Noticeable Problems Research Articles

Applications of population pharmacokinetics in current drug labelling

The application of population pharmacokinetics (PopPK) appears increasingly in drug labelling. The current study was to examine the use of PopPK in dose recommendation in drug-product labels. PopPK information was identified in the data sheets included in the physician desk reference (PDR). Electronic key word searches were conducted in the electronic library of PDR. The use of PopPK in the prescribing information, including the determination of dosing regimen, dosing in special populations and dose-adjustments was summarized and evaluated. The reliability and criteria for integrating the information derived from PopPK studies into the product labelling were discussed. Among more than 2500 items listed in the PDR, 88 listings were found to have PopPK information in the labelling. The information included general data (Gen) on pharmacokinetics (PK) and the effects of gender (sex), age, race, drug-drug interactions (DDI), smoking (Smk), alcohol consumption (Alc), disease state (Dis), renal impairment (Ren) and metabolic status (Met) on the PK parameters (Table). Whether there was an effect (+) or not (-) is also shown. Appendix 1 lists the products included in each category. Searches conducted at different times suggest an increase in both quantity and quality of PopPK data in drug development. PopPK is widely used in paediatric studies and the sample sizes in these studies are sometimes too small. The application of PopPK to protein drugs is increasing rapidly (Appendix 2). Several precautions should be exercised when PopPK is applied to protein drugs. When considering gender effects, different normalization methods for body weight have been used. The number of subjects included in the PopPK analysis should be given and the influence of the imbalance in any covariate should be investigated. PopPK-DDI results are particularly difficult to evaluate unless details about potentially influential factors such as dosing and sampling information for both drug and interacting drugs are given. The use of PopPK to aid optimal dosing is increasing. Several noticeable problems raised usually avoid the acceptability of PopPK studies. More investigations are needed to inform the development of consensuses on these issues. There is an accelerating shift from PopPK to PopPK/PD. The limitations of such modelling should be recognized.

Hydrodynamic interaction in polymer solutions simulated with dissipative particle dynamics

The authors analyzed extensively the dynamics of polymer chains in solutions simulated with dissipative particle dynamics (DPD), with a special focus on the potential influence of a low Schmidt number of a typical DPD fluid on the simulated polymer dynamics. It has been argued that a low Schmidt number in a DPD fluid can lead to underdevelopment of the hydrodynamic interaction in polymer solutions. The authors' analyses reveal that equilibrium polymer dynamics in dilute solution, under typical DPD simulation conditions, obey the Zimm [J. Chem. Phys. 24, 269 (1956)] model very well. With a further reduction in the Schmidt number, a deviation from the Zimm model to the Rouse model is observed. This implies that the hydrodynamic interaction between monomers is reasonably developed under typical conditions of a DPD simulation. Only when the Schmidt number is further reduced, the hydrodynamic interaction within the chains becomes underdeveloped. The screening of the hydrodynamic interaction and the excluded volume interaction as the polymer volume fraction is increased are well reproduced by the DPD simulations. The use of soft interaction between polymer beads and a low Schmidt number do not produce noticeable problems for the simulated dynamics at high concentrations, except for the entanglement effect which is not captured in the simulations.

On pancreatoduodenectomy in combination with vascular resection

目的 探讨联合血管切除的胰十二指肠切除术的必要性、手术适应证和手术操作中必须注意的问题.方法 回顾性分析我院2002年1月至2005年1月行联合血管切除的胰十二指肠病人43例(A组),并与同期未行联合血管切除的96例病人(B组)在术中、术后各方面进行比较.结果 A组中单独PV或SMV节段切除者为8和16例,楔形切除分别为3和4例,同时切除PV/SMV者9例,联合PV/SMV/SMA/HA切除者3例;A组病理示肿瘤侵犯血管全层共6例(13.95%);A、B两组在术时、术中输血量及术后并发症、淋巴结阳性率方面差异均无显著性.结论 对术前检查未发现PV/SMV内有癌栓或闭塞、肿瘤未包埋SMA或腹腔干根部的病人,行联合血管切除的胰十二指肠切除术是必要的,但须严格掌握手术适应证且术中解剖仔细、操作细致,以期提高手术的安全性和成功率。

