987 resultados para Sections 10


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Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: ⢠Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. ⢠The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. ⢠The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

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Internationally, collection of reliable data on new and evolving health-care roles is crucial. We describe a protocol for design and administration of a national census of an emergent health-care role, namely nurse practitioners in Australia using databases held by regulatory authorities. A questionnaire was developed to obtain data on the role and scope of practice of Australian nurse practitioners. Our tool comprised five sections and included a total of 56 questions, using 28 existing items from the National Nursing and Midwifery Labour Force Census and nine items recommended in the Nurse Practitioner Workforce Planning Minimum Data Set. Australian Nurse Registering Authorities (n = 6) distributed the survey on our behalf. This paper outlines our instrument and methods. The survey was administered to 238 authorized Australian nurse practitioners (85% response rate). Rigorous collection of standardized items will ensure health policy is informed by reliable and valid data. We will re-administer the survey 2 years following the first survey to measure change over time.

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Background: Early pregnancy loss has been linked to enduring psychological morbidity. Aims: This study aimed to investigate the utility of the Kessler 10 (K10) questionnaire as a brief screening instrument to identify women at risk for the development of psychiatric diagnoses three months post-miscarriage. Method: Participants were 117 consecutive women presenting at a public hospital emergency department and receiving a diagnosis of miscarriage. Main outcome measures: K10 screen for psychological distress and the Structured Clinical Interview for DSM Disorders to determine psychiatric diagnoses. Results: A majority of women (81.2%) experienced elevated levels of distress initially, 24.8% in the very high range. They were not at increased risk of psychiatric diagnoses at three months compared with the general population; however, they were significantly more likely to report subsyndromal symptoms at this time compared with the general population. The baseline K10 score was the only significant predictor of distress at follow-up (r = 0.45, P < 0.001). The receiver operating characteristic curve shows that a cut-off of 14 on the K10 has suitable sensitivity (97%) and specificity (82%) for predicting ongoing psychological distress in women who miscarry. Conclusions: The K10 is effective in identifying women at risk for ensuring psychological symptoms following miscarriage.

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Considerable past research has explored relationships between vehicle accidents and geometric design and operation of road sections, but relatively little research has examined factors that contribute to accidents at railway-highway crossings. Between 1998 and 2002 in Korea, about 95% of railway accidents occurred at highway-rail grade crossings, resulting in 402 accidents, of which about 20% resulted in fatalities. These statistics suggest that efforts to reduce crashes at these locations may significantly reduce crash costs. The objective of this paper is to examine factors associated with railroad crossing crashes. Various statistical models are used to examine the relationships between crossing accidents and features of crossings. The paper also compares accident models developed in the United States and the safety effects of crossing elements obtained using Korea data. Crashes were observed to increase with total traffic volume and average daily train volumes. The proximity of crossings to commercial areas and the distance of the train detector from crossings are associated with larger numbers of accidents, as is the time duration between the activation of warning signals and gates. The unique contributions of the paper are the application of the gamma probability model to deal with underdispersion and the insights obtained regarding railroad crossing related vehicle crashes. Considerable past research has explored relationships between vehicle accidents and geometric design and operation of road sections, but relatively little research has examined factors that contribute to accidents at railway-highway crossings. Between 1998 and 2002 in Korea, about 95% of railway accidents occurred at highway-rail grade crossings, resulting in 402 accidents, of which about 20% resulted in fatalities. These statistics suggest that efforts to reduce crashes at these locations may significantly reduce crash costs. The objective of this paper is to examine factors associated with railroad crossing crashes. Various statistical models are used to examine the relationships between crossing accidents and features of crossings. The paper also compares accident models developed in the United States and the safety effects of crossing elements obtained using Korea data. Crashes were observed to increase with total traffic volume and average daily train volumes. The proximity of crossings to commercial areas and the distance of the train detector from crossings are associated with larger numbers of accidents, as is the time duration between the activation of warning signals and gates. The unique contributions of the paper are the application of the gamma probability model to deal with underdispersion and the insights obtained regarding railroad crossing related vehicle crashes.

