Tumour heterogeneity and immune-modulation.

Recent advances in sequencing technologies have revealed extensive intratumour heterogeneity (ITH) both within individual tumours and between primary and metastatic tumours for different cancer types. Such genetic diversity may have clinical implications for both cancer diagnosis and treatment with increasing evidence linking ITH and therapeutic resistance. Nonetheless, whilst limiting the activity of targeted agents, tumour genetic heterogeneity may provide a new therapeutic opportunity through generation of neo-antigens that could be recognised and targeted by the patient's own immune system in response to immune-modulatory therapies. Longitudinal genomic studies assessing tumour clonal architecture and its correlation with the underlying immune response to cancer in each particular patient are needed to follow tumour evolutionary dynamics over time and through therapy, in order to further understand the mechanisms behind drug resistance and to inform the development of new combinatorial therapeutic strategies

Statistical optimization of process parameters for the production of citric acid from oil palm empty fruit bunches

In this study, optimization of process parameters such as moisture content, incubation temperature and initial pH (fixed) for the improvement of citric acid production from oil palm empty fruit bunches through solid state bioconversion was carried out using traditional one-factor-at-a-time (OFAT) method and response surface methodology (RSM). The possible optimum level of moisture content, incubation temperature, and initial pH were found from the OFAT study to be 70%, 30 - 32oC and 5.5 - 8, respectively. The optimum moisture content of 70.3% (v/w) and incubation temperature of 33.1°C with initial pH of 6.5 gave the maximum production of citric acid (369.16 g/kg of dry EFB). The analysis of variance (ANOVA) of the statistical optimization using central composite design showed that moisturecontent (p<0.001) and incubation temperature (p<0.0001) as well as the interaction of these two parameters were highly significant for the citric acid production

Fracture Risk Assessment in Chronic Kidney Disease, Prospective Testing Under Real World Environments (FRACTURE): a prospective study

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is associated with an increased risk of fracture. Decreased bone mass and disruption of microarchitecture occur early in the course of CKD and worsens with the progressive decline in renal function so that at the time of initiation of dialysis at least 50% of patients have had a fracture. Despite the excess fracture risk, and the associated increases in morbidity and mortality, little is known about the factors that are associated with an increase in fracture risk. Our study aims to identify prognostic factors for bone loss and fractures in patients with stages 3 to 5 CKD.</p> <p>Methods</p> <p>This prospective study aims to enroll two hundred and sixty men and women with stages 3 to 5 CKD. Subjects will be followed for 24 months and we will examine the ability of: 1) bone mineral density by dual x-ray absorptiometry at the spine, hip, and radius; 2) volumetric bone density by high resolution peripheral quantitated computed tomography at the radius and tibia; 3) serum markers of bone turnover; 4) bone formation rate by bone biopsy; and 5) muscle strength and balance to predict spine and non-spine fractures, identified by self-report and/or vertebral morphometry. All measurements will be obtained at baseline, at 12 and at 24 months with the exception of bone biopsy, which will be measured once at 12 months. Subjects will be contacted every 4 months to determine if there have been incident fractures or falls.</p> <p>Discussion</p> <p>This study is one of the first that aims to identify risk factors for fracture in early stage CKD patients. Ultimately, by identifying risk factors for fracture and targeting treatments in this group-before the initiation of renal replacement therapy - we will reduce the burden of disease due to fractures among patients with CKD.</p

Tongue carcinoma in an adult Down's syndrome patient: a case report

<p>Abstract</p> <p>Background</p> <p>Cancer of the oral cavity is rare and unusual in Down's syndrome patient. The over all risk is similar to that in adult population.</p> <p>Case presentation</p> <p>This case report describes a 27 years old male with Down's syndrome, non-smoker, who developed a poorly differentiated squamous cell carcinoma of the tongue. The patient underwent a hemiglossectomy without neck dissection followed by a postoperative locoregional radiation therapy to a total tumor-bed dose of 56 Gy and 45 Gy to the neck. Three months later, the patient presented with local tongue recurrence and was treated by Docetaxel and Carboplatin chemotherapy with no significant response. The patient died one month later, 9 months after his initial diagnosis.</p> <p>Conclusion</p> <p>To our knowledge, this is the first case of tongue carcinoma arising in a patient with Down's syndrome. This unique case might not be sufficient to make a significant conclusion on the prognosis and survival of these patients but will increase the awareness about this possibility and will help in the appropriate management of Down's syndrome patients.</p

Dosimetric effect of intra-fractional and inter-fractional target motion in lung cancer radiotherapy techniques

