bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive factors underlying the impact of postmigration stressors on subjective well‐being: Well‐being comparisons and self‐efficacy
Authors: Churbaji Dana , Morina Nexhmedin
Published: October 2023

Background

Migration and the resulting challenges in the host country can have a profound impact on the mental health of refugees and intensify preoccupation with one's own well‐being. Yet, cognitive factors underlying the adverse impact of postmigration stressors are poorly understood.

Objective

We aimed at exploring the frequency and nature of well‐being comparisons in the context of flight and migration using the Comparison Standards Scale for Well‐being (CSS‐W), which assesses well‐being related social, temporal, counterfactual, criteria‐based and dimensional aversive and appetitive comparisons. We further aimed at examining the mediating role of well‐being comparisons and general self‐efficacy in the relationship between postmigration stressors and psychological well‐being.

Methods

We conducted a survey with 1070 Arabic speaking forcibly displaced people in Germany assessing well‐being comparisons, general self‐efficacy, postmigration stressors, subjective well‐being and social media engagement.

Results

Factor analysis of the CSS‐W yielded a theoretically grounded two‐factor structure proposing an aversive (mostly upward) and an appetitive (mostly downward) comparison factor. Aversive and appetitive comparisons were reported by more than 99% of participants, with temporal comparisons being reported by 98.7% of participants. Postmigration stressors were significantly related to subjective well‐being and aversive well‐being comparisons and general self‐efficacy partially mediated this relationship. Appetitive well‐being comparisons, however, were not significantly related to neither postmigration stressors nor general self‐efficacy.

Conclusion

Aversive well‐being comparisons and general self‐efficacy seem to play a significant role in the adverse effects of postmigration stressors on subjective well‐being. Longitudinal research is needed to examine the directional dynamics between general self‐efficacy, well‐being comparisons and postmigration stressors.
Design and analysis of compact dual‐band WPT system using capacitively loaded interdigital capacitor
Authors: Atallah Hany A.
Published: October 2023

In this paper, a noteworthy compact dual‐band wireless power transfer (DB‐WPT) system is presented and studied. This DB‐WPT system is proposed using a capacitively loaded interdigital capacitor which reduces the size of the whole system, lessens the number of the attached surface mount elements, and accomplishes high efficiencies. An interdigital capacitor is printed in the ground plane of the design and loaded with a chip capacitor to produce dual bands. The operation of the system is verified by fabricating the proposed DB‐WPT system, which shows measured coupling efficiencies of 96% and 98.8% at 0.53 and 1.1 GHz, respectively at a transfer space of 12 mm. The fabricated structure has dimensions of 13.5 mm × 20 mm. The results show good agreement between the circuit model and the measurements. The idea of this design makes it applicable for compact near‐field WPT applications.
Cytological findings of phosphaturic mesenchymal tumor: Report of a case with summary of prior published cases
Authors: Das Oindrila , Mohin Md , Dey Soumya , Kar Anish , Singhania Pankaj , Adhikari Souvik , Chowdhury Subhankar , Chatterjee Uttara
Published: October 2023

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing tumor‐induced osteomalacia (TIO) and is characterized by secretion of FGF23, renal phosphate wasting and hypophosphataemia. It can be completely cured by resection and therefore its diagnosis is of utmost importance. Although the histology is well described, there is sparse literature on cytology of PMT and only three cases have been described so far. A 45‐year‐old lady presented with a non‐tender mass in hard palate for 2 years from which fine‐needle aspiration was done. The smears were paucicellular and showed bland spindle cells embedded in osteoid‐like stromal matrix in a hemorrhagic background. Here we take the opportunity to describe the cytological findings of PMT along with its cytological differentials and a summary of prior published cases.
Childhood trauma and outcome trajectories in patients with longstanding eating disorders across 17 years
Authors: Eielsen Hanna Punsvik , Ulvenes Pål , Hoffart Asle , Rø Øyvind , Rosenvinge Jan H. , Vrabel KariAnne
Published: October 2023

Background

A large proportion of patients with eating disorders (ED) report experiences of childhood trauma. Latent trajectory analysis in ED samples reveals the complexities in course and outcome and can explore the long‐term impact of adverse experiences in childhood.

Method

A total of 84 patients with longstanding ED were included. ED symptoms were assessed by the Eating Disorder Examination interview at discharge from inpatient treatment, and at 1‐, 2‐, 5‐, and 17‐year follow‐up, respectively. Change over time was examined using growth mixture modeling, allowing the number of trajectories to emerge through the data. Prevalence of childhood trauma was assessed, and its relation to class membership was tested.

