Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units : cost effectiveness evaluation

Objective: To assess the cost-effectiveness of screening, isolation and decolonisation strategies in the control of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs). Design: Economic evaluation. Setting: England and Wales. Population: ICU patients. Main outcome measures: Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost-effectiveness ratios for alternative strategies, net monetary benefits (NMBs). Results: All strategies using isolation but not decolonisation improved health outcomes but increased costs. When MRSA prevalence on admission to the ICU was 5% and the willingness to pay per QALY gained was between £20,000 and £30,000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or following identification by admission and weekly MRSA screening using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction (PCR)-based MRSA detection coupled with isolation was unlikely to be cost-effective unless prevalence was high (10% colonised with MRSA on admission to the ICU). All decolonisation strategies improved health outcomes and reduced costs. While universal decolonisation (regardless of MRSA status) was the most cost-effective in the short-term, strategies using screening to target MRSA carriers may be preferred due to reduced risk of selecting for resistance. Amongst such targeted strategies, universal admission and weekly PCR screening coupled with decolonisation with nasal mupirocin was the most cost-effective. This finding was robust to ICU size, MRSA admission prevalence, the proportion of patients classified as high-risk, and the precise value of willingness to pay for health benefits. Conclusions: MRSA control strategies that use decolonisation are likely to be cost-saving in an ICU setting provided resistance is lacking, and combining universal PCR-based screening with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In ICUs where decolonisation is not implemented there is insufficient evidence to support universal MRSA screening outside high prevalence settings.

Cerclage, evolution and potential of a Cinderella Technology : an overview with reference to periprosthetic fractures

Periprosthetic fractures are increasingly frequent. The fracture may be located over the shaft of the prosthesis, at its tip or below (21). The treatment of explosion fractures is difficult because the shaft blocks the application of implants, like screws, which need to penetrate the medullary cavity. The cerclage, as a simple periosteal loop, made of wire or more recently cable, does not only avoid the medullary cavity. Its centripetal mode of action is well suited for reducing and maintaining radially displaced fractures. Furthermore, the cerclage lends itself well for minimally invasive internal fixation. New insight challenges the disrepute of which the cerclage technology suffered for decades. The outcome of cerclage fixation benefits from an improved understanding of its technology, mechano-biology and periosteal blood supply. Preconceived and generally accepted opinions like "strangulation of blood supply" need to be re-examined. Recent mechanical evaluations (22) demonstrate that the wire application may be improved but cable is superior in hand- ling, maintenance of tension and strength. Beside the classical concepts of absolute and relative stability a defined stability condition needs consideration. It is typical for cerclage. Called "loose-lock stability" it specifies the situation where a loosened implant allows first unimpeded displacement changing abruptly into a locked fixation preventing further dislocation.

Hyaluronic acid : evaluation as a potential delivery vehicle for vitronectin:growth factor complexes in wound healing applications

We have previously reported that novel vitronectin:growth factor (VN:GF) complexes significantly increase re-epithelialization in a porcine deep dermal partial-thickness burn model. However, the potential exists to further enhance the healing response through combination with an appropriate delivery vehicle which facilitates sustained local release and reduced doses of VN:GF complexes. Hyaluronic acid (HA), an abundant constituent of the interstitium, is known to function as a reservoir for growth factors and other bioactive species. The physicochemical properties of HA confer it with an ability to sustain elevated pericellular concentrations of these species. This has been proposed to arise via HA prolonging interactions of the bioactive species with cell surface receptors and/or protecting them from degradation. In view of this, the potential of HA to facilitate the topical delivery of VN:GF complexes was evaluated. Two-dimensional (2D) monolayer cell cultures and 3D de-epidermised dermis (DED) human skin equivalent (HSE) models were used to test skin cell responses to HA and VN:GF complexes. Our 2D studies revealed that VN:GF complexes and HA stimulate the proliferation of human fibroblasts but not keratinocytes. Experiments in our 3D DED-HSE models showed that VN:GF complexes, both alone and in conjunction with HA, led to enhanced development of both the proliferative and differentiating layers in the DED-HSE models. However, there was no significant difference between the thicknesses of the epidermis treated with VN:GF complexes alone and VN:GF complexes together with HA. While the addition of HA did not enhance all the cellular responses to VN:GF complexes examined, it was not inhibitory, and may confer other advantages related to enhanced absorption and transport that could be beneficial in delivery of the VN:GF complexes to wounds.

