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All-dielectric metasurfaces supporting photonic bound states in the continuum (BICs) are an exciting toolkit for achieving resonances with ultranarrow linewidths. However, the transition from theory to experimental realization can significantly reduce the optical performance of BIC-based nanophotonic systems, severely limiting their application potential. Here, we introduce a combined numerical/experimental methodology for predicting how unavoidable tolerances in nanofabrication such as random geometrical variations affect the performance of different BIC metasurface designs. We compare several established all-dielectric BIC unit cell geometries with broken in-plane inversion symmetry including tilted ellipses, asymmetric double rods, and split rings. Significantly, even for low fabrication-induced geometrical changes, both the BIC resonance amplitude and its quality factor (Q-factor) are significantly reduced. We find that the all-dielectric ellipses maintain the highest Q-factors throughout the geometrical variation range, whereas the rod and split ring geometries fall off more quickly. The same behavior is confirmed experimentally, where geometrical variation values are derived from automated processing of sets of scanning electron microscopy (SEM) images. Our methodology provides crucial insights into the performance degradation of BIC metasurfaces when moving from simulations to fabricated samples and will enable the development of robust, high-Q, and easy to manufacture nanophotonic platforms for applications ranging from biomolecular sensing to higher harmonic generation.

Background: The objective of this review is to evaluate the associations between short-term exposure to radiofrequency electromagnetic fields (RF-EMF) and cognitive performance in human experimental studies., Methods: Online databases (PubMed, Embase, Scopus, Web of Science and EMF-Portal) were searched for studies that evaluated effects of exposure to RF-EMF on seven domains of cognitive performance in human experimental studies. The assessment of study quality was based on the Risk of Bias (RoB) tool developed by the Office of Health Assessment and Translation (OHAT). Random effects meta-analyses of Hedges's g were conducted separately for accuracy- and speed-related performance measures of various cognitive domains, for which data from at least two studies were available. Finally, the certainty of evidence for each identified outcome was assessed according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE)., Results: 57,543 records were identified and 76 studies (80 reports) met the inclusion criteria. The included 76 studies with 3846 participants, consisting of humans of different age, sex and health status from 19 countries, were conducted between 1989 and 2021. Quantitative data from 50 studies (52 reports) with 2433 participants were included into the meta-analyses. These studies were performed in 15 countries between 2001 and 2021. The majority of the included studies used head exposure with GSM 900 uplink. None of the meta-analyses observed a statistically significant effect of RF-EMF exposure compared to sham on cognitive performance as measured by the confidence interval surrounding the Hedges's g or the significance of the z-statistic. For the domain Orientation and Attention, subclass Attention - Attentional Capacity RF-EMF exposure results in little to no difference in accuracy (Hedges's g 0.024, 95 % CI [-0.10; 0.15], I 2  = 28 %, 473 participants). For the domain Orientation and Attention, subclass Attention - Concentration / Focused Attention RF-EMF exposure results in little to no difference in speed (Hedges's g 0.005, 95 % CI [-0.17; 0.18], I 2  = 7 %, 132 participants) and probably results in little to no difference in accuracy; it does not reduce accuracy (Hedges's g 0.097, 95 % CI [-0.05; 0.24], I 2  = 0 %, 217 participants). For the domain Orientation and Attention, subclass Attention - Vigilance RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.118, 95 % CI [-0.04; 0.28], I 2  = 41 %, 247 participants) and results in little to no difference in accuracy (Hedges's g 0.042, 95 % CI, [-0.09; 0.18], I 2  = 0 %, 199 participants). For the domain Orientation and Attention, subclass Attention - Selective Attention RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.080, 95 % CI [-0.09; 0.25], I 2  = 63 %, 452 participants); it may result in little to no difference in accuracy, but it probably does not reduce accuracy (Hedges's g 0.178, 95 % CI [-0.02; 0.38], I 2  = 68 %, 480 participants). For the domain Orientation and Attention, subclass Attention - Divided Attention RF-EMF exposure results in little to no difference in speed (Hedges's g -0.010, 95 % CI [-0.14; 0.12], I 2  = 5 %, 307 participants) and may result in little to no difference in accuracy (Hedges's g -0.089, 95 % CI [-0.35; 0.18], I 2  = 53 %, 167 participants). For the domain Orientation and Attention, subclass Processing Speed - Simple Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g 0.069, 95 % CI [-0.02; +0.16], I 2  = 29 %, 820 participants). For the domain Orientation and Attention, subclass Processing Speed - 2-Choice Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g -0.023, 95 % CI [-0.13; 0.08], I 2  = 0 %, 401 participants), and may result in little to no difference in accuracy (Hedges's g -0.063, 95 % CI [-0.38; 0.25], I 2  = 63 %, 117 participants). For the domain Orientation and Attention, subclass Processing Speed - >2-Choice Reaction Time Task RF-EMF exposure results in little to no difference in speed (Hedges's g -0.054, 95 % CI [-0.14; 0.03], I 2  = 0 %, 544 participants) and probably results in little to no difference in accuracy (Hedges's