Results

We identified four distinct classes: patients with (a) a continuous improvement in the entire follow‐up period, and scores within normal range at the end, “continuous improvement” (54.8%); (b) a high symptom level at baseline and moderate decrease over time, “high and declining” (22.6%); (c) initial ED scores below clinical cut‐off and stable symptoms throughout the course, “consistently low” (14.3%); and (d) with high scores initially, and a significant increase in symptoms over time, “high and increasing” (8.3%). A history of childhood sexual abuse (CSA) was overrepresented in classes with persistently high symptom levels and poor long‐term outcome

Discussion

Patients with longstanding ED displayed considerable diversity in trajectories of symptom change across 17 years. To improve long‐term outcome, enhanced treatment of sequelae from CSA seems essential.

Public Significance

Patients with longstanding eating disorders displayed four different trajectories of change in a 17‐year follow‐up study. Although there were significant changes over time, the majority of patients remained within similar symptom levels as they presented with at discharge from inpatient treatment. Exposure to childhood maltreatment was common within the sample. Childhood sexual abuse predicted poor long‐term outcome, which highlights the importance of trauma informed care.
Trimethyl Ammonium‐Assisted Interfacial Modification for Efficient and Stable Wide‐Bandgap Perovskite Solar Cells
Authors: Yi Fangxuan , Guo Qiyao , He Wei , Tang Qunwei , Duan Jialong
Published: October 2023

Wide‐bandgap (WBG) perovskite solar cells (PSCs) are acknowledged as promising candidates for tandem solar cells and building photovoltaics. It is well known that cesium‐based all‐inorganic halide WBG perovskites possess the comparable optoelectronic properties as the organic–inorganic counterparts, but exhibit superior thermal stability. Among them, CsPbIBr2 is considered a feasible material for tandem solar cells after balancing the bandgap and stability of the inorganic perovskite. However, CsPbIBr2 PSCs are often subjected to drastic interfacial charge recombination especially in carbon‐based device structure derived from the chemical bonding defects (i.e., uncoordinated Pb2+) naked on CsPbIBr2 soft lattice, which dramatically limits overall efficiency of CsPbIBr2 WBG PSCs. Herein, a trimethyl ammonium salt hexyltrimethylammonium bromide is presented for CsPbIBr2/carbon interfacial modification. Benefiting from the −N+(CH3)3 passivation effect and −C6H13 hydrophobic alkyl chain, the optimal device with highly smooth morphology and sufficient charge extraction exhibits a champion power conversion efficiency of 11.24% and improved long‐term stability with 99.7% and 79.7% efficiency retention under dry air atmosphere and continuous 85 °C thermal stress, indicating the valuable potential application of the lattice solidified CsPbIBr2 WBG PSCs.
Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug‐resistant epilepsy
Authors: Lähde Niina , Basnyat Pabitra , Raitanen Jani , Lehtimäki Kai , Rosti‐Otajärvi Eija , Peltola Jukka
Published: October 2023

Objective

To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug‐resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow‐up duration of up to 5 years.

Methods

The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID‐19 pandemic disrupted follow‐up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed‐effects (LMEs) model to compensate for the variation in follow‐up duration when predicting EpiTrack total score changes over 5 years.

Results

The median follow‐up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01–0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5‐fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1–2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3–4 ASMs.

Significance

Based on EpiTrack total scores, the LME model predicted a four‐point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs.

Plain Language Summary

Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug‐resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.
Closed‐form solution for natural frequency of flexible combined pile‐raft foundation
Authors: Bhaduri Aniruddha , Choudhury Deepankar
Published: October 2023

Dynamic attributes of flexible combined pile‐raft foundation (CPRF) hold paramount importance in assessing the behavior of it, especially in an earthquake prone area. The present study proposes a closed‐form solution for obtaining the natural frequency of flexible CPRF, where the piles and raft are represented as beam and thin plate respectively, lying on a two‐parameter Pasternak medium. Two simultaneous governing differential equations for the components are formulated and closed form solutions are obtained for finding the natural frequency and transient horizontal displacement of the foundation system. The complex soil‐structure interactions associated with the load‐bearing mechanism of CPRF is incorporated in the analysis scheme. The proposed method is validated with available centrifuge test result. Further parametric studies showcase that with decrease in raft thickness, the spectral acceleration response of the raft decreases. Also, for CPRF with high raft flexibility, the natural frequency of the foundation in dense sand is 34% and 53% higher compared to medium dense and loose sands, respectively. Thus, the present method can be reckoned as a notable contribution in comprehending the dynamic behavior of flexible CPRF.
Molecular imaging of tumour‐associated pathological biomarkers with smart nanoprobe: From “Seeing” to “Measuring”
Authors: Zhang Peisen , Li Wenyue , Liu Chuang , Qin Feng , Lu Yijie , Qin Meng , Hou Yi
Published: October 2023

