapy (VMAT) and voluntary moderately deep inspiration breath-hold (vmDIBH) techniques in further reducing irradiated healthy – especially heart – tissue is investigated.

Material and methods: For 37 partial breast planning target volumes (PTVs), three-dimensional conformal radiotherapy (3D-CRT) (3 – 5 coplanar or non-coplanar 6 and/or 10 MV beams) and VMAT (two partial 6 MV arcs) plans were made on CTs acquired in free-breathing (FB) and/or in vmDIBH. Dose-volume parameters for the PTV, heart, lungs, and breasts were compared. 

Results: Better dose conformity was achieved with VMAT compared to 3D-CRT (conformity index 1.24 0.09 vs. 1.49 0.20). Non-PTV ipsilateral breast receiving 50% of the prescribed dose was on average reduced by 28% in VMAT plans compared to 3D-CRT plans. Mean heart dose (MHD) reduced from 2.0 (0.1 – 5.1) Gy in 3D-CRT(FB) to 0.6 (0.1 – 1.6) Gy in VMAT(vmDIBH). VMAT is benefi cial for MHD reduction if MHD with 3D-CRT exceeds 0.5Gy. Cardiac dose reduction as a result of VMAT increases with increasing initial MHD, and adding vmDIBH reduces the cardiac dose further. Mean dose to the ipsilateral lung decreased from 3.7 (0.7 – 8.7) to 1.8 (0.5 – 4.0) Gy with VMAT(vmDIBH) compared to 3D-CRT(FB). VMAT resulted in a slight increase in the contralateral breast dose (DMean ) always remaining 1.9 Gy). 

Conclusions: For APBI patients, VMAT improves PTV dose conformity and delivers lower doses to the ipsilateral breast and lung compared to 3D-CRT. This goes at the cost of a slight but acceptable increase of the contralateral breast dose. VMAT reduces cardiac dose if MHD exceeds 0.5 Gy for 3D-CRT. Adding vmDIBH results in a further reduction of heart and ipsilateral lung dose. 

Assisted Diagnosis of Cervical Intraepithelial Neoplasia (CIN)

This paper introduces an automated computer- assisted system for the diagnosis of cervical intraepithelial neoplasia (CIN) using ultra-large cervical histological digital slides. The system contains two parts: the segmentation of squamous epithelium and the diagnosis of CIN. For the segmentation, to reduce processing time, a multiresolution method is developed. The squamous epithelium layer is first segmented at a low (2X) resolution. The boundaries are further fine tuned at a higher (20X) resolution. The block-based segmentation method uses robust texture feature vectors in combination with support vector machines (SVMs) to perform classification. Medical rules are finally applied. In testing, segmentation using 31 digital slides achieves 94.25% accuracy. For the diagnosis of CIN, changes in nuclei structure and morphology along lines perpendicular to the main axis of the squamous epithelium are quantified and classified. Using multi-category SVM, perpendicular lines are classified into Normal, CIN I, CIN II, and CIN III. The robustness of the system in term of regional diagnosis is measured against pathologists' diagnoses and inter-observer variability between two pathologists is considered. Initial results suggest that the system has potential as a tool both to assist in pathologists' diagnoses, and in training.

Barriers to student computer usage: staff and student perceptions

Ensuring that all graduates are able to exploit new technologies is a primary goal of all UK universities and a variety of assumptions have underpinned policies designed to promote this goal, This paper explores some of these assumptions through the findings of a. longitudinal study involving a cohort of over 800 university students. The study adopted a student perspective to examine the factors affecting their use of computers over a three year period. Unsurprisingly, the results indicated that situational factors (e.g. access, training and time) influence the extent to which students use computers, but a disparity was found in the importance attributed to these factors by the academic staff, who focused on the needs of their department, and by the students, who focused on their individual needs. Results suggest that increased attention to a student perspective may lead to improved strategic planning in students' use of computers.

Implementation of phantom-less IMRT delivery verification using Varian DynaLog files and R/V output

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at -0.03-0.12 mm for prostate and -0.02-0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Single vocal cord irradiation:a competitive treatment strategy in early glottic cancer

INTRODUCTION: The treatment of choice for early glottic cancer is still being debated; ultimately it relies on the functional outcome. This paper reports on a novel sparing 4D conformal technique for single vocal cord irradiation (SVCI).