g -0.129, 95 % CI [-0.30; 0.04], I 2  = 0 %, 131 participants). For the domain Orientation and Attention, subclass Processing Speed - Other Tasks RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.067, 95 % CI [-0.12; 0.26], I 2  = 38 %, 249 participants); it results in little to no difference in accuracy (Hedges's g 0.036, 95 % CI [-0.08; 0.15], I 2  = 0 %, 354 participants). For the domain Orientation and Attention, subclass Working Memory - n-back Task (0-3-back) we found Hedges's g ranging from -0.090, 95 % CI [-0.18; 0.01] to 0.060, 95 % CI [-0.06; 0.18], all I 2  = 0 %, 237 to 474 participants, and conclude that RF-EMF exposure results in little to no difference in both speed and accuracy. For the domain Orientation and Attention, subclass Working Memory - Mental Tracking RF-EMF exposure results in little to no difference in accuracy (Hedges's g -0.047, 95 % [CI -0.15; 0.05], I 2  = 0 %, 438 participants). For the domain Perception, subclass Visual and Auditory Perception RF-EMF exposure may result in little to no difference in speed (Hedges's g -0.015, 95 % CI [-0.23; 0.195], I 2  = 0 %, 84 participants) and probably results in little to no difference in accuracy (Hedges's g 0.035, 95 % CI [-0.13; 0.199], I 2  = 0 %, 137 participants). For the domain Memory, subclass Verbal and Visual Memory RF-EMF exposure probably results in little to no difference in speed and does not reduce speed (Hedges's g 0.042, 95 % CI [-0.15; 0.23], I 2  = 0 %, 102 participants); it may result in little to no difference in accuracy (Hedges's g -0.087, 95 % CI [-0.38; 0.20], I 2  = 85 %, 625 participants). For the domain Verbal Functions and Language Skills, subclass Verbal Expression, a meta-analysis was not possible because one of the two included studies did not provide numerical values. Results of both studies did not indicate statistically significant effects of RF-EMF exposure on both speed and accuracy. For the domain Construction and Motor Performance, subclass Motor Skills RF-EMF exposure may reduce speed, but the evidence is very uncertain (Hedges's g -0.919, 95 % CI [-3.09; 1.26], I 2  = 96 %, 42 participants); it probably results in little to no difference in accuracy and does not reduce accuracy (Hedges's g 0.228, 95 % CI [-0.01; 0.46], I 2  = 0 %, 109 participants). For the domain Concept Formation and Reasoning, subclass Reasoning RF-EMF exposure results in little to no difference in speed (Hedges's g 0.010, 95 % CI [-0.11; 0.13], I 2  = 0 %, 263 participants) and probably results in little to no difference in accuracy and does not reduce accuracy (Hedges's g 0.051, 95 % CI [-0.14; 0.25], I 2  = 0 %, 100 participants). For the domain Concept Formation and Reasoning, subclass Mathematical Procedures RF-EMF exposure results in little to no difference in speed (Hedges's g 0.033, 95 % CI [-0.12; 0.18], I 2  = 0 %, 168 participants) and may result in little to no difference in accuracy but probably does not reduce accuracy (Hedges's g 0.232, 95 % CI [-0.12; +0.59], I 2  = 86 %, 253 participants). For the domain Executive Functions there were no studies., Discussion: Overall, the results from all domains and subclasses across their speed- and accuracy-related outcome measures according to GRADE provide high to low certainty of evidence that short-term RF-EMF exposure does not reduce cognitive performance in human experimental studies. For 16 out of 35 subdomains some uncertainty remains, because of limitations in the study quality, inconsistency in the results or imprecision of the combined effect size estimate. Future research should focus on construction and motor performance, elderly, and consideration of both sexes., Other: This review was partially funded by the WHO radioprotection programme. The protocol for this review was registered in Prospero reg. no. CRD42021236168 and published in Environment International (Pophof et al. 2021)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. BP is member of the ICNIRP Scientific Expert Group (SEG) on environment, BfS observer in the working group SSK-A630 of the German Commission on Radiological Protection and was German delegate of European Cost Actions BM0704 and BM1309 “EMF-MED”. GS is member of the Committee “Non-Ionizing Radiation” (SSK-A6) and member of the working group SSK-A630 of the German Commission on Radiological Protection. GS is chair of the Austrian Standardization Sub-Committee TSK-EMV-EMF “Electromagnetic Fields”. HDHs research is entirely funded by public or not-for-profit foundations. She has served as advisor to a number of national and international public advisory groups concerning the potential health effects of exposure to non-ionizing radiation, including the World Health Organization, the German Commission on Radiological Protection (member of the committee “Non-Ionizing Radiation” (SSK-A6) and member of the working group 5G (SSK-A630)) and the Independent Expert Group of the Swedish Radiation Safety Authority. JK is member of the ICNIRP Scientific Expert Group (SEG) on ultrasound and BfS observer in the working group SSK-A630 of the German Commission on Radiological Protection., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The radical pair mechanism is by now the most prominent candidate for a biologically relevant quantum effect of magnetic fields. Recently, N. Ikeya and J. R. Woodward demonstrated a magnetic field effect for sub-extremely low frequency (ELF) fields in the mT range by investigating the autofluorescence spectrum of flavin adenine dinucleotide in living HeLa cells. We apply a simple rate equation model to show numerically and analytically that magnetic field effects can be expected to exist in the whole ELF range., (© 2024 The Author(s). Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.)