Although the extraordinary progress has been made in molecular biology, the prevention of cancer remains arduous. Most solid tumours exhibit both spatial and temporal heterogeneity, which is difficult to be mimicked in vitro. Additionally, the complex biochemical and immune features of tumour microenvironment significantly affect the tumour development. Molecular imaging aims at the exploitation of tumour‐associated molecules as specific targets of customized molecular probe, thereby generating image contrast of tumour markers, and offering opportunities to non‐invasively evaluate the pathological characteristics of tumours in vivo. Particularly, there are no “standard markers” as control in clinical imaging diagnosis of individuals, so the tumour pathological characteristics‐responsive nanoprobe‐based quantitative molecular imaging, which is able to visualize and determine the accurate content values of heterogeneous distribution of pathological molecules in solid tumours, can provide criteria for cancer diagnosis. In this context, a variety of “smart” quantitative molecular imaging nanoprobes have been designed, in order to provide feasible approaches to quantitatively visualize the tumour‐associated pathological molecules in vivo. This review summarizes the recent achievements in the designs of these nanoprobes, and highlights the state‐of‐the‐art technologies in quantitative imaging of tumour‐associated pathological molecules.
Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high‐grade B‐cell lymphoma (HGBL) and diffuse large B‐cell lymphoma (DLBCL): Can we identify different prognostic subgroups?
Authors: Blomme Siska , De Paepe Pascale , Devos Helena , Emmerechts Jan , Snauwaert Sylvia , Cauwelier Barbara
Published: October 2023

High‐grade B‐cell lymphoma (HGBL)/diffuse large B‐cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC‐R and BCL2‐R and/or BCL6‐R—samples with MYC‐R and BCL2‐R (+/− BCL6‐R); n = 21, and HGBL/DLBCL with MYC‐R and BCL6‐R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called “alternative HGBL/DLBCL”—samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) “No alterations” (n = 55). Patients with HGBL/DLBCL‐MYC/BCL2 and “alternative” HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the “no alterations” group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC‐R and BCL6‐R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL‐MYC/BCL2. According to immunohistochemistry, “double/triple” expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups.
Optimization of calcium carbide residue utilization for producing high‐quality calcium carbonate
Authors: Yang Yuhang , Li Wenxiu , Xun Zhiwei , Yi Zhenwei , Wang Tao , Yu Zitao , Huang Yan , Gu Yongzheng
Published: October 2023

In light of the current situation where the utilization of calcium carbide slag yields low profits but holds significant potential for reducing carbon emissions, ammonium acetate was employed to leach calcium carbide slag. It also played a crucial role in regulating the products of indirect carbon dioxide carbonation when mixed with glycine and lye. Ammonium acetate's significance underscores its dual role in both the leaching and carbonation processes. This process yielded calcium carbonate with particle sizes smaller than 100 nm, with a purity of 98% and a single vaterite phase. The calcium carbide residue demonstrated an impressive CO2 uptake rate of 23.5%. Ammonium acetate exhibited an efficiency of 79.2% as a leaching agent. The ammonium acetate method demonstrated enhanced environmental friendliness and facilitated a more efficient carbon uptake rate of 23.5% compared to conventional indirect methods. Furthermore, the addition of lye, glycine, and ammonium acetate effectively extended the nucleation time of the calcium carbonate crystals and induced the formation of more vaterite intermediates with smaller particle sizes. The influence mechanism of compound additives on the carbonation reaction was revealed through kinetic analysis and molecular dynamics. This innovative approach offers a promising avenue for simultaneously treating solid waste and reducing CO2 emission. © 2023 Society of Chemical Industry and John Wiley & Sons, Ltd.
Prediction of Reaction Performance by Machine Learning Using Streamlined Features: NMR Chemical Shifts as Familiar Descriptors
Authors: Song Su‐min , Eun Kim Ha , Woo Kim Hyun , Chung Won‐jin
Published: October 2023

Machine learning (ML) has quickly emerged in synthetic organic chemistry to predict reaction outcomes such as yields and stereoselectivities. Notably, recent applications of the ML approach showed powerful performance in solving various chemical problems. However, the requirement of numerous descriptors and large datasets hampers the general use by non‐specialists. In this study, simple ML models were developed by utilizing easily available 13C‐NMR chemical shifts of the substrates as familiar descriptors to predict the site‐selectivity of geminal chlorofluorination of unsymmetrical 1,2‐dicarbonyl compounds. We identified that the feed‐forward neural network (FNN) model provides higher accuracy compared to other algorithms. Then, better prediction performance was acquired through streamlined models using minimal, only empirically relevant descriptors.
The evolving impact of engaging in leisure activities towards life quality: A longitudinal study of elderly in the UK
Authors: Aroean Lukman , Golgeci Ismail , Usrey Bryan
Published: October 2023