MATERIAL AND METHODS: The records of 164 T1a patients with SCC of the vocal cord, irradiated in the Erasmus MC between 2000 and 2008, were analyzed for local control and overall survival. The quality of life was determined by EORTC H&N35 questionnaires. Also the VHI (voice handicap index), and the TSH (thyroid stimulating hormone) blood levels, were established. On-line image guided SVCI, using cone beam CT or stereotactic radiation therapy (SRT) techniques, were developed.

RESULTS: A LC rate at five-years of 93% and a VHI of 12.7 (0-63) was determined. It appeared feasible to irradiate one vocal cord within 1-2mm accuracy. This way sparing of the contralateral (CL) vocal cord and CL normal tissues, could be achieved.

CONCLUSIONS: Given the accuracy (1-2mm) and small volume disease (CTV limited to one vocal cord), for the use of stereotactic RT techniques SVCI with large fraction sizes is currently being investigated in clinic. It is argued that hypofractionated SVCI can be a competitive alternative to laser surgery.

Time Efficient Assessment and Feedback Methods for Large Computer-Aided-Design Cohorts

Timely and individualized feedback on coursework is desirable from a student perspective as it facilitates formative development and encourages reflective learning practice. Faculty however are faced with a significant and potentially time consuming challenge when teaching larger cohorts if they are to provide feedback which is timely, individualized and detailed. Additionally, for subjects which assess non-traditional submissions, such as Computer-Aided-Design (CAD), the methods for assessment and feedback tend not to be so well developed or optimized. Issues can also arise over the consistency of the feedback provided. Evaluations of Computer-Assisted feedback in other disciplines (Denton et al, 2008), (Croft et al, 2001) have shown students prefer this method of feedback to traditional “red pen” marking and also that such methods can be more time efficient for faculty.
Herein, approaches are described which make use of technology and additional software tools to speed up, simplify and automate assessment and the provision of feedback for large cohorts of first and second year engineering students studying modules where CAD files are submitted electronically. A range of automated methods are described and compared with more “manual” approaches. Specifically one method uses an application programming interface (API) to interrogate SolidWorks models and extract information into an Excel spreadsheet, which is then used to automatically send feedback emails. Another method describes the use of audio recordings made during model interrogation which reduces the amount of time while increasing the level of detail provided as feedback.
Limitations found with these methods and problems encountered are discussed along with a quantified assessment of time saving efficiencies made.

Non-pharmacological interventions for cognitive impairment due to systemic cancer treatment (Review)

Background

It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
Objectives

To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
Search methods

We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
Selection criteria

Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
Data collection and analysis

Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
Main results

Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I2= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I2 = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I2 = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I2 = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
Authors' conclusions

Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Cryopreservation of human semen and prepared sperm: effects on motility parameters and DNA integrity

Objective: To investigate effects of cryopreservation on sperm motility and DNA integrity. Design: Pre-cryopreservation and post-cryopreservation analysis of motility and DNA integrity of semen and prepared sperm samples. Setting: A hospital andrology laboratory. Patient(s): Forty men attending the Regional Fertility Centre, Belfast, Northern Ireland. Intervention(s): Each sample was divided, and an aliquot was frozen unprepared. Remaining aliquots were prepared by Percoll density centrifugation (95.0:47.5) or direct swim-up procedure and divided into aliquots to allow direct comparison of fresh and frozen semen and prepared sperm (frozen with or without the addition of seminal plasma) from the same ejaculate. Samples were frozen by static-phase vapor cooling and being plunged into liquid nitrogen. Thawing was carried out at room temperature. Main Outcome Measure(s): Sperm DNA integrity was determined using a modified alkaline single cell gel electrophoresis (comet) assay, and motility was determined using computer-assisted semen analysis. Result(s): Sperm frozen unprepared in seminal fluid appeared more resistant to freezing damage than frozen prepared sperm. Further improvements can be achieved by selecting out the subpopulation of sperm with best motility and DNA integrity and freezing these sperm in seminal plasma, making this the optimal procedure. Conclusion(s): Freezing sperm in seminal plasma improves postthaw motility and DNA integrity.

The Effects of Delta–9–Tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro.