Development of an autonomous unmanned aerial system to collect time-stamped samples from the atmosphere and localize potential pathogen sources

This paper presents the hardware development and testing of a new concept for air sampling via the integration of a prototype spore trap onboard an unmanned aerial system (UAS).We propose the integration of a prototype spore trap onboard a UAS to allow multiple capture of spores of pathogens in single remote locations at high or low altitude, otherwise not possible with stationary sampling devices.We also demonstrate the capability of this system for the capture of multiple time-stamped samples during a single mission.Wind tunnel testing was followed by simulation, and flight testing was conducted to measure and quantify the spread during simulated airborne air sampling operations. During autonomous operations, the onboard autopilot commands the servo to rotate the sampling device to a new indexed location once the UAS vehicle reaches the predefined waypoint or set of waypoints (which represents the region of interest). Time-stamped UAS data are continuously logged during the flight to assist with analysis of the particles collected. Testing and validation of the autopilot and spore trap integration, functionality, and performance is described. These tools may enhance the ability to detect new incursions of spores

Comparing the cost-effectiveness of MRSA control strategies between ICU and non-ICU settings

Introduction / objectives Many strategies are used to control MRSA in hospitals. Only a few have been assessed in clinical trials and it is not obvious how findings should be generalised between settings. Uncertainty remains about which strategies represent the most appropriate use of scarce resources. We assess the cost-effectiveness of alternative MRSA screening and infection control strategies in England and Wales and discuss international relevance. Methods Models of MRSA transmission in ICUs and general medical (GM) wards were developed and used to evaluate different screening methods combined with decolonisation or isolation. Strategies were compared in terms of costs and health benefits (quality adjusted life years, QALYs). Different prevalences, proportions of high risk patients and ward sizes were investigated, and probabilistic sensitivity analyses (PSA) conducted. Results Decolonisation strategies were cost-saving in ICUs at a 5% admission prevalence, with admission and weekly PCR screening the most cost-effective (£3,929/QALY). In ICUs, screening and isolation reduced infection rates by ~10%. With admission prevalence ≤5%, targeting screening and isolation to high risk patients was optimal. In GM wards decolonisation and isolation strategies, though able to reduce MRSA infection rates up to ~50%, were not cost-effective. Conclusion The largest reductions in MRSA infection were achieved by screening and decolonisation strategies, and were cost-effective in ICU settings. In comparison, there is limited potential for screening and control strategies to be cost-effective in GM wards due to lower infection and mortality rates.

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be inappropriate for transplantation strategies.

