Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment

BACKGROUND: Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. STUDY DESIGN: We investigated the impact of imple- menting a protocol aiming at reducing the number of dia- gnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. RESULTS: Among the 11,503 infants born at 35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving an- tibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of dia- gnostic tests was associated with earlier antibiotic treat- ment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. CONCLUSION: Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treat- ment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

The Role of the Delay Time in the Modeling of Biological Range Expansions

The time interval between successive migrations of biological species causes a delay time in the reaction-diffusion equations describing their space-time dynamics. This lowers the predicted speed of the waves of advance, as compared to classical models. It has been shown that this delay-time effect improves the modeling of human range expansions. Here, we demonstrate that it can also be important for other species. We present two new examples where the predictions of the time-delayed and the classical (Fisher) approaches are compared to experimental data. No free or adjustable parameters are used. We show that the importance of the delay effect depends on the dimensionless product of the initial growth rate and the delay time. We argue that the delay effect should be taken into account in the modeling of range expansions for biological species

Delay reduction in courts of justice – possibilities and challenges of process improvement in professional public organizations

Delays in the justice system have been undermining the functioning and performance of the court system all over the world for decades. Despite the widespread concern about delays, the solutions have not kept up with the growth of the problem. The delay problem existing in the justice courts processes is a good example of the growing need and pressure in professional public organizations to start improving their business process performance.This study analyses the possibilities and challenges of process improvement in professional public organizations. The study is based on experiences gained in two longitudinal action research improvement projects conducted in two separate Finnish law instances; in the Helsinki Court of Appeal and in the Insurance Court. The thesis has two objectives. First objective is to study what kinds of factors in court system operations cause delays and unmanageable backlogs and how to reduce and prevent delays. Based on the lessons learned from the case projects the objective is to give new insights on the critical factors of process improvement conducted in professional public organizations. Four main areas and factors behind the delay problem is identified: 1) goal setting and performance measurement practices, 2) the process control system, 3) production and capacity planning procedures, and 4) process roles and responsibilities. The appropriate improvement solutions include tools to enhance project planning and scheduling and monitoring the agreed time-frames for different phases of the handling process and pending inventory. The study introduces the identified critical factors in different phases of process improvement work carried out in professional public organizations, the ways the critical factors can be incorporated to the different stages of the projects, and discusses the role of external facilitator in assisting process improvement work and in enhancing ownership towards the solutions and improvement. The study highlights the need to concentrate on the critical factors aiming to get the employees to challenge their existing ways of conducting work, analyze their own processes, and create procedures for diffusing the process improvement culture instead of merely concentrating of finding tools, techniques, and solutions appropriate for applications from the manufacturing sector

Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Control of Structures with Cubic and Quadratic Non-Linearities with Time Delay Consideration

This paper studies the effect of time delay on the active non-linear control of dynamically loaded flexible structures. The behavior of non-linear systems under state feedback control, considering a fixed time delay for the control force, is investigated. A control method based on non-linear optimal control, using a tensorial formulation and state feedback control is used. The state equations and the control forces are expressed in polynomial form and a performance index, quadratic in both state vector and control forces, is used. General polynomial representations of the non-linear control law are obtained and implemented for control algorithms up to the fifth order. This methodology is applied to systems with quadratic and cubic non-linearities. Strongly non-linear systems are tested and the effectiveness of the control system including a delay for the application of control forces is discussed. Numerical results indicate that the adopted control algorithm can be efficient for non-linear systems, chiefly in the presence of strong non-linearities but increasing time delay reduces the efficiency of the control system. Numerical results emphasize the importance of considering time delay in the project of active structural control systems.

Families with Children with Autism, Developmental Delay, and Typical Development: The Relationships of Parenting Self-Efficacy, Parenting Strategies, and Child Problem Behaviour

Parents of children with autism spectrum disorders (ASD) and developmental delays (DD) may experience more child problem behaviours, report lower parenting selfefficacy (PSE), and be more reactive than proactive in their parenting strategies than those who have children with typical development (TD). Differences in PSE and parenting strategies may also influence the extent to which child problem behaviours are experienced by parents who have children with ASD and DD, compared to those who have children with TD. Using a convenience sample of parents of children with ASD (n = 48), DD (n = 51), and TD (n = 72), this study examined group differences on three key variables: PSE, parenting strategies, and child problem behaviour. Results indicated that those in the DD group scored lower on PSE in preventing child problem behaviour than the ASD group. The TD group used fewer reactive strategies than the DD group, and fewer proactive strategies than both the ASD and DD groups. For the overall sample, higher reactive strategies use was found to predict higher ratings of child problem behaviour, while a greater proportion of proactive to reactive strategies use predicted lower ratings of child problem behaviour. PSE was found to moderate DD diagnosis and child problem behaviour. Implications for a behavioural (i.e., parenting strategies) or cognitive (i.e., PSE) approach to parenting are discussed.

Automated synthesis of delay-reduced Reed-Muller universal logic module networks

This paper presents a new approach to implement Reed-Muller Universal Logic Module (RM-ULM) networks with reduced delay and hardware for synthesizing logic functions given in Reed-Muller (RM) form. Replication of single control line RM-ULM is used as the only design unit for defining any logic function. An algorithm is proposed that does exhaustive branching to reduce the number of levels and modules required to implement any logic function in RM form. This approach attains a reduction in delay, and power over other implementations of functions having large number of variables.

The effects of a pre-movement delay on the kinematics of prehension in middle childhood

The present study examined the effects of a pre-movement delay on the kinematics of prehension in middle childhood. Twenty-five children between the ages of 5 and 11 years made visually open-loop reaches to two different sized objects at two different distances along the midline. Reaches took place either (i) immediately, or (ii) 2 s after the occlusion of the stimulus. In all age groups, reaches following the pre-movement delay were characterised by longer movement durations, lower peak velocities, larger peak grip apertures and longer time spent in the final slow phase of the movement. This pattern of results suggests that the representations that control the transport and grasp component are affected similarly by delay, and is consistent with the results previously reported for adults. Such representations therefore appear to develop before the age of 5. (C) 2004 Elsevier B.V. All rights reserved.

An on-line algorithm of uncertain time delay estimation in a continuous system

In this paper, we present an on-line estimation algorithm for an uncertain time delay in a continuous system based on the observational input-output data, subject to observational noise. The first order Pade approximation is used to approximate the time delay. At each time step, the algorithm combines the well known Kalman filter algorithm and the recursive instrumental variable least squares (RIVLS) algorithm in cascade form. The instrumental variable least squares algorithm is used in order to achieve the consistency of the delay parameter estimate, since an error-in-the-variable model is involved. An illustrative example is utilized to demonstrate the efficacy of the proposed approach.