Abstract: This report summarizes effects of anthropogenic electric, magnetic, and electromagnetic fields in the frequency range from 0 to 100 MHz on flora and fauna, as presented at an international workshop held on 5-7 November in 2019 in Munich, Germany. Such fields may originate from overhead powerlines, earth or sea cables, and from wireless charging systems. Animals and plants react differentially to anthropogenic fields; the mechanisms underlying these responses are still researched actively. Radical pairs and magnetite are discussed mechanisms of magnetoreception in insects, birds, and mammals. Moreover, several insects as well as marine species possess specialized electroreceptors, and behavioral reactions to anthropogenic fields have been reported. Plants react to experimental modifications of their magnetic environment by growth changes. Strong adverse effects of anthropogenic fields have not been described, but knowledge gaps were identified; further studies, aiming at the identification of the interaction mechanisms and the ecological consequences, are recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Abstract: This report summarizes the effects of anthropogenic radiofrequency electromagnetic fields with frequencies above 100 MHz on flora and fauna presented at an international workshop held on 5-7 November 2019 in Munich, Germany. Anthropogenic radiofrequency electromagnetic fields at these frequencies are commonplace; e.g., originating from transmitters used for terrestrial radio and TV broadcasting, mobile communication, wireless internet networks, and radar technologies. The effects of these radiofrequency fields on flora, fauna, and ecosystems are not well studied. For high frequencies exceeding 100 MHz, the only scientifically established action mechanism in organisms is the conversion of electromagnetic into thermal energy. In accordance with that, no proven scientific evidence of adverse effects in animals or plants under realistic environmental conditions has yet been identified from exposure to low-level anthropogenic radiofrequency fields in this frequency range. Because appropriate field studies are scarce, further studies on plants and animals are recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Background: Oxidative stress is conjectured to be related to many diseases. Furthermore, it is hypothesized that radiofrequency fields may induce oxidative stress in various cell types and thereby compromise human and animal health. This systematic review (SR) aims to summarize and evaluate the literature related to this hypothesis., Objectives: The main objective of this SR is to evaluate the associations between the exposure to radiofrequency electromagnetic fields and oxidative stress in experimental models (in vivo and in vitro)., Methods: The SR framework has been developed following the guidelines established in the WHO Handbook for Guideline Development and the Handbook for Conducting a Literature-Based Health Assessment). We will include controlled in vivo and in vitro laboratory studies that assess the effects of an exposure to RF-EMF on valid markers for oxidative stress compared to no or sham exposure. The protocol is registered in PROSPERO. We will search the following databases: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will also be manually searched., Study Appraisal and Synthesis Method: Data will be extracted according to a pre-defined set of forms developed in the DistillerSR online software and synthesized in a meta-analysis when studies are judged sufficiently similar to be combined. If a meta-analysis is not possible, we will describe the effects of the exposure in a narrative way., Risk of Bias: The risk of bias will be assessed with the NTP/OHAT risk of bias rating tool for human and animal studies. We will use GRADE to assess the certainty of the conclusions (high, moderate, low, or inadequate) regarding the association between radiofrequency electromagnetic fields and oxidative stress., Funding: This work was funded by the World Health Organization (WHO)., Registration: The protocol was registered on the PROSPERO webpage on July 8, 2021., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization (WHO) is currently assessing the potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMFs) in the general and working population. Related to one such health effect, there is a concern that RF-EMFs may affect cognitive performance in humans. The systematic review (SR) aims to identify, summarize and synthesize the evidence base related to this question. Here, we present the protocol for the planned SR., Objectives: The main objective is to present a protocol for a SR which will evaluate the associations between short-term exposure to RF-EMFs and cognitive performance in human experimental studies., Data Sources: We will search the following databases: PubMed, Embase, Web of Science, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles will be manually searched., Study Eligibility and Criteria: We will include randomized human experimental studies that assess the effects of RF-EMFs on cognitive performance compared to no exposure or lower exposure. We will include peer-reviewed articles of any publication date in any language that report primary data., Data Extraction and Analysis: Data will be extracted according to a pre-defined set of forms developed and piloted by the review author team. To assess the risk of bias, we will apply the Rating Tool for Human and Animal Studies developed by NTP/OHAT, supplemented with additional questions relevant for cross-over studies. Where sufficiently similar studies are identified (e.g. the heterogeneity concerning population, exposure and outcome is low and the studies can be combined), we will conduct random-effects meta-analysis; otherwise, we will conduct a narrative synthesis., Assessment of Certainty of Evidence: The certainty of evidence for each identified outcome will be assessed according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Performing the review according to this protocol will allow the identification of possible effects of RF-EMFs on cognitive performance in humans. The protocol has been registered in PROSPERO, an open-source protocol registration system, to foster transparency., (Copyright © 2021. Published by Elsevier Ltd.)