Purpose: The purpose of present study was to experimentally evaluate the dosimetric uncertainties in 3-dimensional conformal radiotherapy (3DCRT), dynamic intensity modulated radiotherapy (D-IMRT), step-shoot (SS-IMRT), and volumetric modulated arc therapy (VMAT) treatment delivery techniques due to intra- and inter-fractional target motion. Methods: A previously treated lung patient was selected for this study and was replanned for 60 Gy in 30 fractions using four techniques (3DCRT, D-IMRT, SS-IMRT, and VMAT). These plans were delivered in a clinical linear accelerator equipped with HexaPOD™ evo RT System. The target dose of static QUASAR phantom was calculated that served as reference dose to the target. The QUASAR respiratory body phantom along with patients breathing wave form and HexaPOD™ evo RT System was used to simulate the intra-fraction and inter-fraction motions. Dose measurements were done by applying the intra-fractional and inter-fractional motions in all the four treatment delivery techniques.Results: The maximum percentage deviation in a single field was -4.3%, 10.4%, and -12.2% for 3DCRT, D-IMRT and SS-IMRT deliveries, respectively. Similarly, the deviation for a single fraction was -1.51%, -1.88%, -2.22%, and -3.03% for 3DCRT, D-IMRT, SS-IMRT and VMAT deliveries, respectively. Conclusion: The impact of inter-fractional and intra-fractional uncertainties calculated as deviation between dynamic and static condition dose was large in some fractions, however average deviation calculated for thirty fractions was well within 0.5% in all the four techniques. Therefore, inter- and intra-fractional uncertainties could be concern in fewer fraction treatments such as stereotactic body radiation therapy, and should be used in conjunction with intra- and inter-fractional motion management techniques

Custom-designed orthopedic implants evaluated using finite element analysis of patient-specific computed tomography data: femoral-component case study

<p>Abstract</p> <p>Background</p> <p>Conventional knee and hip implant systems have been in use for many years with good success. However, the custom design of implant components based on patient-specific anatomy has been attempted to overcome existing shortcomings of current designs. The longevity of cementless implant components is highly dependent on the initial fit between the bone surface and the implant. The bone-implant interface design has historically been limited by the surgical tools and cutting guides available; and the cost of fabricating custom-designed implant components has been prohibitive.</p> <p>Methods</p> <p>This paper describes an approach where the custom design is based on a Computed Tomography scan of the patient's joint. The proposed design will customize both the articulating surface and the bone-implant interface to address the most common problems found with conventional knee-implant components. Finite Element Analysis is used to evaluate and compare the proposed design of a custom femoral component with a conventional design.</p> <p>Results</p> <p>The proposed design shows a more even stress distribution on the bone-implant interface surface, which will reduce the uneven bone remodeling that can lead to premature loosening.</p> <p>Conclusion</p> <p>The proposed custom femoral component design has the following advantages compared with a conventional femoral component. (i) Since the articulating surface closely mimics the shape of the distal femur, there is no need for resurfacing of the patella or gait change. (ii) Owing to the resulting stress distribution, bone remodeling is even and the risk of premature loosening might be reduced. (iii) Because the bone-implant interface can accommodate anatomical abnormalities at the distal femur, the need for surgical interventions and fitting of filler components is reduced. (iv) Given that the bone-implant interface is customized, about 40% less bone must be removed. The primary disadvantages are the time and cost required for the design and the possible need for a surgical robot to perform the bone resection. Some of these disadvantages may be eliminated by the use of rapid prototyping technologies, especially the use of Electron Beam Melting technology for quick and economical fabrication of custom implant components.</p

A relative value method for measuring and evaluating cardiac reserve

BACKGROUND: Although a very close relationship between the amplitude of the first heart sound (S1) and the cardiac contractility have been proven by previous studies, the absolute value of S1 can not be applied for evaluating cardiac contractility. However, we were able to devise some indicators with relative values for evaluating cardiac function. METHODS: Tests were carried out on a varied group of volunteers. Four indicators were devised: (1) the increase of the amplitude of the first heart sound after accomplishing different exercise workloads, with respect to the amplitude of the first heart sound (S1)recorded at rest was defined as cardiac contractility change trend (CCCT). When the subjects completed the entire designed exercise workload (7000 J), the resulting CCCT was defined as CCCT(1); when only 1/4 of the designed exercise workload was completed, the result was defined as CCCT(1/4). (2) The ratio of S1 amplitude to S2 amplitude (S1/S2). (3) The ratio of S1 amplitude at tricuspid valve auscultation area to that at mitral auscultation area T1/M1 (4) the ratio of diastolic to systolic duration (D/S). Data were expressed as mean ± SD. RESULTS: CCCT(1/4) was 6.36 ± 3.01 (n = 67), CCCT(1) was 10.36 ± 4.2 (n = 33), S1/S2 was1.89 ± 0.94 (n = 140), T1/M1 was 1.44 ± 0.99 (n = 144), and D/S was 1.68 ± 0.27 (n = 172). CONCLUSIONS: Using indicators CCCT(1/4) and CCCT(1) may be beneficial for evaluating cardiac contractility and cardiac reserve mobilization level, S1/S2 for considering the factor for hypotension, T1/M1 for evaluating the right heart load, and D/S for evaluating diastolic cardiac blood perfusion time

Lithiated porous silicon nanowires stimulate periodontal regeneration

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline