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The most common presentation of nonsyndromic craniosynostosis is that of the sagittal suture. Amongst this subgroup there is a significant male preponderance. Although the etiology is largely unknown, androgen exposure in utero has been suggested as a contributing factor. The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic trait, reflective of the levels of androgen and estrogen exposure in utero, with a lower 2D:4D ratio associated with higher androgen exposure.This study aimed to examine the difference in 2D:4D ratio between participants with sagittal synostosis (SS) and gender- matched controls, hypothesizing that alterations in androgen exposure would be reflected in participants' 2D:4D ratio.Participants with nonsyndromic SS and gender-matched controls were prospectively recruited from outpatients clinics. Photographs were taken of the right hand, and 3 independent researchers measured the length of the fingers and 2D:4D ratio, with the mean 2D:4D ratio then calculated.Fifty-six participants were recruited to both groups, with 35 males and 21 females in each. The mean age of the study and control groups were 5.6 and 6.3 years, respectively. There was no difference in the 2D:4D ratio between groups overall ( P = 0.126). However, males with SS had a significantly higher 2D:4D ratio in comparison to male controls (0.969 ± 0.379 versus 0.950 ± 0.354, P = 0.038).Our results suggest that 1 single hormonal pathway is not responsible for suture fusion. Subsequently we consider that an imbalance between testosterone and estrogen signaling may contribute to the development of sagittal craniosynostosis.

Sagittal synostosis (SS) is the commonest form of craniosynostosis. Children with sagittal synostosis in Ireland are treated in the National Paediatric Craniofacial Centre (NPCC) in Temple Street Children's University Hospital. This retrospective study analysed the correlation between referral patterns to the unit and age at operation. The notes of 81 patients referred over a 5-year period (April 2008 - April 2013) to the NPCC with non-syndromic SS were reviewed and demographics and referral information were recorded. Of 81 patients reviewed, 60 (74%) were referred before 6 months of age, while 21 (26%) had late referrals. Neonatologists referred 100% of infants before 6 months, paediatricians referred 71%, and GPs 64%. Later referral was associated with a more complex referral pathway, including multiple-steps of referral and unnecessary investigations. Improved clinician knowledge and emphasis on the importance of early referral may lead to a reduction in late referrals.

Cranial fasciitis is an exceedingly rare, benign, fibroblastic tumour of the skull of young children. It was first described in 1980 by Lauer and Enzinger as a subset of nodular fasciitis. There are fewer than 55 cases described in the literature.We describe the presentation of a 2-year-old girl with a rapidly growing left temporal lesion, initially treated as an intramuscular haemangioma with propanolol. Following failure of response to this management, radiological and histological investigations indicated cranial fasciitis, and multidisciplinary surgery was undertaken via a bicoronal incision. Gross total resection was carried out, and the lesion was found to be adherent to but not infiltrating the dura. The petrous bone and zygomatic arch appeared destroyed, leaving a large temporal bony defect. This was repaired with a split calvarial graft from the outer table of the right parietal bone.Histology confirmed a diagnosis of cranial fasciitis. She had an uneventful post-operative course and was discharged home well. A CT scan 8 months post-operatively showed no residual lesion and it was noted that the reconstruction had fully integrated and the zygomatic arch had reformed.

External validation is an integral part of the process of simulation model development. Many methods of external validation of continuous system simulation models have been proposed and, inevitably, the approach selected in any given application is highly dependent upon the purpose of the model and the associated accuracy requirements. Although the process of external validation has subjective aspects, formalisation of methods in some safety-critical fields of application has provided a basis for the development of objective measures of model performance. Such measures can be applied in other application areas and allow the whole process of assessing model credibility to be put on a firmer foundation. This paper reviews available methods, discusses practical issues that can arise in the application of these validation techniques and gives a brief account of some validation problems in selected application areas.