The National Voluntary Consensus Guidelines for Adult Protective Services (APS) were released in 2016 by the Administration for Community Living. These Guidelines help standardize systems to ensure the protection of older adults and adults with disabilities against abuse, neglect, and financial exploitation. Since their release, the extent to which state APS programs are aware of and using the Guidelines is unknown. This study examined the dissemination and implementation of the Guidelines across APS programs in the US. Researchers used the Diffusion of Innovations Theory to develop a survey sent to APS directors in all states. Forty-two states responded, and results were used to select a subset of states in which to conduct in-depth interviews. Awareness of the Guidelines was widespread but varied. Reported use of the Guidelines indicates that states are working to incorporate them into their practices. Respondents identified the need for more research and training in evidence-based practices.

Although channelrhodopsin (ChR) is a widely applied light-activated ion channel, important properties such as light adaptation, photocurrent inactivation, and alteration of the ion selectivity during continuous illumination are not well understood from a molecular perspective. Herein, we address these open questions using single-turnover electrophysiology, time-resolved step-scan FTIR, and Raman spectroscopy of fully dark-adapted ChR2. This yields a unifying parallel photocycle model integrating now all so far controversial discussed data. In dark-adapted ChR2, the protonated retinal Schiff base chromophore (RSBH + ) adopts an all- trans ,C=N- anti conformation only. Upon light activation, a branching reaction into either a 13- cis ,C=N- anti or a 13- cis ,C=N- syn retinal conformation occurs. The anti -cycle features sequential H + and Na + conductance in a late M-like state and an N-like open-channel state. In contrast, the 13- cis ,C=N- syn isomer represents a second closed-channel state identical to the long-lived P 480 state, which has been previously assigned to a late intermediate in a single-photocycle model. Light excitation of P 480 induces a parallel syn -photocycle with an open-channel state of small conductance and high proton selectivity. E90 becomes deprotonated in P 480 and stays deprotonated in the C=N- syn cycle. Deprotonation of E90 and successive pore hydration are crucial for late proton conductance following light adaptation. Parallel anti - and syn -photocycles now explain inactivation and ion selectivity changes of ChR2 during continuous illumination, fostering the future rational design of optogenetic tools., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