A conceptual model for manufacturing performance improvement

Purpose: Important performance objectives manufacturers sought can be achieved through adopting the appropriate manufacturing practices. This paper presents a conceptual model proposing relationship between advanced quality practices, perceived manufacturing difficulties and manufacturing performances. Design/methodology/approach: A survey-based approach was adopted to test the hypotheses proposed in this study. The selection of research instruments for inclusion in this survey was based on literature review, the pilot case studies and relevant industrial experience of the author. A sample of 1000 manufacturers across Australia was randomly selected. Quality managers were requested to complete the questionnaire, as the task of dealing with the quality and reliability issues is a quality manager’s major responsibility. Findings: Evidence indicates that product quality and reliability is the main competitive factor for manufacturers. Design and manufacturing capability and on time delivery came second. Price is considered as the least important factor for the Australian manufacturers. Results show that collectively the advanced quality practices proposed in this study neutralize the difficulties manufacturers face and contribute to the most performance objectives of the manufacturers. The companies who have put more emphasize on the advanced quality practices have less problem in manufacturing and better performance in most manufacturing performance indices. The results validate the proposed conceptual model and lend credence to hypothesis that proposed relationship between quality practices, manufacturing difficulties and manufacturing performances. Practical implications: The model shown in this paper provides a simple yet highly effective approach to achieving significant improvements in product quality and manufacturing performance. This study introduces a relationship based ‘proactive’ quality management approach and provides great potential for managers and engineers to adopt the model in a wide range of manufacturing organisations. Originality/value: Traditional ways of checking product quality are different types of testing, inspection and screening out bad products after manufacturing them. In today’s manufacturing where product life cycle is very short, it is necessary to focus on not to manufacturing them first rather than screening out the bad ones. This study introduces, for the first time, the idea of relationship based advanced quality practices (AQP) and suggests AQPs will enable manufacturers to develop reliable products and minimize the manufacturing anomalies. This paper explores some of the attributes of AQP capable of reducing manufacturing difficulties and improving manufacturing performances. The proposed conceptual model contributes to the existing knowledge base of quality practices and subsequently provides impetus and guidance towards increasing manufacturing performance.

Raising awareness of traffic pollution: the potential benefits and problems of using a warning smell

Exposure to traffic pollution is increasing worldwide as people move to cities, and as more vehicles join the roads, creating longer journeys and more traffic jams. Most traffic pollutants are odourless and invisible, which hides exposure from the public. If traffic pollution had a distinctive smell it would enable people to avoid exposure, and increase the political will for difficult policy changes. A smell may also instigate longer-term changes, such as switching to active transport for school pick-ups. A smell could be added using a fuel additive or a temporary device attached to vehicle exhausts.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

The development of a conceptual framework for a district 4-Year Pavement Management Plan, implementation of network-level project screening process

The Texas Department of Transportation (TxDOT) is concerned about the widening gap between preservation needs and available funding. Funding levels are not adequate to meet the preservation needs of the roadway network; therefore projects listed in the 4-Year Pavement Management Plan must be ranked to determine which projects should be funded now and which can be postponed until a later year. Currently, each district uses locally developed methods to prioritize projects. These ranking methods have relied on less formal qualitative assessments based on engineers’ subjective judgment. It is important for TxDOT to have a 4-Year Pavement Management Plan that uses a transparent, rational project ranking process. The objective of this study is to develop a conceptual framework that describes the development of the 4-Year Pavement Management Plan. It can be largely divided into three Steps; 1) Network-Level project screening process, 2) Project-Level project ranking process, and 3) Economic Analysis. A rational pavement management procedure and a project ranking method accepted by districts and the TxDOT administration will maximize efficiency in budget allocations and will potentially help improve pavement condition. As a part of the implementation of the 4-Year Pavement Management Plan, the Network-Level Project Screening (NLPS) tool including the candidate project identification algorithm and the preliminary project ranking matrix was developed. The NLPS has been used by the Austin District Pavement Engineer (DPE) to evaluate PMIS (Pavement Management Information System) data and to prepare a preliminary list of candidate projects for further evaluation.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers : a potential marker of physical activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic / anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3 / endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk / survival.

The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

Validity of the malnutrition screening tool for older adults at high risk of hospital readmission

Malnutrition is a serious problem in older adults, particularly for those at risk of hospital readmission. The essential step in managing malnutrition is early identification using a valid nutrition screening tool. The purpose of this study was to validate the Malnutrition Screening Tool (MST) in older adults at high risk of hospital readmission. Two registered nurses administered the MST to identify malnutrition risk, and compared it to the comprehensive Subjective Global Assessment (SGA) to assess nutritional status for patients aged 65 years who had at least one risk factor for hospital readmission. The MST demonstrates substantial sensitivity, specificity and agreement with the SGA. These findings indicate that nursing staff can use the MST as a valid tool for routine screening and rescreening to identify patients at risk of malnutrition. Use of the MST may prevent hospital-acquired malnutrition for acute hospitalized older adults at high risk of readmission.