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A composite line source emission (CLSE) model was developed to specifically quantify exposure levels and describe the spatial variability of vehicle emissions in traffic interrupted microenvironments. This model took into account the complexity of vehicle movements in the queue, as well as different emission rates relevant to various driving conditions (cruise, decelerate, idle and accelerate), and it utilised multi-representative segments to capture the accurate emission distribution for real vehicle flow. Hence, this model was able to quickly quantify the time spent in each segment within the considered zone, as well as the composition and position of the requisite segments based on the vehicle fleet information, which not only helped to quantify the enhanced emissions at critical locations, but it also helped to define the emission source distribution of the disrupted steady flow for further dispersion modelling. The model then was applied to estimate particle number emissions at a bi-directional bus station used by diesel and compressed natural gas fuelled buses. It was found that the acceleration distance was of critical importance when estimating particle number emission, since the highest emissions occurred in sections where most of the buses were accelerating and no significant increases were observed at locations where they idled. It was also shown that emissions at the front end of the platform were 43 times greater than at the rear of the platform. Although the CLSE model is intended to be applied in traffic management and transport analysis systems for the evaluation of exposure, as well as the simulation of vehicle emissions in traffic interrupted microenvironments, the bus station model can also be used for the input of initial source definitions in future dispersion models.

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While externally moderated standards-based assessment has been practised in Queensland senior schooling for more than three decades, there has been no such practice in the middle years. With the introduction of standards at state and national levels in these years, teacher judgement as developed in moderation practices is now vital. This paper argues, that in this context of assessment reform, standards intended to inform teacher judgement and to build assessment capacity are necessary but not sufficient for maintaining teacher and public confidence in schooling. Teacher judgement is intrinsic to moderation, and to professional practice, and can no longer remain private. Moderation too is intrinsic to efforts by the profession to realise judgements that are defensible, dependable and open to scrutiny. Moderation can no longer be considered an optional extra and requires system-level support especially if, as intended, the standards are linked to system-wide efforts to improve student learning. In presenting this argument we draw on an Australian Research Council funded study with key industry partners (the Queensland Studies Authority and the National Council for Curriculum and Assessment of the Republic of Ireland). The data analysed included teacher interview data and additional teacher talk during moderation sessions. These were undertaken during the initial phase of policy development. The analysis identified those issues that emerge in moderation meetings that are designed to reach consistent, reliable judgements. Of interest are the different ways in which teachers talked through and interacted with one another to reach agreement about the quality of student work in the application of standards. There is evidence of differences in the way that teachers made compensations and trade-offs in their award of grades, dependent on the subject domain in which they teach. This article concludes with some empirically derived insights into moderation practices as policy and social events.

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Hong Kong is a modern global city with a reputation for well-regulated financial markets, but for years, the government had been trying to enact laws on corporate rescue procedures with relatively little success. It is under the pretext of the Global Financial Crisis, the threat of a future economic meltdown gave the Hong Kong government the impetus to revisit this issue. This third attempt to codify statutory obligations on directorsâ liability for insolvent trading has been criticised for either setting the standards too high or low for directors trading whilst insolvent. There is also some reservation given the beliefs and values of directors in Chinese family-owned and controlled companies. These companies would most likely trade out the difficult times. Nevertheless, this does not negate from the fact that the enactment of corporate rescue procedures in Hong Kong in 2010 is a momentous achievement for the Hong Kong government.

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Objective--To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). Design and setting--A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital.Main outcome measures-- Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival.Results--Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Conclusions--Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.

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Being in paid employment is socially valued, and is linked to health, financial security and time use. Issues arising from a lack of occupational choice and control, and from diminished role partnerships are particularly problematic in the lives of people with an intellectual disability. Informal support networks are shown to influence work opportunities for people without disabilities, but their impact on the work experiences of people with disability has not been thoroughly explored. The experience of 'work' and preparation for work was explored with a group of four people with an intellectual disability (the participants) and the key members of their informal support networks (network members) in New South Wales, Australia. Network members and participants were interviewed and participant observations of work and other activities were undertaken. Data analysis included open, conceptual and thematic coding. Data analysis software assisted in managing the large datasets across multiple team members. The insight and actions of network members created and sustained the employment and support opportunities that effectively matched the needs and interests of the participants. Recommendations for future research are outlined.

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In their correspondence, He and colleagues question our conclusion of little or no uplift preceding Emeishan volcanism that we reported in our letter1. Debate concerns the nature of the contact between the Maokou limestone and Emeishan volcanics, the depositional environment and volumetric significance of mafic hydromagmatic deposits (MHDs), and evidence for symmetrical domal thinning. MHDs in the Daqiao section are separated from the Maokou limestone by 100 m of subaerial basaltic lavas, but elsewhere MHDs â previously interpreted as basal conglomerates2, 3 â directly overlie the Maokou2, 3. MHDs thus feature strongly in basal sections of the Emeishan lava succession, as also recently shown4 elsewhere in the Emeishan. An irregular surface at the top of the Maokou limestone has been interpreted as an erosional unconformity2, 3, but clastic deposits presented as evidence of this erosion2, 3 are MHDs produced by explosive magmaâwater interaction1. A clear demonstration that this irregular top surface is an erosional truncation of limestone reef facies (slope/rim, flat, lagoonal) is currently lacking, but is critical because reefs and carbonate platforms show considerable natural relief of tens of metres. The persistent hot, wet climate since the Oligocene has produced well-developed weathering profiles on exposed Palaeozoic marine sedimentary sequences5, but weathering and karst relief of the uppermost Maokou limestone underlying the flood basalts have not been properly documented, nor shown to be of middle Permian age and immediately preceding emplacement of the large igneous province.