Prosody and voice characteristics of children with cochlear implants

This descriptive, longitudinal study involved the analysis of the prosody and voice characteristics of conversational speech produced by six young children with severe to profound hearing impairments who had been fitted with cochlear implants. A total of 40 samples were analyzed using the Prosody–Voice Screening Profile (PVSP; Shriberg, L. D., Kwiatkowski, J., & Rasmussen, C. (1990). Prosody–Voice Screening Profile (PVSP). Tuscon, AZ: Communication Skill Builders). Overall, the children presented with noticeable problems with stress and resonance quality. There were some difficulties noted with rate, loudness, and laryngeal quality, but there were no consistent difficulties with phrasing or pitch. This suggested that prosody and voice characteristics in this population are different from those typically observed in children with severe to profound hearing impairments though some problem areas remain. Some developmental trends were also observed. These findings suggest that cochlear implants offer some significant benefits to children with hearing impairment in terms of prosody and voice outcomes. Learning outcomes: The reader will be able to: (1) identify aspects of prosody and voice that have been noted as problematic for individuals with severe to profound hearing impairment, and (2) list potential differences between the prosody and voice characteristics of children with cochlear implants and classic descriptions of the speech of individuals with hearing impairment.

Fitting back in: Adolescents returning to school after severe acquired brain injury

Purpose. To explore the experiences of Australian adolescents with severe acquired brain injury (ABI) and their families as the adolescent returned to school. In particular, to understand the influence of services and support on the school return.Method. In-depth interviews conducted over a two-year period with families who had an adolescent with a recent severe ABI (mean age 15 years, 11 months) analysed using a grounded theory approach.Results. Two critical phases for adolescents returning to school post ABI were identified: organizing the school return and being back at school.Experience in these phases was influenced by length of school absence, extent of noticeable and hidden problems and school response to the students' return post injury. The central concept characterizing experience was the challenge of fitting back in. Some adolescents fitted back in adequately and continued school participation. Those that did not fit in tried again by revisiting the organizing phase, re-evaluated their school experience and either continued or left school.Conclusions. Adolescents with ABI faced the challenge of fitting back in when they returned to school. This was either facilitated or hindered by the extent and quality of organization, communication and support from parents, schoolteachers and the rehabilitation team.

Long-term efficacy after switch from protease inhibitor-containing highly active antiretroviral therapy to abacavir, lamivudine, and zidovudine

Long-term efficacy after switch from protease inhibitor-containing highly active antiretroviral therapy to abacavir, lamivudine, and zidovudine

Impediments to implementing evidence-based mental health in developing countries

Mental and behavioural disorders are among the most important causes of morbidity and disability in both the developed and the developing world.1 As a proportion of total morbidity and disability,...

Observation of single-ion induced charge collection in diode by a heavy ion microbeam system

In order to study the phenomena of single event upset (SEU), investigations of properties of single event transient current (SETC) in micro-scale semiconductor devices are in progress at the JAERI Takasaki heavy ion microbeam single-ion hit system. Irradiation damage effects are noticeable problems in SETC measurement, especially when a device is irradiated continuously by high-energy heavy ions in an area of 1 μm level. On the other hand, confined irradiation damages in such narrow localized area can be a useful landmark to indicate how large area or region of the device to be concerned with charge collection events. This information is very important for designing micro-scale devices with high SEU tolerance. When a micro-scale test device of silicon carbide (SiC) pn diode was irradiated by single 12 MeV nickel ions with a beam spot size of 1 μm in FWHM, successive irradiation damage effects were observed in the form of attenuation of the current pulse heights and the amount of total charge collected. The lateral extent of charge collection induced by every ion injection was evaluated by analyzing these data. The extent of charge collection in depth direction will be also discussed in conjunction with the thickness of the sensitive layer and the range of the projectiles.