We examine the evolving impact of leisure activities (LA) on three key measures of the elderly's life quality: cognitive functioning (CF), psychological well‐being (PWB), and life enjoyment (LE). Using four waves of the English Longitudinal Studies of Ageing between 2008 and 2014 with 7097 respondents, we investigate how the elderly's LA influence their CF, PWB, and LE. Building on the theoretical perspective of being active in promoting psycho‐mental health, we confirm the positive impact of engaging in LA, such as going to the cinema/theatre and eating out, on the elderly's life quality. We further reveal the evolving impact of LA on the elderly's life quality. In a steady manner, LA directly promote the elderly's LE. In a declining pattern, CF and PWB mediate the relationships between LA and LE. As such, the impact of LA in sustaining perceived LE occurs dominantly as a direct effect during the activity. The elderly's LE throughout their old age can originate from engaging in LA, which mainly work directly rather than indirectly through CF and PWB.
Distribution Patterns and Habitat Characterization of Elmidae and Hydraenidae (Insecta: Coleoptera) in the Weidlingbach Near Vienna, Austria
Authors: Dietrich F. , Waringer J. A.
Published: October 2023

A total of 870 adult and 831 larval Elmidae and Hydraenidae were caught from September 1995 to September 1996 at the Weidlingbach, a fourth order tributary of the Danube near Vienna, Austria, using a Heß sampler at 14 sampling stations from source to mouth. Elmis maugetii (Latreille) and Riolus subviolaceus (Müller) accounted for 66.3% of the total, whereas Hydraena gracilis (Germar) was the most abundant Hydraenidae species.

Based on head width, instars 1–6 were collected in E. maugetii, instars 2–6 in R. subviolaceus and instars 3–6 in Limnius volckmari (Panzer) and Riolus cupreus (Müller); from the remaining species, only instars 4–6 were sampled.

E. maugetii was most abundant on coarse, moss‐covered substrates (median = 22.2 mm) exposed to high water velocity (median = 69.4 cm/s; range = 6.0–117.6 cm/s); the latter was also true for R. subviolaceus although it favoured smaller sediment grain sizes (median = 10.7 mm). Sites exposed to only moderate flow and with abundant filiform algae were preferred by Esolus parallelepipedus (Müller) and L. volckmari, whereas the Hydraenidae species, Esolus angustatus (Müller), R. cupreus and Oulimnius tuberculatus (Müller) were collected mostly at sites with moderate current speed and abundant moss‐covered pebbles of various size.

Species richness and population density increased from source to mouth. At the spring sampling site Elmidae and Hydraenidae were completely lacking.
An Incubator for the Simulation of a Fluctuating Light Climate in Studies of Planktonic Primary Productivity
Authors: Gervais Frank , Hintze Thomas , Behrendt Horst
Published: October 2023

A laboratory system for the quantification of phytoplankton photosynthesis under fluctuating light climate conditions is described. It consists of 2 temperature‐controlled incubators with a variable light supply, an algal batch culture in incubation bottles with appropriate stirrers and a set of oxygen electrodes to monitor algal photosynthesis. By the rotation of special grey filters between the incubator and the light source, a regular up and down movement in the water column is simulated in up to 7 parallel bottles. Different ratios of euphotic depth to mixing depth and different velocities can be applied. Simultaneously, 8 bottles can be incubated under constant light. The system is demonstrated in experiments with Chlamydomonas sp. Further possibilities of application are proposed.
Laboratory Studies of Parasite Transmission Aspects between Hydrobia spp. (Gastropoda) and Corophium volutator (Amphipoda)
Authors: Meissner Karin , Bick Andreas
Published: October 2023

Aspects of parasite transmission between Hydrobia spp. and Corophium volutator, first and second intermediate host of digenetic trematodes, were investigated under laboratory conditions. H. ventrosa is used as an intermediate host by several trematode species. Under laboratory conditions the most frequently observed emergence from H. ventrosa was of cercariae of Maritrema subdolum. The number of cercariae shed per day varied considerably. It was observed that 30 cercariae on average and up to 450 cercariae at maximum can emerge from a single H. ventrosa per day. Cercarial production continued until the death of the snails. The life‐span of cercariae of the species M. subdolum decreased as the water temperature increased. It can be concluded that under natural conditions the cercariae, after emerging, have a maximum period of 1 day in which to seek out their second intermediate host C. volutator. Almost all specimens of C. volutator exposed to cercariae of the species M. subdolum died within the test period of 6 days. High average cercarial densities caused short life‐spans (<50 h), while at lower densities longer survival times were possible. For cercariae of other Trematoda species, we were unable to find any equally clear evidence of a reduction in the survival rate of C. volutator within the test period. Mortality of C volutator, and other effects of infestation, as observed in our experiment, can be assumed to be a result of the penetration process of the cercariae but they also can be attributed to the mesocercariae.
Spatial Distribution, Food and Activity of Gomphus pulchellus SELYS 1840 (Insecta; Odonata; Gomphidae) from a Still Water Habitat
Authors: Alzmann Norbert , Köhler Bernd , Maier Gerhard
Published: October 2023