A distributed real-time system for monitoring and characterizing the underwater soundscape is presented in the context of environmental impact baseline assessment for the ocean energy industry. We discuss the development and deployment of an offshore acoustic monitoring buoy with real-time acoustic signal transmission capabilities and an accompanying sea floor-based sensor platform utilizing hydrophone and particle velocity detector technologies. In addition, high bandwidth point-to-point communications for the buoy to shore communications and data streaming architectures with failover protection in a high speed networking environment are described. An integrated stream analytical processing platform has been developed for the real-time signal processing of multiple high bandwidth acoustic data streams in parallel that incorporates multiple preprocessing steps as well as event detection and classification techniques. Real-time dynamic filtering approaches are also being developed using supplemental data such as sea state and weather to compensate for varying environmental conditions. These technologies are being incorporated in the Marine Institute of Ireland's multipurpose research and development SmartBay Ireland system, which provides a flexible and agile monitoring and management platform that is being extended to include additional environmental variables relevant to the ocean energy domain. The platform is deployed for the Galway Bay Quarter Scale Wave Energy Test Site and will capture, store, and analyze one year of continuous acoustic data.

[1] This paper presents remotely sensed neutral temperatures obtained from ultraviolet observations and compares them with temperatures from the NRLMSISE-00 version of the Mass Spectrometer and Incoherent Scatter (MSIS) model (unconstrained and constrained to match the total densities from satellite drag). Latitudinal profiles of the temperatures in the Earth's thermosphere are obtained by inversion of high-resolution (∼1.3 A) observations of the (1,1) and (5,4) Lyman-Birge-Hopfield (LBH) bands of N2. The spectra are from the High resolution Ionospheric and Thermospheric Spectrograph (HITS) instrument aboard the Advanced Research and Global Observation Satellite (ARGOS). The results indicate that on each day examined there was consistency between the remotely sensed thermospheric temperatures, the densities from coincident satellite drag measurements at adjacent altitudes, and the NRLMSISE-00 model.

Anesthesiology as a specialty has made numerous prescient commitments to better patient care. Physicians entering residency are reaching the zenith of their educational odyssey and primarily acquire knowledge and skill through active involvement. Simulation training and associated assessment offers a chance for active involvement to the learner. The goal of the training is to accelerate skill acquisition, improve skill retention and reduce the extinction of skills. Simulation training programs have been shown to increase the skill of anesthesiologists. This increase in skill is expected to translate to evidence of improved patient care. Direct evidence that simulation directly improves patient care continues to be difficult to establish. In the future, the intuitive benefit of simulation as a means to improve the safety and quality of patient care is likely to become established by clinical research.

The purpose of this paper is to review the indications for transrectal ultrasound; to briefly describe the sonographic technique; to describe the sonographic findings of prostatic carcinoma; to review the indications for transrectal sonographic-guided biopsy; and to discuss the controversles of routine screening and staging.

The second annual meeting of the North Atlantic Treaty Organization’s (NATO) Committee on the Challenges to Modern Society (CCMS) pilot study on Clean Products and Processes was held in Belfast, Northern Ireland on March 21–25, 1999. The meeting was hosted by Queen’s University, Belfast and Professor Jim Swindall, Director of Queen’s University Environmental Science and Technology Research (QUESTOR) Center. The meeting included participants from Bulgaria, Canada, the Czech Republic, Denmark, Germany, Hungary, Israel, Italy, Japan, Lithuania, Poland, Portugal, Romania, the Slovak Republic, Turkey, the Ukraine, the United Kingdom, and the United States. Four types of activities and presentations took place at the meeting to promote the sharing of technical information and interaction among delegates. These included Tour de Table presentations by each national delegate. The delegates provided overviews of applications and research on clean product and processes in their countries. Also, Pilot Project Updates were given to share information on the status of each of the following pilot projects selected during the first year of the pilot study: I Danish Product Oriented Environmental Measures in the Textile Industry (Denmark) I Pollution Prevention Tools (United States) I Energy Efficiency in Moldova (Moldova) I Water Conservation and Recycling in Semiconductor Industry: Control of Organic Contamination and Biofouling in Ultra Pure Water Systems (United Kingdom and United States) I Conducting Research and Development Aimed at Developing Cleaner Production Technologies to Assist Textile Industry to Manufacture in Compliance with International Standards (Turkey) I Cleaner Production through the Use of Intelligent Systems in the Pulp and Paper Industry (Canada) I Pollution Prevention Development and Utilization – A History to 2000 (United States) I Cleaner Energy Production with Combined Systems (Turkey)

Abnormal labial frena are capable of retracting gingival margins, creating diastemas, and limiting lip movement. When these frena are present, the traditional frenectomy alone generally is successful. However, when the frenulum is extensive, the possibility of coronal reformation exists. Several procedures have combined the frenectomy with either a lateral pedicle flap, free papilla graft, or free gingival (mucosal) graft taken from the palate. Three case reports demonstrate the continued efficacy of the traditional palatal free gingival graft when the patient has an extensive frenulum or an area of minimal esthetic concern is involved.

