In Vitro Mechanical Studies of Implantable Truss Technology for Total Knee Arthroplasty Designs

Total Knee Arthroplasty (TKA) is a common treatment for patients with severe knee pain due to osteoarthritis, a condition characterized by the loss of articular cartilage or injury. Most patients that opt to proceed with a TKA procedure report effective pain mitigation; however, approximately 30% do not realize sufficient pain relief following the procedure. This post-operative pain is typically associated with fixation, integration, and mechanical complications that can lead to a loss of bone mass. In cases where the procedure is successful, a revision procedure may still be required as the lifespan of the device is limited to 10-20 years when problems with fixation culminate in total failure of the device. The proposed research will evaluate a TKA device that incorporates unique geometrical and mechanical properties that address the problems associated with initial and long-term fixation, as well as component wear. Consequently, this technology is expected to enhance the quality of life of the patient, as well as potentially eliminate the need for revision procedures

Intelligent techniques using molecular data analysis in leukaemia: an opportunity for personalized medicine support system

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient’s genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.Haneen Banjar, David Adelson, Fred Brown, and Naeem Chaudhr

A study of cervical Papanicolaou smears examination in patients with abnormal vaginal discharge

Background: Reproductive tract infection represents major public health problem in developing countries. Cervical infections are common problems among women of reproductive age and associated with clinical complaints of vaginal discharge. Pap smear is a screening test to diagnose various abnormal pathology of cervix. Aims and objectives of this study was to identify various causes of vaginal discharge and frequency of various pathogenic microorganisms in cervical smear.Methods: This was hospital based descriptive study carried out on 300 female patients who attended obstetrics and gynecology clinic at tertiary care hospital with compliant of vaginal discharge. Cervical smear samples were collected, conventional smears were prepared by trained technical staff and stained using Papanicolaou (Pap) technique.Results: The most common age group affected with vaginal discharge was 26 to 35 years with 115 cases. The most common associated symptom was lower abdominal pain seen in 75 cases. Most frequent findings on per speculum examination was thick whitish discharge in 186 cases and the most common pathogenic organism found was Bacterial Vaginosis (BV) in 177 cases.Conclusions: The study emphasizes the need for educating women of rural community to raise the awareness for cervical Pap screening

Modelling predictors of molecular response to frontline imatinib for patients with chronic myeloid leukaemia

BACKGROUND: Treatment of patients with chronic myeloid leukaemia (CML) has become increasingly difficult in recent years due to the variety of treatment options available and challenge deciding on the most appropriate treatment strategy for an individual patient. To facilitate the treatment strategy decision, disease assessment should involve molecular response to initial treatment for an individual patient. Patients predicted not to achieve major molecular response (MMR) at 24 months to frontline imatinib may be better treated with alternative frontline therapies, such as nilotinib or dasatinib. The aims of this study were to i) understand the clinical prediction 'rules' for predicting MMR at 24 months for CML patients treated with imatinib using clinical, molecular, and cell count observations (predictive factors collected at diagnosis and categorised based on available knowledge) and ii) develop a predictive model for CML treatment management. This predictive model was developed, based on CML patients undergoing imatinib therapy enrolled in the TIDEL II clinical trial with an experimentally identified achieving MMR group and non-achieving MMR group, by addressing the challenge as a machine learning problem. The recommended model was validated externally using an independent data set from King Faisal Specialist Hospital and Research Centre, Saudi Arabia. PRINCIPLE FINDINGS: The common prognostic scores yielded similar sensitivity performance in testing and validation datasets and are therefore good predictors of the positive group. The G-mean and F-score values in our models outperformed the common prognostic scores in testing and validation datasets and are therefore good predictors for both the positive and negative groups. Furthermore, a high PPV above 65% indicated that our models are appropriate for making decisions at diagnosis and pre-therapy. Study limitations include that prior knowledge may change based on varying expert opinions; hence, representing the category boundaries of each predictive factor could dramatically change performance of the models.Haneen Banjar, Damith Ranasinghe, Fred Brown, David Adelson, Trent Kroger, Tamara Leclercq, Deborah White, Timothy Hughes, Naeem Chaudhr

Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit

Aim The anastomosis technique used following right-sided colonic resection is widely variable and may affect patient outcome. This study aimed to assess the association between leak and anastomosis technique (stapled vs handsewn). Method This was a prospective, multicentre, international audit including patients undergoing elective or emergency right hemicolectomy or ileo-caecal resection operations over a 2-month period in early 2015. The primary outcome measure was the presence of anastomotic leak within 30 days of surgery, determined using a prespecified definition. Mixed effects logistic regression models were used to assess the association between leak and anastomosis method, adjusting for patient, disease and operative cofactors, with centre included as a random-effect variable. Results This study included 3208 patients, of whom 78.4% (n = 2515) underwent surgery for malignancy and 11.7% (n = 375) underwent surgery for Crohn's disease. An anastomosis was performed in 94.8% (n = 3041) of patients, which was handsewn in 38.9% (n = 1183) and stapled in 61.1% (n = 1858). Patients undergoing hand-sewn anastomosis were more likely to be emergency admissions (20.5% handsewn vs 12.9% stapled) and to undergo open surgery (54.7% handsewn vs 36.6% stapled). The overall anastomotic leak rate was 8.1% (245/3041), which was similar following handsewn (7.4%) and stapled (8.5%) techniques (P = 0.3). After adjustment for cofactors, the odds of a leak were higher for stapled anastomosis (adjusted OR = 1.43; 95% CI: 1.04-1.95; P = 0.03). Conclusion Despite being used in lower-risk patients, stapled anastomosis was associated with an increased anastomotic leak rate in this observational study. Further research is needed to define patient groups in whom a stapled anastomosis is safe.This is the peer-reviewed version of the article: Pinkney, T.; Battersby, N.; Bhangu, A.; Chaudhri, S.; El-Hussuna, A.; Frasson, M.; Nepogodiev, D.; Singh, B.; Kovačević, B.; Autora), (i Jos Puno. Relationship between Method of Anastomosis and Anastomotic Failure after Right Hemicolectomy and Ileo-Caecal Resection: An International Snapshot Audit. Colorectal Disease 2017, 19 (8), O296–O311. [https://doi.org/10.1111/codi.13646

Dosimetric precision of an ion beam tracking system

<p>Abstract</p> <p>Background</p> <p>Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams.</p> <p>Methods</p> <p>A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion.</p> <p>Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system.</p> <p>Results</p> <p>All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements.</p> <p>Conclusions</p> <p>The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems.</p

Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats

Conditioned behavioral responses to discrete drug-associated cues can be modulated by the environmental context in which those cues are experienced, a process that may facilitate relapse in humans. Rodent models of drug self-administration have been adapted to reveal the capacity of contexts to trigger drug seeking, thereby enabling neurobiological investigations of this effect. We tested the hypothesis that dopamine transmission in the nucleus accumbens, a neural structure that mediates reinforcement, is necessary for context-induced reinstatement of responding for ethanol-associated cues. Rats pressed one lever (active) for oral ethanol (0.1 ml; 10% v/v) in operant conditioning chambers distinguished by specific visual, olfactory, and tactile contextual stimuli. Ethanol delivery was paired with a discrete (4 s) light-noise stimulus. Responses on a second lever (inactive) were not reinforced. Behavior was then extinguished by withholding ethanol but not the discrete stimulus in a different context. Reinstatement, expressed as elevated responding for the discrete stimulus without ethanol delivery, was tested by placing rats into the prior self-administration context after administration of saline or the dopamine D1 receptor antagonist, SCH 23390 (0.006, 0.06, and 0.6 μg/side), into the nucleus accumbens core or shell. Compared with extinction responding, active lever pressing in saline-pretreated rats was enhanced by placement into the prior ethanol self-administration context. SCH 23390 dose-dependently reduced reinstatement after infusion into the core or shell. These findings suggest a critical role for dopamine acting via D1 receptors in the nucleus accumbens in the reinstatement of responding for ethanol cues triggered by placement into an ethanol-associated context

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial

Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800–1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400–1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44–64], p=0·013 for PRB28; 58/103 [56%, 44–66], p=0·005 for PR4/PRB24; 69/103 [67%, 57–76], p<0·0001 for PRB48; and 77/103 [75%, 65–83], p<0·0001 for PR4/PRB44; vs 39/104 [38%, 28–48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine of 104 [9%]) than did the control group. In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Merck