The baltic environmental information dissemination system: using environmental informatics as a tool for sustainable development in the Baltic Sea region

The on-going economic development of EU-countries as well of the countries in the C&E European region has been leading to a significant use of a great deal of natural resources as well as to noticeable environmental problems. The lack of a wide-spread environmental awareness from the side of those acting in various sectors (industry, public administration, users) sometimes inhibit the implementation of legislation already available as well as the introduction of new technologies deriving, from example, from marine research. An example of this state of affairs is seen in respect of the implementation of the recommendations deriving from Baltic 21 and VASAB 2010, which illustrate the advantages from a cross-sectorial, open mechanism for the dissemination of environmental information in the region. There are various organisations today which act as suppliers of environmental information in the Baltic Sea Region. However, few, if any, are providers concerned with the various ways in which information on matters related to sustainable development is being used by various groups and audiences. This state of affairs makes it necessary to enhance the current mechanisms and approaches in place, so as to enable the wide-range of environmental information available today from areas such as marine research, to be more widely used. It is equally important that the didactic or educational potential of such information be exploited, so as to not only inform, but also to educate various groups and the general public on matters concerned with the environment in European closed seas and give information to planners and politicians to prepare decisions. In order to address such needs, the project "Baltic Environmental Information Dissemination System (BEIDS)" was set in motion. BEIDS has been taking advantage of the most modern information technologies and has been acting as a focal point for the circulation of intelligent information on aspects of the marine environment, but also emphasising related areas such as transport and sustainable development issues, among a sample of six BSR countries: Denmark, Finland, Germany, Sweden (EU) and Lithuania and Poland (non-EU), contributing to networking and know-how exchange, complementing efforts towards transregional cooperation in sustainable spatial planning on the basis of Baltic 21. The results reached to date include: increased awareness of matters related to sustainable development in the six participant countries; enhanced communication exchange and networking among the sample nations; improved information flow and increased participation in events, activities and programmes across the Baltic Sea Region. BEIDS is a prime example of the feasibility of using environmental informatics as a tool for sustainable development.

The Baltic environmental information dissemination system: a tool for sustainable development in the Baltic Sea region

The on‐going economic development of EU‐countries as well of the countries in the Central and Eastern (C&E) European region has been leading to a significant use of a great deal of natural resources as well as to noticeable environmental problems. Focuses on the project “Baltic environmental information dissemination system (BEIDS)” which has been acting as a focal point for the circulation of intelligent information on aspects of the marine environment among a sample of seven Baltic countries: Denmark, Finland, Germany, Sweden (EU) and Lithuania, Poland and Russia (non‐EU), contributing to networking and know‐how exchange, complementing efforts towards transregional cooperation in sustainable spatial planning on the basis of Baltic 21. The results reached to date include: increased awareness of matters related to sustainable development in the six participant countries; enhanced communication exchange and networking among the sampled nations; improved information flow and increased participation in events, activities and programmes across the Baltic Sea region. BEIDS is a prime example of the feasibility of using marine research as a tool for sustainable development and the results reached over the first two years are reviewed in this paper.

In vivo experiment leading to clinical application of an electrohydraulic ventricular assist device with magnetic coupling.

We developed an electrohydraulic ventricular assist device with magnetic coupling. The integrated system consists of a blood pump, a water conduit for pressure transmission, a bellows type pumping sac, an actuator for transforming the circular motion of a motor to the linear motion of a pusher plate attached to the pumping sac with magnetic coupling, and a controller. The purpose of the coupling was to prevent excessive sucking against the atrial wall. Number 21 Medtronic Hall (Irvine, CA) mechanical valves were used in the inflow and outflow ports of the blood pump. Maximum dynamic stroke volume was 48 ml, and against a mean afterload of 100 mm Hg, maximum pump output was 7 L/min. Chronic in vivo experiments were performed in three sheep, and during these evaluations the system showed no noticeable problems related to mechanical or electronic devices. When left atrial pressure decreased below 0 mm Hg, the magnetic coupling system decoupled the pumping sac and pusher plate with satisfactory reliability. The device was clinically applied in a postoperative patient with chronic dilating cardiomyopathy, and no significant device related problems ensued. These results prove that the electrohydraulic ventricular assist system with magnetic coupling is a suitable ventricular assist device.