Single-stage laryngotracheoplasty (SSLTP) provides a method of correcting mild-to-moderate laryngotracheal stenosis while avoiding the risks of prolonged laryngeal sten ting. Pediatric patients are orally intubated for 5 to 7 days postoperatively to ensure an adequate airway while edema resolves and healing begins. During this period, continuous neuromuscular blockade has been advocated in infants and young children to avoid endotracheal tube trauma to the fresh graft and potentially life-threatening accidental decannulation. Pulmonary atelectasis is the most common morbidity associated with prolonged neuromuscular blockade. Neuromuscular weakness also may follow prolonged paralysis and prolong hospitalization. This paper compares the postoperative course of 17 patients who underwent 18 SSLTP procedures by the senior author. The first 8 patients received continuous neuromuscular blockade in the early postoperative period. To reduce perceived morbidity, the last 9 patients were managed with a protocol that incorporated daily 4- to 8-hour “interruptions” of paralysis. Seven patients tolerated this protocol modification. As a group, these patients had less postoperative pulmonary atelectasis prior to extubation (p < .05) and were extubated sooner than patients receiving continuous neuromuscular blockade (p < .05) without compromising the surgical success of the procedure. Intermittent paralysis permitted for more accurate assessment of pain control and protected against accidental drug accumulation. Although self-extubation did not occur, diligent nursing care with adequate sedation and analgesia is necessary to avoid the risk of accidental extubation.

Skeletal muscles are highly complex active nonlinear systems in which chemical energy is converted into mechanical energy. These muscles, which are associated with body movement, can exert active force by contraction and they are normally organized in functional pairs or groups to allow bidirectional motion about a joint.

The programming of mathematical expressions and the implementation of numerical methods, such as those reviewed in Chapters 4 and 5, can be facilitated by the use of general-purpose scientific programming languages, such as Fortran. Libraries of specialized subprograms can be called by the programmer when required. Such programming aids can save considerable amounts of program development time and, when correctly used, can avoid the introduction of many programming errors. In some cases routines for the solution of ordinary differential equations have been brought together as a ‘package’ which allows the programmer to use a general-purpose high-level language to create a special-purpose simulation program. This is similar in principle to the use of a more general library of numerical routines, but the package may incorporate specialized features of special relevance to simulation developers. A further type of programming aid has also been developed which can allow the programmer to formulate the problem in a more direct form than is possible using a general-purpose high-level language. This takes the form of a problem-oriented language, or support language, which contains specialized features of value only for the specialized computational tasks involved in a particular type of application. Continuous system simulation languages form one important class of problem-oriented language.

The only form of interactive man-machine interface which was generally available until the 1970s involved the user entering commands via a keyboard. These commands were then interpreted and acted upon by the operating system or program. Such an interface makes it necessary for the user to learn a command language, and it is claimed that this may introduce a significant psychological barrier for some people. Since the command language is different for different operating systems, in terms of both syntax and the facilities available, it can certainly be time-consuming and frustrating to have to make a change from one system to another.

In discussing continuous system simulation languages in Chapter 6 it was pointed out that the only widely accepted’ standard’ which exists for continuous system simulation software is the CSSL specification published in 1967. Many important developments since that time have been based on the 1967 specification, but it is now recognized that software engineering principles, and other developments in hardware and software, provide opportunities for some entirely new concepts in simulation languages. New languages are already in use, such as ESL [1], COSMOS [21 and SYSMOD [3], which are in some respects fundamentally different from previous generations of simulation software and were developed using software engineering principles. The ESL simulation language, which was developed at the University of Salford in the UK with support from the European Space Agency (ESA), is of particular interest. It was based upon outline proposals produced at Salford in 1981 for a new CSSL specification [41. The ideas contained in that software specification did not define a complete simulation language and were intended to provoke discussion within the simulation community. The proposals by the Salford group were an outline and allowed flexibility and potential for contributions by others by leaving many points of detail unspecified. Although discussed at considerable length by the CSSL Committee of the Society for Computer Simulation (SCS), and by the Technical Committee TC3 of the International Association for Mathematics and Computers in Simulation (IMACS), no formal specification emerged. Many of the developments in simulation software which have taken place since 1981 are consistent with the ideas which were put forward in that outline specification.