Distribution patterns of Gomphus pulchellus larvae in different sediments with different density of prey organisms were studied in the field in a small gravel pit lake in the south of Germany. Larval burrowing behaviour at different temperatures as well as food preference, consumption rates and activity were studied in laboratory experiments. In the study lake G. pulchellus larvae lived exclusively in places where macrophytes were present and in fine sediments (mean grain size <3 mm) with detritus cover. There was a significant positive correlation between larval density and density of food organisms suggesting that abundance of food is one of the determinants of larval distribution. In late autumn larvae migrated to deeper places probably to survive the winter. Low temperatures simulated in laboratory experiments did not induce larvae to burrow deeper. Larvae were always found in a sediment depth of 0.59–0.74 cm. Experiments with mixed prey showed that G. pulchellus larvae preferred tubificid worms and chironomid larvae over gammarids and ephemerid larvae. However, chironomid larvae which stayed in their tubes had a higher survival rate than those outside of tubes. Single‐prey experiments showed that G. pulchellus larvae can prey not only on benthic species but also on Daphnia from the open water. Functional‐response experiments showed that one G. pulchellus larva consumes a maximum of 2 to 3 tubificid worms or chironomid larvae per day, which corresponds to a maximum biomass (freshweight) of 5 to 30 mg per day. Video recordings of activity showed that G. pulchellus larvae cover long distances of up to 52 m per night on the substrate surface and that activity on the substrate surface started after midnight and ceased before sunrise. Consumption of Zooplankton prey and high activity above the substrate is interpreted as an adaptation of G. pulchellus larvae to the life in still water habitats.
Phytoplankton Community Structure in the Drainage Network of a Mediterranean River System (Aliakmon, Greece)
Authors: Montesanto Barbara , Tryfon Eleni
Published: October 2023

Phytoplankton structure was studied in Aliakmon river basin in April (highflow) and September (lowflow) 1995 in 29 sampling sites. Abundance and biomass were generally low and ranged considerably between sites. Benthic diatoms contributed greatly to the suspended algal assemblages whereas trends of potamoplankton development were observed downstream. Limnoplankton and especially chlorophytes developed in the areas where lentic conditions prevailed. The nature of changes in phytoplankton seemed to be both longitudinal and temporal. Multivariate techniques revealed that areas with distinctive morphology, hydrology and anthropogenic inputs tended to have similar phytoplankton composition although no simple relation with physico‐chemical factors can be shown. Human impact was more obvious on phytoplankton at the lowflow period. Generally, discharge played a significant role to the structure of phytoplankton communities.
Seasonal Development and Morphological Variability of Cyclotella ocellata (Bacillariophyceae) in the Eutrophic Lake Dagow (Germany)
Authors: Schlegel Ines , Scheffler Wolfram
Published: October 2023

The development of Cyclotella ocellata Pantocsek was studied systematically in the eutrophic, dimictic hardwater Lake Dagow from March to October, 1994. Cyclotella ocellata was the most important centric diatom in the lake with a maximum cell density of 6 × 106 cells 1−1. The seasonal development, characterized by a spring and a summer maximum, is considered in relation to environmental factors and the succession of the phytoplankton community. The amount of Cyclotella ocellata biomass as a proportion of the total phytoplankton biomass varied from 0.5 to 35%. In addition, seasonal changes in cell size and feature associated with sexual reproduction of Cyclotella ocellata were documented. Light and electron microscopic investigations demonstrate an extremely wide range of morphological variability of this natural population.
The Pharmacokinetics of TNP‐470, a New Angiogenesis Inhibitor
Authors: Figg William D. , Pluda James M. , Lush Richard M. , Saville M. Wayne , Wyvill Kathy , Reed Eddie , Yarchoan Robert
Published: October 2023

Study Objective. To characterize the pharmacokinetic profile of TNP‐470, a synthetic analog of fumagillin that is a potent inhibitor of angiogenesis and inhibits neovascularization in several solid tumor models.

Design. A dose‐escalation phase I clinical trial.

Setting. The National Institutes of Health.

Patients. Patients with human immunodeficiency virus‐associated Kaposi's sarcoma.

Interventions. The TNP‐470 dosage was increased in 13 sequential cohorts using a modified Fibonacci escalation scheme (4.6, 9.3, 15.4, 23.2, and 43.1 mg/m2). The drug was administered as a 1‐hour intravenous infusion. Serial blood samples were collected and assayed by reverse‐phase high‐performance liquid chromatography and the pharmacokinetics were characterized.

Measurements and Main Results. There was a linear relationship between the dose of TNP‐470 and both area under the curve to infinity (AUC[inf]) and time to maximum concentration (Cmax). The Cmax ranged between 6.6 ng/ml at the lowest dosage (4.6 mg/m2) and 597.1 ng/ml at the highest dosage (43.1 mg/m2). The agent was rapidly cleared from the circulation with a short terminal half‐life (0.88 ± 2.5 hr), which is consistent with preclinical data. Peak plasma concentrations of AGM‐1883, an active metabolite, ranged between 0.4 and 158.1 ng/ml.

