Minimizing Variability of Cascade Impaction Measurements in Inhalers and Nebulizers

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD)

Obniżenie wydajności PS II w igłach sadzonek jodły pospolitej (Abies alba MILL.) rosnących pod okapem modrzewia europejskiego i świerka pospolitego

We studied the down-regulation of PS II in saplings of the shade tolerant tree Abies alba Mill. growing under light-permeable canopy of Larix decidua characterised by high canopy openness (ca 40%) and under dense canopy formed by Picea abies of low openness (ca 18%) in the Karkonosze National Park. The seasonal pattern of maximum (dark adapted) quantum yield of PS II (FV/Fm) during the 2001 season, as well as the diurnal course of quantum yield of PS II (ФPSII) in August 2002 were determined. In spring 2001, FV/Fm in fir needles was reduced in both stands but recovered during the summer to near optimal values. This early-season decline indicating a long term down-regulation of PS II was consistently stronger under Larix canopy. Diurnal variation of ФPSII in August 2002 closely and inversely tracked the incident light level, with the declines more pronounced under Larix, where light flecks were more frequent and intense. Recoveries of ФPSII were, however, immediate and thus no evidence of light-fleck induced photoinhibition was apparent. In response to comparable light intensity, however, down-regulation of PS II was higher under the canopy of Picea than under Larix (two- to three-fold difference in regression slopes), suggesting an acclimation to higher light in firs growing under the Larix canopy. Thus, two time scales of PS II down-regulation were evident: long-term, seasonal down-regulation related probably to temperature (interacting with light) and short-term diurnal down-regulation influenced mainly by light conditions.Odwracalny proces fotoinhibicji w okresie wegetacyjnym i w ciągu dnia został zbadany przy zastosowaniu pomiarów fluoresceucji chlorofilu a w igłach bieżących przyrostów sadzonek jodły pospolitej (Abies alba MILL.) rosnących cztery lata pod okapem modrzewia europejskiego o wysokiej ażurowości (ca 40%) i okapem świerka pospolitego o niskiej ażurowości (ca 18%) w Karkonoskim Parku Narodowym. Wiosną, maksymalna wydajność kwantowa PS II (FV/Fm) w zaadoptowanych do ciemności igłach jodłowych była obniżona w obu drzewostanach, ale w ciągu lata powróciła do optymalnej wartości (powyżej 0,83). To przejściowe, jednak stosunkowo długotrwałe obniżenie Fv/Fm w ciągu roku świadczy o wystąpieniu fotoinhibicji, która w kwietniu i w czerwcu była silniejsza pod okapem modrzewia. Młode jodły w drzewostanie modrzewiowym były lepiej zaaklimatyzowane do światła niż w drzewostanie świerkowym. Wartości ФPSII w sierpniu 2002 malały wraz ze wzrostem poziomu światła. Większe obniżenie ФPSII nastąpiło w drzewostanie modrzewiowym, gdzie plamy świetlne (światło mozaikowe) występowały częściej i intensywniej. Nie stwierdzono jednak fotoinhibicji spowodowanej działaniem światła mozaikowego, gdyż obniżenie ФPSII było krótkotrwałe. W ciągu dnia sadzonki pod okapem świerka wykazały wyższe średnie godzinne wartości ФPSII. Przy takim samym poziomie światła, obniżenie wydajności PS II określone na podstawie porównania współczynników kierunkowych prostych regresji między wartościami PPFD a względnymi wartościami obniżenia wydajności PS II było jednak dwu- trzykrotnie większe (w zależności od zachmurzenia) pod okapem świerka, co wskazuje na większą podatność sadzonek rosnących w silnym ocienieniu na fotoinhibicję w porównaniu do tych, które były przystosowane do wysokiego poziomu światła pod okapem modrzewiowym. W igłach młodych jodeł rosnących pod okapem dojrzałych drzew stwierdzono dwa rodzaje obniżenia maksymalnej i rzeczywistej wydajności kwantowej PS II ze względu na ich występowanie w czasie i najważniejszy czynnik indukcji: długotrwałe, fotoinhibicyjne obniżenie wydajności PS II w ciągu roku spowodowane przez niskie temperatury powietrza oraz krótkotrwałe obniżenie wydajności PS II w ciągu dnia regulowane głównie przez promieniowanie świetlne docierające do dna lasu przez okap drzewostanu

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: A systematic review and meta-analysis of individual participant data

Contains fulltext : 174490.pdf (publisher's version ) (Open Access)Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.10 p