Much scientific and engineering work involves the formalization of knowledge and the building of models. From experiments and observations one can form abstract representations and laws which can then provide a basis for analysis or engineering design. Mathematical models are one particular type of abstract representation which has been found to provide a very effective means of encoding information about a real system. Such representations can also serve to compress large amounts of observational data and allow quantitative relationships to be established which may not be directly evident from experimental data.

Mathematical modeling and computer simulation techniques are being used increasingly in the field of respiratory physiology and medicine. Aspects of the respiratory system to which simulation methods have been applied include, for example, the study of lung mechanics and gas flow in the airways, the investigation of gas-exchange phenomena and the highly complex physiological processes involved in the control of breathing. The objectives, as in many other areas of physiology, may include advancing physiological and clinical knowledge through the development of validated quantitative descriptions, or the development of methods for the indirect estimation of physiological quantities such as airway resistance, or the development of aids for training and education.

Careful organization of the information available regarding a system and any associated mathematical models is of great importance as a first step in the development of a simulation. This information must include a statement concerning the intended application of the simulation and the reasons for undertaking the investigation. The data to be used in establishing values of constants in the simulation model must be thoroughly assessed since the value of the simulation will be highly dependent on the error bounds and other uncertainties associated with the numerical values of these quantities. There is little point in obtaining simulation results to a very high degree of accuracy if the parameters of the underlying model are known only to within 20% or 30%. Careful assessment of the source data in this way also ensures that any omissions or inconsistencies are spotted at an early stage, thus allowing steps to be taken to obtain further data if necessary, without delaying the development of the computer implementation.

CD38 is a transmembrane glycoprotein expressed in many cell types, including lymphoid progenitors and activated lymphocytes. High levels of CD38 expression on immature lymphoid cells suggest its role in the regulation of cell growth and differentiation, but there is no evidence demonstrating a functional activity of CD38 on these cells. We used stroma-supported cultures of B cell progenitors and anti-CD38 monoclonal antibodies (T16 and IB4) to study CD38 function. In cultures of normal bone marrow CD19+ cells (n = 5), addition of anti-CD38 markedly reduced the number of cells recovered after 7 d. Cell loss was greatest among CD19+ sIg- B cell progenitors (mean cell recovery +/- SD = 7.2 +/- 11.7% of recovery in control cultures) and extended to CD19+CD34+ B cells (the most immature subset; 7.6 +/- 2.2%). In contrast, CD38 ligation did not substantially affect cell numbers in cultures of normal peripheral blood or tonsillar B cells. In stroma-supported cultures of 22 B-lineage acute lymphoblastic leukemia cases, anti-CD38 suppressed recovery of CD19+ sIg- leukemic cells. CD38 ligation also suppressed the growth of immature lymphoid cell lines cultured on stroma and, in some cases, in the presence of stroma-derived cytokines (interleukin [IL] 7, IL-3, and/or stem cell factor), but did not inhibit growth in stroma- or cytokine-free cultures. DNA content and DNA fragmentation studies showed that CD38 ligation of stroma-supported cells resulted in both inhibition of DNA synthesis and induction of apoptosis. It is known that CD38 catalyzes nicotinamide adenine dinucleotide (NAD+) hydrolysis into cyclic ADP-ribose (cADPR) and ADPR. However, no changes in NAD+ hydrolysis or cADPR and ADPR production after CD38 ligation were found by high-performance liquid chromatography; addition of NAD+, ADPR, or cADPR to cultures of lymphoid progenitors did not offset the inhibitory effects of anti-CD38. Thus, anti-CD38 does not suppress B lymphopoiesis by altering the enzymatic function of the molecule. In conclusion, these data show that CD38 ligation inhibits the growth of immature B lymphoid cells in the bone marrow microenvironment, and suggest that CD38 interaction with a putative ligand represents a novel regulatory mechanism of B lymphopoiesis.

The design, development and testing of many engineering systems, such as aircraft and their flight-control systems, missiles, ship-propulsion systems, road vehicle suspension systems and certain kinds of chemical plant, can benefit, at certain stages of the process, from the use of computer simulation models which operate in the same timescale as the real system so that the execution time of the model is matched to the real system time. This is generally known as ‘real-time’ simulation. It is particularly important in applications in which the simulation may have to run with a human operator as part of a closed-loop system or in conjunction with real engineering hardware. Simulation may then be used to check interactions between individual items of equipment and to investigate the total system operation.