Conclusion. Concentrations of TNP‐470 that have in vitro activity were achievable in vivo. The drug was rapidly cleared from the circulation after a single 1‐hour infusion. There was considerable interpatient variability in the clearance, but no evidence of saturable elimination. If more prolonged exposure is necessary for activity, administration of TNP‐470 by continuous infusion may be suitable.
Pharmacists' Ability to Influence Outcomes of Hypertension Therapy
Authors: Erickson Steven R. , Slaughter Richard , Halapy Henry
Published: October 2023

We measured the impact of pharmaceutical care on outcomes of antihypertensive therapy for patients with elevated baseline blood pressures who were attending an urban university‐affiliated internal medicine clinic. The intervention group received education about hypertension, drug and nondrug management, and assistance to enhance compliance. The pharmacist made recommendations to physicians regarding pharmacotherapy. The control group received no such education, and interventions relating to pharmacotherapy were only physician initiated. Over an average follow‐up of 5 months, significant decreases in mean blood pressures were noted for the intervention group from baseline to final assessment (156.5/144.5 mm Hg systolic, p=0.001; 91.6/86.9 mm Hg diastolic, p=0.01), with insignificant changes in mean pressures in the control group (153.7/151.0 mm Hg systolic, p=0.48; 90.4/87.8 mm Hg diastolic, p=0.29). Comparing the groups, the change in diastolic pressures was insignificant (4.7 vs 2.6 mm Hg intervention vs control, p=0.49), but the change in systolic pressure was more impressive (12.0 vs 2.7 mm Hg, respectively, p=0.05). There was no significant difference in SF‐36 Health Survey scores between groups. A significant decrease (p=0.03) in the SF‐36 physical functioning domain was seen in the intervention group, but no other significant changes in health‐related quality of life scores. Pharmaceutical care contributed to improved blood pressure control in these patients.
Serum Sickness Associated with 6‐Mercaptopurine in a Patient with Crohn's Disease
Authors: Andersen Judith M. , Tiede James J.
Published: October 2023

A 43‐year‐old man with a 19‐year history of Crohn's disease experienced serum sickness with acute lobular panniculitis and vasculitis within 2 weeks of initiating 6‐mercaptopurine therapy. He had no history of extraintestinal manifestations of Crohn's disease or drug allergy. Symptoms included disabling joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse drug reaction has not been described in association with 6‐mercaptopurine.
Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma
Authors: Wenzel Sally E.
Published: October 2023

Asthma is increasingly recognized as a mediator‐driven inflammatory process in the lungs. The leukotrienes (LTs) and prostaglandins (PGs), two families of proinflammatory mediators arising via arachidonic acid metabolism, have been implicated in the inflammatory cascade that occurs in asthmatic airways. The PG pathway normally maintains a balance in the airways; both PGD2 and thromboxane A2 are bronchoconstrictors, whereas PGE2 and prostacyclin are bronchoprotective. The actions of the LTs, however, appear to be exclusively proinflammatory in nature. The dihydroxy‐LT, LTB4, may play an important role in attracting neutrophils and eosinophils into the airways, whereas the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) produce effects that are characteristic of asthma, such as potent bronchoconstriction, increased endothelial membrane permeability leading to airway edema, and enhanced secretion of thick, viscous mucus. Given the significant role of the inflammatory process in asthma, newer pharmacologic agents, such as the sulfidopeptide‐LT antagonists, zafirlukast, montelukast, and pranlukast and the 5‐lipoxygenase (5‐LO) inhibitor, zileuton, have been developed with the goal of targeting specific elements of the inflammatory cascade. These drugs appear to represent improvements to the existing therapeutic armamentarium. In addition, the results of clinical trials with these agents have helped to expand our understanding of the pathogenesis of asthma.
Asthma Pharmacotherapy: Current Practices and Outlook
Authors: Kelly H. William
Published: October 2023

Owing to its high incidence and rapidly increasing prevalence in the United States population, and to the billions of dollars in associated costs, asthma is a significant public health problem. A variety of pharmacologic agents exist to manage asthma, but their efficacies vary, as do their costs. Recently published guidelines on asthma management set forth a four‐step approach that is guided by severity of disease and symptom control. These guidelines also suggest increased use of antiinflammatory agents, primarily inhaled corticosteroids, which carry a higher cost. Shifts in prescribing patterns among physicians who treat patients with asthma indicate that the guidelines are being adopted to some extent. However, some reluctance toward widespread use of corticosteroids remains, due to potential adverse effects as well as cost considerations. Alternatives to increased or high‐dose corticosteroid use include combination therapy with long‐acting bronchodilators. Newer medications that have more specific mechanisms of action, such as leukotriene synthesis inhibitors and leukotriene receptor antagonists, may offer another option.
Pharmacokinetics and Pharmacodynamics of Intravenous Agents for Ventricular Arrhythmias
Authors: Nolan Paul E.
Published: October 2023