Effective Treatment of Minor Head Injury and Understanding Its Neurological Consequences

Minor head injury (MHI) is typically associated with coma and posttraumatic amnesia of short duration. Resulting impairment has been found in neurological and cognitive functioning, although these deficits tend to be brief in duration. A review of the literature reveals that although considerable research has been done on MHI, there remain a few critical issues that require resolution. First, one of the more noticeable problems relates to the fact that MHI does not have well-defined lower limits, which can lead to individuals being categorized as having an MHI despite never enduring trauma to the brain. The second problem relates to the failure of researchers to differentiate between cognitive deficits and postconcussion symptoms (PCS) when assessing outcome. Because PCS can occur in the absence of head injury and are often present beyond the period of cognitive recover from MHI, the two clearly result from different factors. Finally, many preinjury factors (age, personality) and postinjury factors (stress, neurological complications) interact with cognitive functioning and significantly affect recovery, which confounds the study of outcome. These problems are reviewed and discussed.

Performance analysis of the full-scale egg-shaped digester in treating sewage sludge of high concentration

A full-scale investigation was conducted to evaluate the performance of an egg-shaped digestion tank in treating sewage sludge of high concentration. The experiment was continued over a half year at 36°C, and the influent concentration of sewage sludge to the digester was controlled at about 50 g/L (5%) with a centrifugal thickener. The total solids (TS) in the raw sludge contained 20% inorganic matters and 80% volatile solids (VS), which were further composed of carbohydrates (45.4%), proteins (34.8%), lipids (13.1%) and volatile fatty acids (about 9.2%). At the mesophilic egg-shaped digestion tank with the retention time of 30 days, the removal efficiencies of carbohydrates, lipids, proteins and VFA reached 75%, 50.6%, 46% and 100%, respectively, and the reduction efficiencies of TS, VS, SS, VSS were 44.2%, 56.6%, 46.6% and 61.9%, respectively. The result of gas production showed that 1 m3 of influent concentrated sludge could produce 21 m3 of digestion gas containing 61% of methane. Of all influent sludge COD, about 57% was converted to methane and as a result, 1 kg of influent VS produced 0.531m3 digestion gas. There was no noticeable scum and foaming problems in the egg-shaped digesters, although they have been continuously operated for over ten years. The metabolic activities and populations of individual trophic groups of bacteria in the digester were also elucidated in this study.

Minor head injury: attempts at clarifying the confusion.

Traumatic brain injury (TBI) refers to a broad range of neurological, cognitive and emotional factors that result from the application of a mechanical force to the head. Mechanical force can be applied on a continuum from none to very severe, and the extent of brain injury is related to the severity of this force. A review of the literature reveals that, while considerable research has been done on minor head injury, there remain several major sources of confusion. First, one of the most noticeable problems relates to the fact that the mild head injury has lower limits which are vaguely defined. This leads to individuals being categorized as having sustained a mild TBI despite minimal or no neurological damage being present. A second source of confusion in the literature is related to the failure to differentiate between cognitive consequences of TBI and post-concussion symptoms (PCS). Since PCS can occur in the absence of head injury, and are often present beyond the period of cognitive recovery from mild TBI, the two clearly result from different factors. Researchers have often failed to separate these two factors when studying recovery of function, and this has led to varying findings on outcome. Finally, many pre-injury factors (age, education, emotional adjustment) and post-injury factors (pain, family support, stress) interact with cognitive functioning and significantly affect recovery from TBI. These problems are reviewed and discussed.