Difference equations are easy to program in comparison with differential equations. Although they are normally associated with models of entirely discrete systems, with sampled-data systems or with digital control systems which are partly continuous and partly discrete, difference equations can also be used in the simulation of continuous systems.

This chapter provides examples of a number of different types of simulation problem. The models upon which the simulations are based are relatively simple, and have been chosen to illustrate features of some typical simulation tools which are currently available and the application of the principles introduced in Chapters 3, 4, 5 and 6. Particular techniques have been selected, but this choice is not intended to suggest that other tools could not have provided an equally appropriate solution. Strengths and weaknesses of some methods of approach are discussed. In each case suggestions of further investigations which could be made with these simple models are outlined.

Systems involving tanks containing liquid are found in many industrial situations. Examples include blending and reaction vessels in chemical processes and boiler systems in electrical power stations. The design of automatic control systems for the regulation of liquid level is thus of considerable practical importance and requires an appropriate mathematical model of the plant (the system to be controlled) as a starting point. This chapter is concerned with the modeling of hydraulic systems of this kind and with discussion of methods for the verification and validation of a simulation model of a laboratory-scale system involving two interconnected vessels.

The solution of a differential equation can be obtained by mathematical operations which involve integration. In order to obtain a solution using a digital computer the analytic processes of integration must be replaced by a numerical method which can yield an approximation to the true solution. A continuous variable x which is a function of the independent variable t (i.e. time) is represented within a digital simulation by a series of numbers, or samples, x 0, x 1, x 2,…, x n . These samples define the variable x in terms both of magnitude and sign at the times t 0, t 1, t 2,…, t n . For many purposes it may be assumed that these samples are equally spaced in time and it is clear that if the sampling rate is high the information loss owing to sampling can be small. However, the step size, h, does affect the size of the error in the numerical approximation and the choice of h must depend upon the dynamic characteristics of the system under consideration.

Expanding metal stents were used to treat symptomatic pancreatic duct obstruction in two patients with chronic pancreatitis. Both patients initially underwent percutaneous external pancreatic duct drainage and then had metal stents inserted for internal drainage. Both patients remained asymptomatic, and the stents were patent during short-term follow-up periods of 6 and 9 months, respectively. Percutaneous insertion of metal stents, which can be performed to treat pancreatic duct obstruction after a trial of external drainage has been shown to relieve the patient's symptoms, should be considered as an alternative to endoscopic stent placement or surgical drainage.

An audiologic rationale for the application of digital signal processing techniques to hearing aids is developed. These techniques enable complex processing beyond that possible in presently available analog aids. A critical survey of algorithms for filtering, nonlinear processing, noise reduction, speech enhancement, and feedback reduction is presented. The paper concludes with a discussion of practical considerations for implementation.

A prospective study was undertaken to determine the change in coagulation factors in patients undergoing tangential excisions of burn wounds when red blood cells preserved with ADSOL (adenine, dextrose, saline, and mannitol) and crystalloid solution were used for volume replacement. Nine patients with burns were studied, three on two separate occasions. No patient had a history of a bleeding disorder or had taken aspirin within 10 days of surgery. Results of preoperative coagulation studies were all within normal limits. The initial levels of coagulation factor and rates of removal were compared with those of 12 patients without burns who were undergoing elective surgery and who also had massive intraoperative blood loss. Coagulation factor levels measured included the platelet count, fibrinogen, factors V, VIII, and IX. These were determined before blood loss and each time loss and replacement of one third of a patient's calculated blood volume occurred during a tangential excision of a burn wound. The data showed that patients with burns have significantly higher baseline levels of platelets, fibrinogen, and factor VIII than patients without burns do. The removal rates of platelet and factor IX are significantly lower among patients with burns than among patients without burns. No patient in the study group developed a coagulopathy or received fresh frozen plasma or platelet supplementation. These findings suggest that the intraoperative blood losses that occurred during tangential excisions of burn wounds were made safe by the higher than normal preoperative levels of platelets, fibrinogen, and factor VIII and by the slow wash-out curve for platelets and factor IX. Prophylactic use of either fresh frozen plasma or platelet concentrates is not indicated unless a specific deficit or coagulopathy has been identified.