In recent years, gating and transient ion-pathway formation in the light-gated channelrhodopsins (ChRs) have been intensively studied. Despite these efforts, a profound understanding of the mechanistic details is still lacking. To track structural changes concomitant with the formation and subsequent collapse of the ion-conducting pore, we site-specifically introduced the artificial polarity-sensing probe p-azido-l-phenylalanine (azF) into several ChRs by amber stop codon suppression. The frequently used optogenetic actuator ReaChR (red-activatable ChR) exhibited the best expression properties of the wild type and the azF mutants. By exploiting the unique infrared spectral absorption of azF [ν as (N 3 ) ∼ 2100 cm -1 ] and its sensitivity to polarity changes, we monitored hydration changes at various sites of the pore region and the inner gate by stationary and time-resolved infrared spectroscopy. Our data imply that channel closure coincides with a dehydration event occurring between the interface of the central and the inner gate. In contrast, the extracellular ion pathway seems to be hydrated in the open and closed states to similar extents. Mutagenesis of sites in the inner gate suggests that it acts as an intracellular entry funnel, whose architecture and composition modulate water influx and efflux within the channel pore. Our results highlight the potential of genetic code expansion technology combined with biophysical methods to investigate channel gating, particularly hydration dynamics at specific sites, with a so far unprecedented spatial resolution.

In 2015, the Administration for Community Living (ACL) established the first federal "home" for Adult Protective Services (APS). This leadership has included working collaboratively with state Adult Protective Service systems to ensure that older adults and adults with disabilities are afforded the same protections against abuse, neglect, and financial exploitation regardless of where in the country they live. As part of that leadership, ACL created draft Voluntary Consensus Guidelines for State APS Systems. ACL undertook a process of public and stakeholder engagement and analyzed the resulting comments to improve upon the initial draft of the draft to arrive at the final version. This article examines the comments, including the concerns raised by the commenters about specific areas of the Guidelines, areas identified for future research, and reflections and opinions on the role of the federal government in guiding the development of the field of adult protection.

Although the α-alkylation of ketones has already been established, the analogous reaction using aldehyde substrates has proven surprisingly elusive. Despite the structural similarities between the two classes of compounds, the sensitivity and unique reactivity of the aldehyde functionality has typically required activated substrates or specialized additives. Here, we show that the synergistic merger of three catalytic processes-photoredox, enamine and hydrogen-atom transfer (HAT) catalysis-enables an enantioselective α-aldehyde alkylation reaction that employs simple olefins as coupling partners. Chiral imidazolidinones or prolinols, in combination with a thiophenol, iridium photoredox catalyst and visible light, have been successfully used in a triple catalytic process that is temporally sequenced to deliver a new hydrogen and electron-borrowing mechanism. This multicatalytic process enables both intra- and intermolecular aldehyde α-methylene coupling with olefins to construct both cyclic and acyclic products, respectively. With respect to atom and step-economy ideals, this stereoselective process allows the production of high-value molecules from feedstock chemicals in one step while consuming only photons.