Objective: to investigate the effects of tetrahydrocannabinol; THC on human sperm function in vitro. Design: laboratory analysis of sperm motility with and without exposure to THC using computer assisted semen analysis (CASA) and acrosome reaction by fluoroscein isothiocyanate labelled peanut agglutinin (FITC-PNA) staining. Setting: An ART unit in a tertiary medical centre. Patients: semen was obtained from 78 men attending the Regional Fertility Centre, Belfast. Interventions: Sperm were divided into 90% (the best fertilizing potential used in assisted conception) and 45% (the poorer subpopulation) fractions by density centrifugation and incubated with, or without (controls), tetrahydrocannabinol (THC) at concentrations equivalent to therapeutic (0.032�?�¯?�?�­M) and recreational (4.8 and 0.32�?�¯?�?�­M) plasma levels, at 37�?�¯?�?�°C for 3 hours. Main outcome measures: Sperm motility, spontaneous and induced acrosome reactions Results: There was a dose-dependent decrease in percentage progressive motility (-21% at 4.8�??�?�µM, p0.05) in the 90% fraction. The 45% fraction showed a greater decrease in percentage progressive motility (-56% at 4.8�??�?�µM, p=0.011; -23% at 0.32�??�?�µM, p= 0.039; and -28% at 0.032�??�?�µM, p=0.004). A decrease in the straight line velocity; VSL (-10%) and the average path velocity; VAP (-10%) were also observed in the 90% fraction. A significant inhibition (-15% at 4.8�??�?�µM, p=0.04) in spontaneous acrosome reaction was observed in the 90% fraction. The 45% fraction showed a more marked inhibition [-35% (p

Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro

Objective: to determine if sildenafil citrate; a cyclic monophosphate specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. Design: laboratory analysis of sperm motility after exposure to sildenafil citrate using computer assisted semen analysis (CASA) and acrosome reaction by fluoroscein isothiocyanate labelled peanut agglutinin (FITC-PNA) staining. Setting: An ART unit Patients: 57 male patients Interventions: Sperm were divided into 90% (the best fertilizing potential used in assisted conception) and 45% (the poorer subpopulation) fractions by density centrifugation and incubated with sildenafil citrate ( 0.67uM) at 37ï?°C for up to 180 minutes. Main outcome measures: both the numbers and velocity of progressively motile sperm were significantly increased by sildenafil citrate between 15 and 135 minutes. Further, samples revealed that these effects were consistent in the 90% and 45% subpopulations of sperm. In both subpopulations, sildenafil also caused a significant increase in the proportion of acrosome reacted sperm - 22.1% compared with 11.8% in the control group of the good quality fraction (p

Validation of membrane protein topology models by oxidative labeling and mass spectrometry

Computer-assisted topology predictions are widely used to build low-resolution structural models of integral membrane proteins (IMPs). Experimental validation of these models by traditional methods is labor intensive and requires modifications that might alter the IMP native conformation. This work employs oxidative labeling coupled with mass spectrometry (MS) as a validation tool for computer-generated topology models. ·OH exposure introduces oxidative modifications in solvent-accessible regions, whereas buried segments (e.g., transmembrane helices) are non-oxidizable. The Escherichia coli protein WaaL (O-antigen ligase) is predicted to have 12 transmembrane helices and a large extramembrane domain (Pérez et al., Mol. Microbiol. 2008, 70, 1424). Tryptic digestion and LC-MS/MS were used to map the oxidative labeling behavior of WaaL. Met and Cys exhibit high intrinsic reactivities with ·OH, making them sensitive probes for solvent accessibility assays. Overall, the oxidation pattern of these residues is consistent with the originally proposed WaaL topology. One residue (M151), however, undergoes partial oxidation despite being predicted to reside within a transmembrane helix. Using an improved computer algorithm, a slightly modified topology model was generated that places M151 closer to the membrane interface. On the basis of the labeling data, it is concluded that the refined model more accurately reflects the actual topology of WaaL. We propose that the combination of oxidative labeling and MS represents a useful strategy for assessing the accuracy of IMP topology predictions, supplementing data obtained in traditional biochemical assays. In the future, it might be possible to incorporate oxidative labeling data directly as constraints in topology prediction algorithms.