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A series of porphyrins substituted in one or two meso-positions by diphenylphosphine oxide groups has been prepared by the palladium catalysed reaction of diphenylphosphine or its oxide with the corresponding bromoporphyrins. Compounds {MDPP-[P(O)Ph2]n} (M = H2, Ni, Zn; H2DPP = 5,15-diphenylporphyrin; n = 1, 2) were isolated in yields of 60-95%. The reaction is believed to proceed via the conventional oxidative addition, phosphination and reductive elimination steps, as the stoichiometric reaction of η1-palladio(II) porphyrin [PdBr(H2DPP)(dppe)] (H2DPP = 5,15-diphenylporphyrin; dppe = 1,2-bis(diphenylphosphino)ethane) with diphenylphosphine oxide also results in the desired mono-porphyrinylphosphine oxide [H2DPP-P(O)Ph2]. Attempts to isolate the tertiary phosphines failed due to their extreme air-sensitivity. Variable temperature 1H NMR studies of [H2DPP-P(O)Ph2] revealed an intrinsic lack of symmetry, while fluorescence spectroscopy showed that the phosphine oxide group does not behave as a "heavy atom" quencher. The electron withdrawing effect of the phosphine oxide group was confirmed by voltammetry. The ligands were characterised by multinuclear NMR and UV-visible spectroscopy as well as mass spectrometry. Single crystal X-ray crystallography showed that the bis(phosphine oxide) nickel(II) complex {[NiDPP-[P(O)Ph2]2} is monomeric in the solid state, with a ruffled porphyrin core and the two P=O fragments on the same side of the average plane of the molecule. On the other hand, the corresponding zinc(II) complex formed infinite chains through coordination of one Ph2PO substituent to the neighbouring zinc porphyrin through an almost linear P=O---Zn unit, leaving the other Ph2PO group facing into a parallel channel filled with disordered water molecules. These new phosphine oxides are attractive ligands for supramolecular porphyrin chemistry.

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ABSTRACT Twelve beam-to-column connections between cold-formed steel sections consisting of three beam depths and four connection types were tested in isolation to investigate their behavior based on strength, stiffness and ductility. Resulting moment-rotation curves indicate that the tested connections are efficient moment connections where moment capacities ranged from about 65% to 100% of the connected beam capac-ity. With a moment capacity of greater than 80% of connected beam member capacity, some of the connec-tions can be regarded as full strength connections. Connections also possessed sufficient ductility with rota-tions of 20 mRad at failure although some connections were too ductile with rotations in excess of 30 mRad. Generally, most of the connections possess the strength and ductility to be considered as partial strength con-nections. The ultimate failures of almost all of the connections were due to local buckling of the compression web and flange elements of the beam closest to the connection.

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This paper presents the details of experimental studies on the shear strength of a recently developed, cold-formed steel beam known as LiteSteel Beam (LSB) with web openings. The innovative LSB sections have the beneficial characteristics of torsionally rigid closed rectangular flanges combined with economical fabrication processes from a single strip of high strength steel. They combine the stability of hot-rolled steel sections with the high strength to weight ratio of conventional cold-formed steel sections. The LSB sections are commonly used as flexural members in the building industry. Current practice in flooring systems is to include openings in the web element of floor joists or bearers so that building services can be located within them. Shear behaviour of LSBs with web openings is more complicated while their shear strengths are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LSBs with web openings. Therefore a detailed experimental study involving 26 shear tests was undertaken to investigate the shear behaviour and strength of different LSB sections. Simply supported test specimens of LSBs with an aspect ratio of 1.5 were loaded at midspan until failure. This paper presents the details of this experimental study and the results. Experimental results showed that the current design rules in cold-formed steel structures design codes (AS/NZS 4600) [1] are very conservative for the shear design of LSBs with web openings. Improved design equations have been proposed for the shear strength of LSBs with web openings based on experimental results from this study.