Channelrhodopsins (ChRs) are light-gated ion channels that are widely used in optogenetics. They allow precise control of neuronal activity with light, but a detailed understanding of how the channel is gated and the ions are conducted is still lacking. The recent determination of the X-ray structural model in the closed state marks an important milestone. Herein the open state structure is presented and the early formation of the ion conducting pore is elucidated in atomic detail using time-resolved FTIR spectroscopy. Photo-isomerization of the retinal-chromophore causes a downward movement of the highly conserved E90, which opens the pore. Molecular dynamic (MD) simulations show that water molecules invade through this opened pore, Helix 2 tilts and the channel fully opens within ms. Since E90 is a highly conserved residue, the proposed E90-Helix2-tilt (EHT) model might describe a general activation mechanism and provides a new avenue for further mechanistic studies and engineering., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: In March of 2012, the U.S. Food and Drug Administration approved Sientra's application for premarket approval for its Silimed brand silicone gel implants, based on data from the largest silicone gel breast implant study to date. This was the first approval for shaped silicone gel breast implants. This article presents the results of Sientra's study through 5 years., Methods: Sientra's study is an ongoing, 10-year, open-label, prospective, multicenter clinical study designed to assess the safety and effectiveness of Sientra's implants in patients undergoing augmentation and reconstruction. A total of 1788 subjects were implanted with 3506 implants, including 1116 primary augmentation, 363 revision-augmentation, 225 primary reconstruction, and 84 revision-reconstruction subjects. Physical evaluations and complications were recorded at each visit. Effectiveness was measured by postimplantation bra cup size and assessment of subject satisfaction and quality of life. Of the 1788 subjects, 571 underwent magnetic resonance imaging to assess silent rupture. Safety endpoints were analyzed using the Kaplan-Meier method., Results: Across all cohorts, the risk of rupture was 1.8 percent (95 percent CI, 1.2 to 2.6 percent), the risk of capsular contracture (Baker grade III/IV) was 9.0 percent (95 percent CI, 7.6 to 10.6 percent), and the risk of reoperation was 23.8 percent (95 percent CI, 21.8 to 26.0 percent). Over 99 percent of surgeons reported satisfaction with the postoperative results, and subject satisfaction remained high 5 years after implantation., Conclusion: The 5-year results of Sientra's study continue to provide a comprehensive safety and effectiveness profile of Sientra's portfolio of Silimed brand shaped and round implants., Clinical Question/level of Evidence: Therapeutic, IV.

The light-activated microbial ion channel channelrhodopsin-2 (ChR2) is a powerful tool to study cellular processes with high spatiotemporal resolution in the emerging field of optogenetics. To customize the channel properties for optogenetic experiments, a detailed understanding of its molecular reaction mechanism is essential. Here, Glu-90, a key residue involved in the gating and selectivity mechanism of the ion channel is characterized in detail. The deprotonation of Glu-90 during the photocycle is elucidated by time-resolved FTIR spectroscopy, which seems to be part of the opening mechanism of the conductive pore. Furthermore, Glu-90 is crucial to ion selectivity as also revealed by mutation of this residue combined with voltage clamp experiments. By dynamic homology modeling, we further hypothesized that the conductive pore is flanked by Glu-90 and located between helices A, B, C, and G.

Online grief communities represent relatively new forms of peer support. However, the degree to which they are helpful for individual grieving processes is unknown. To date, no research has evaluated the type or quality of support exchanged in online grief communities. To begin to address these questions, this study analyzed 564 messages from internet grief websites to: (1) classify the type of helping skills used, and (2) extract themes contained in the content of the messages. Messages selected for analysis were the first response to an original post, assuming they would be the first effort to provide support to a grieving individual. Results revealed a majority of responses contained self-disclosure. Themes in the messages suggested provision of more than "one-way" support; messages themes also included exchanging hope for the future by sharing one's own story, validating the grief experience, providing resources, and exchanging psychosocial support. Clinical implications and research recommendations are discussed.

In animal experiments the new imidazoline derivative N-(2-imidazolin-2-yl)-N-(4-indanyl)amine (indanazoline, E-VA-16, as monohydrochloride active substance of Farial) is characterized by a pronounced vasoconstrictive action after local or intravenous application. This is due to a direct action of the compound on alpha-adrenergic receptors. When applied systemically E-VA-16 being a peripherally acting alpha-sympathomimetic induces a rise in blood pressure and a reduction of heart rate and exerts antiphlogistic, spasmolytic, hyperglycemic and diuretic actions. When given by the intranasal route the substance influences blood pressure and heart rate only at concentrations considerably higher than those intended for use in therapy. After enteral administration the effective doses also markedly exceed the single therapeutic doses. There was no evidence of side-effects restricting the use of the drug as compared to other imidazoline derivatives. Studies on the isolated perfused rabbit ear, however, indicated a broader therapeutic range in local application.