EFFICACY OF CROMOGLYCATE IN PERSISTENTLY WHEEZING INFANTS

Purpose of the Study. To evaluate the effectiveness of sodium cromoglycate in the treatment of persistent wheezing in children ages 4 to 12 months. Study Population. Thirty-one asthmatic infants without such complicating factors as gastroesophageal reflux, cystic fibrosis, bronchopulmonary dysplasia, etc, were enrollled. Sixteen received active medication and 15 received placebo. Methods. All 31 infants were observed for 3 weeks before the final enrollment with symptom scores recorded based on cough, wheeze, thoracic indrawing, and sleep pattern. Any noticeable problems were treated with albuterol delivered by a nebulizen and tightly fitting face mask. Pulmonary function parameters were determined by the "squeeze technique" on all enrollees. For the next 6 weeks, 16 infants received 40 mg of sodium cromoglycate in 4 mL solution via the nebulizer three times a day and 15 infants received 4 mL of normal saline three times a day. Symptom scores were meticulously recorded and again pulmonary function studies were performed. Findings. There were no significant differences noted between the sodium cnomoglycate group or the placebo group that led the investigators to conclude that sodium cromoglycate was not an effective agent in controlling asthma in very young infants. Reviewer's Comments. This appeared to be a very well done investigation and employed twice the dose of sodium cromoglycate e.g. 40 mgm tid, than most of us would use. It certainly makes one wonder especially in view of Dr. Shirley Murphy's similar results with sodium cromoglycate in premature newborns and its failure to prevent BPD. The use of inhaled corticosteroids to manage asthma in this young group of patients deserves such a carefully conducted study.

Image analysis techniques for petrographic analysis

A system has been developed which is capable of performing major maceral group analysis, using image analysis, based on morphological features as well as grey scale shading. The main advantage of the system lies in its ability to distinguish liptinite from resin. The potential problems with the system have, in practice, proved to be minor and have not noticeably affected the results obtained. However, more noticeable problems may be encountered with fine coal particles. The method has been modified to measure “reactive” fractions of coal and a method using fluorescence is being developed for liptinite determination.

Several Problems concerning the History of Besshi Copper Mine

The Besshi Copper Mine was opened in 1691 and was closed in 1972. Throughout the Tokugawa and the modern periods, the Besshi Copper Mine had kept the representative position among the copper mines in Japan. From beginning to end, the Besshi Copper Mine had been under the management of Sumitomo and its family companies. It is a well known fact that the Besshi Copper Mine was the resources which, directly or indirectly, enabled Sumitomo to establish and to develope various businesses in the modern period. In the present paper, several noticeable problems concerning the history of mining of the Besshi Copper Mine will be treated.

An alternative approach to elastodynamic crack problems in an orthotropic medium

A similarity transformation is used to reduce the system of second-order equations, governing elastodynamic plane problems in an orthotropic medium, to a first-order elliptic system of the Cauchy-Riemann type. A complex variable notation is then introduced to derive in a straightforward way the solution of two noticeable elastodynamic crack problems.

ChemInform Abstract: IRON OXIDE SEMICONDUCTOR ELECTRODES IN PHOTOASSISTED ELECTROLYSIS OF WATER

AbstractPolykristalline n‐leitende F e‐oxid‐,Elektroden, die durch Erhitzen von Fe‐Proben unterschiedlicher Herkunft ( ;z.B. Zonenschmelzeisen, magnetisches Eisen und kaltgewalzter Stahl) in Luft dargestellt werden, weisen eine unerwartet kleine Bandlücke auf.

Iron Oxide Semiconductor Electrodes in Photoassisted Electrolysis of Water

The preparation of polycrystalline n‐type iron oxide electrodes by heating of iron samples in air is reported. The behavior of these electrodes in aqueous solutions of different pH values in the presence and absence of illumination is shown. The photocurrent response of these electrodes to all wavelengths in the visible region is seen. Photoassisted electrolysis of water occurs at these wavelengths resulting in the evolution of oxygen bubbles at the iron oxide electrodes with no noticeable corrosion problems in pH 4.0 acetate buffer to solutions