Although no antiarrhythmic agent has ideal pharmacokinetic and pharmacodynamic characteristics, it is useful to evaluate antiarrhythmic agents in terms this ideal profile. The most desirable characteristics of an intravenous antiarrhythmic agent for treating ventricular arrhythmias are outlined. The basic pharmacokinetic and pharmacodynamic properties of the most commonly used agents for this indication—including amiodarone, bretylium, lidocaine, procainamide, and quinidine—are also reviewed, in light of this profile.
Pharmacokinetics of the Taxanes
Authors: Kearns Christine M.
Published: October 2023

The pharmacokinetics of the taxanes paclitaxel and docetaxel have been studied extensively in humans. Paclitaxel has distinctly nonlinear pharmacokinetics, with saturable distribution and elimination features. Docetaxel pharmacokinetics are well described by linear processes, although some investigators detected subtle nonlinear characteristics. Clinically, nonlinear pharmacokinetics produce a disproportional relationship between dose and drug exposure. This affects dose adjustments and calculation and use of dose intensity to compare chemotherapy regimens. Although the underlying mechanism of nonlinearity in paclitaxel disposition is not well understood, both metabolic and distributive processes may be involved.
Comparative Clinical Pharmacology of Cisplatin and Carboplatin
Authors: Murry Daryl J.
Published: October 2023

The platinum compounds cisplatin and carboplatin are active against a wide range of adult and pediatric malignancies. Whereas both exert their cytotoxic effect by incorporating into DNA, they have substantially different systemic and cellular pharmacology. In addition, their toxicity profiles are much different. Substantial interpatient pharmacokinetic variability and narrow therapeutic indexes of the two agents led to the development of several dosing strategies. Although these strategies reduce pharmacokinetic variability, their effect on improving patient outcome remains to be determined.
Effects of ACE Inhibitor Therapy on Quality of Life in Patients with Heart Failure
Authors: Wolfel Eugene E.
Published: October 2023

In addition to effects on survival, hemodynamics, and exercise capacity, quality of life has become an important outcome of therapy for chronic heart failure. A large clinical trial of the angiotensin‐converting enzyme (ACE) inhibitor enalapril reports that certain domains of health‐related quality of life (HRQL) have a long‐term impact on survival in patients with reduced left ventricular systolic function, regardless of symptoms of heart failure at diagnosis. Results of large‐scale clinical trials that measured the impact of several different ACE inhibitors on quality of life in these patients suggest benefits of the drugs, but data are confounded by a definite placebo effect. Studies are further confounded by high noncompletion rates for sicker patients, particularly beyond 1 year. Because measurement tools varied and different quality of life domains were evaluated, direct comparison of studies is problematic. Typically, HRQL measurements in patients receiving ACE inhibitors showed small improvement or did not differ significantly from those in placebo‐treated patients with long‐term follow‐up, although short‐term trials (< 6 mo) showed some benefit. Moreover, multicenter trials such as SOLVD, V‐HeFT II, and ramipril studies indicated that ACE inhibitors do not compromise and may actually improve certain components of quality of life in a large number of patients with chronic heart failure secondary to reduced left ventricular systolic function while having favorable effects on survival, exercise capacity, hemodynamics, or symptoms.
Cost‐Effectiveness of Enoxaparin versus Low‐Dose Heparin for Prophylaxis Against Venous Thrombosis after Major Trauma
Authors: Devlin John W. , Petitta Antonio , Shepard Alexander D. , Obeid Farouck N.
Published: October 2023

We attempted to determine health and economic outcomes from the perspective of an integrated health system of administering enoxaparin 30 mg twice/day versus heparin 5000 U twice/day for prophylaxis against venous thrombosis after major trauma. A decision‐analytic model was developed from best literature evidence, institutional data, and expert opinion. We assumed that 40% of proximal deep vein thromboses (DVTs) and 5% of distal DVTs are diagnosed and confirmed with initial or repeat duplex scanning; 50% of undiagnosed proximal DVTs result in pulmonary embolism; 2% and 1% of undiagnosed proximal DVTs will lead to readmission for DVT and pulmonary embolism, respectively, and pulmonary embolism‐related mortality rates range from 8–30%. Length of hospital stay data and 1996 institutional drug use and acquisition cost data were used to estimate the cost of enoxaparin and heparin therapy. Diagnosis and treatment costs for DVT and pulmonary embolism were derived from institutional charge data using costxharge ratios. A second analysis of patients with lower extremity fractures was completed. One‐way and multiway sensitivity analyses were performed. For 1000 mixed trauma patients receiving enoxaparin versus heparin, our model showed that 62.2 (95% CI −113 to −12) DVTs or pulmonary emboli would be avoided, resulting in 67.6 (8 to 130) life‐years saved at a net cost increase of $104,764 (−$329,300 to $159,600). Enoxaparin versus heparin resulted in a cost of $1684 (−$3600 to $9800) for each DVT or pulmonary embolus avoided and a discounted cost/life‐year saved of $2303 (−$8100 to $19,000). For 1000 patients with lower extremity fractures, enoxaparin versus heparin resulted in a cost of $751 (−$4200 to $3300) for each DVT or pulmonary embolus avoided and a discounted cost/life‐year saved of $1017 (−$10,200 to $6300). Although enoxaparin increases overall health care costs, it is associated with a cost/additional life‐year saved of only $2300, which is generally lower than the commonly used hurdle rate of $30,000/life‐year saved. The cost‐effectiveness ratio is more favorable in patients with lower extremity fractures than in the general mixed trauma population.
Administration of Filgrastim in Two Patients with Drug‐Induced Agranulocytosis
Authors: Castanheira Damary , Marzella Maria , Skirvin J. Andrew
Published: October 2023