The pharmacokinetics of the 5:1 combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (thrimethoprim) (CN 3123, Nevin, Supristol) corresponds to the well known data of the single substances. Investigations on blood level, concentration in plasma water and excretion via urine and bile were done on experimental animals and with therapeutic dosage (single and repeated administration) on men. There were no alterations of the kinetics of the single substances due to drug interaction during simultaneous administration, neither qualitatively nor quantitatively. The dosage schedule elaborated is as follows: dosage interval=12 h, ratio initial dose: maintenance dose=2:1. For adults this regimen with a maintenance dose of 400 mg sulfamoxole and 80 mg trimethoprim results in a steady state of the minimal concentrations immediately before the following dose. These minimal concentrations in plasma water exceed the minimal inhibitory concentrations determined in vitro for most pathogens by several times.

Investigations were conducted with the combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) in a dose ratio of 5:1, with respect to pharmacological activity and possible side effects. The effects obtained with the combination CN 3123 were compared with those of the single substances. In a dose range comparable to that as used in clinical treatment, there were no effects on cardiovascular or respiratory functions, on functions of autonomic and central nervous system, on contractility of smooth muscles and on data of clinical chemistry such as urine and electrolyte excretion, blood sugar, blood coagulation and liver function tests. Doses which are 5 to 10 times higher than the initial dose or 10 to 20 times higher than the maintenance dose used in man caused an increase of urine and sodium excretion without influencing potassium and chloride output. There were no signs of sedation as alteration of motility or EEG patterns, but in mice and rats there was an increase in both duration and depth of anaesthesia caused by barbiturates or ether. Only in a dose range 30 to 40 times higher than the initial dose for man there were some slight alterations with respect to cardiovascular system and liver function tests. In vitro, with high concentrations of CN 3123 there was a weak, unspecific spasmolytic effect on the isolated ureter and an increase in the refractory period of the guinea pig atrium. There were no hints that the side effects seen with separate administration of high or very high doses of sulfamoxole or trimethoprim were increased or poteniated by their simultaneous administration. Slight side effects in animals were only observed with doses exceeding the tenfold of the doses for therapeutic use in men. Therefore, the therapeutic range of CN 3123 seems to be more than adequate.

The chemotherapeutically effective 5:1 combination N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) was investigated to determine any evidence of toxicological potentiation or new toxic signs. It was found that CN 3123 had a very low acute toxicity when administered orally to mice, rats and dogs (oral LD50: mouse greater than 12 000 mg/kg; rat greater than 14 000 mg/kg; dog greater than 1000 mg/kg body weight). The combination was also tolerated by rats and dogs in repeated doses administered over a period of 4 or 26 weeks, that greatly exceeded the therapeutic dose. The only change observed occurred in the thyroid, which in all doses administered exhibited a dose-related increase in weight accompanied by histological changes indicating an activation of thyroid function and a hypersecretion of basophilic thyrotropic cells in the anterior lobe of the pituitary. Six weeks after discontinuation of treatment this condition showed a tendency to reversibility or had already returned to normal. In dogs there was a dose-related increase in iodine uptake by the thyroid and a decrease in serum thyroxine over a period of 6 months under the highest dosage of CN 3123 administered. Whereas the thyroid changes observed under the combination could be reproduced with sulfamoxole, no effect on thyroid weight was observed in rats and dogs in the subacute toxicity phase of a comparative investigation with trimethoprim. Moreover, trimethoprim did not increase the effect of sulfamoxole on the thyroid gland. The effect of sulfamoxole on the thyroid is discussed in detail with a review of the literature. It can be characterized as species-specific for sulfonamides in mice, rats, rabbits and dogs but not in monkeys or in man and appears to be caused by the inhibition of the organic binding of iodine in the thyroid, whereby the predisposing factors must vary considerably from species to species. The thyroid hypertrophy observed is due to the activation of the regulatory cycle via the anterior lobe of the pituitary. The following systemic changes occurred after 600 mg CN 3123/kg, a lethal-toxic dosage and the highest administered in the study: reduced body weight, decreased food consumption leading to cachexia, slightly increased SGPT and alkaline phosphatase, slight thrombocyte depression, enlargement and increased fatty degeneration of the liver, occurrence of necrotic areas in the liver, hemosiderin accumulation in Kupffer's cells, and an increase of reticular cells in the spleen. The acute toxicity of CN 3123 and all major functional and histological changes under repeated administration were due exclusively to sulfamoxole. The combination sulfamoxole/trimethoprim gives no indication of toxicological potentiation or new toxic signs.