Two patients experienced agranulocytosis associated with either procainamide or trimethoprim‐sulfamethoxazole. Both were treated with filgrastim in an attempt to decrease the duration of agranulocytosis. The first patient received 12 days and the second patient 4 days of filgrastim before white blood cell counts recovered. Published reports both support and refute the efficacy of filgrastim in this setting. The agent may be beneficial in certain cases of this disorder, but further investigation is necessary to determine if it has a definitive role.
Enhanced Metabolism of Levonorgestrel During Phenobarbital Treatment and Resultant Pregnancy
Authors: Shane‐McWhorter Laura , Cerveny Joli D. , MacFarlane Lori L. , Osborn Carol
Published: October 2023

Levonorgestrel implants (Norplant) are an alternative to oral contraceptives and medroxyprogesterone acetate intramuscular injections. An interaction may exist between levonorgestrel and agents that induce the hepatic microsomal enzyme system. A 21‐year‐old woman with a history of a seizure disorder, treated with phenobarbital, who received levonorgestrel implants became pregnant. After a normal delivery, she took oral contraceptives concomitantly with phenobarbital. Although she was educated about the importance of a backup method of contraception, the woman again became pregnant and delivered twins. A recent national survey of neurologists and obstetricians was conducted evaluating prescriber knowledge of interactions between oral contraceptives and anticonvulsants. Only 4% of neurologists and zero percent of obstetricians knew all the interactions between the six most commonly prescribed anticonvulsants and oral contraceptives. This case supports the importance of continued patient and prescriber education regarding the possibility of drug‐drug interactions in women taking anticonvulsants and hormonal contraceptives.
Measurement of Outcomes in Adults Receiving Pharmaceutical Care in a Comprehensive Asthma Outpatient Clinic
Authors: Knoell Daren L. , Pierson Jerome E , Marsh Clay B. , Allen James N. , Pathak Dev S.
Published: October 2023

We hypothesized that a pharmacist‐provided comprehensive education program in conjunction with care provided by a pulmonologist would lead to improved economic, clinical, and humanistic outcomes in adults with asthma, compared with similar patients receiving care from a pulmonologist alone. The experimental group reported receiving more information about asthma self‐management (p=0.001), were more likely to monitor peak flow readings (p=0.004), and had increased satisfaction with care, and perceived higher quality of care. Both groups had less lost productivity, fewer emergency department visits, fewer hospitalizations, and fewer physician visits, as well as improvement in symptoms scores within 45 days. Both groups improved in all functional status domains except the mental component score of the SF‐12. Our results show a positive impact on outcomes in adults with asthma who received pharmaceutical care.
Current Management of Human Bites
Authors: Bunzli William F. , Wright David H. , Hoang AnhThu D. , Dahms Robert D. , Hass Wayne F. , Rotschafer John C.
Published: October 2023

Human bites should be considered dangerous injuries with potentially serious complications. Their characteristics vary from an uninfected abrasion to a serious infection such as cellulitis or osteomyelitis. An estimated 10% of the injuries become infected; suspected pathogens include oral and skin flora. Management consists of history and examination, wound care, surgical intervention if necessary, assessment of risk of disease transmission, and appropriate antibiotic prophylaxis or treatment. The best choice for oral or intravenous antibiotic therapy remains the combination of a β‐lactam antibiotic with a β‐lactamase inhibitor. Among the most serious human bites are clenched fist injuries, which often require surgical intervention and intravenous antibiotic therapy.
Antiepileptic Drug Withdrawal—A Good Idea?
Authors: Buna Donna K.
Published: October 2023

Patients who are seizure free for 2 years or more are candidates for antiepileptic drug (AED) withdrawal. A MEDLINE search of the English language literature from 1980–1996 was performed to identify articles dealing with AED withdrawal in both adults and children. Factors examined included advantages and disadvantages of withdrawal, risks of relapse, prognostic factors of outcome, and methods of withdrawal. Advantages include psychosocial benefits, cost savings (direct drug costs, indirect monitoring costs), and avoidance of adverse effects and toxicity. The benefits must be balanced against the risks and impact of seizure relapse, which are different for each individual patient. A review of the prognostic factors that influence the risk of relapse will aid clinicians in determining appropriate candidates for AED withdrawal.