Significant Financial Interest Research Articles

Effects of Stimulus Pattern on Inspiratory Muscle Activation during High Frequency Spinal Cord Stimulation in an Animal Model

Background: High Frequency Spinal Cord Stimulation (HF-SCS) is a unique method of inspiratory muscle activation and has the potential to restore breathing in ventilator dependent tetraplegic subjects. Objective: To evaluate the pattern of diaphragm (D), parasternal (PA) and external intercostal (EI) activation during rectangular vs ramp-shape HF-SCS, compared to spontaneous breathing. Methods: In 8 anesthetized dogs, a stimulating disc electrode was positioned on the ventral surface of the spinal cord at the T2 level. Stimulus train duration for ramp-shape and rectangular HF-SCS was set at 1.3s since this duration approximated that occurring during spontaneous breathing. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes approximated that occurring during SB. The ramp-shape pattern of stimulation was linearly increased from zero to the desired stimulus amplitude. Single motor unit (SMU) EMG activity of the PA, EI and D muscles was assessed during SB and HF-SCS (following spinalization at the C2 level) with rectangular and ramp-shape stimulation patterns, in separate trials. Time of onset (To), b) time to peak discharge frequency (TTP) and c) peak firing frequency (PFF) were measured under each condition. To and TTP were determined relative to the onset of inspiratory flow and expressed as a percentage of inspiratory time (Ti). The patterns of the inspiratory muscle activation during HF-SCS were compared to that obtained during spontaneous breathing. Results: During SB, D was recruited first followed by PA and EI; mean ± SE To was 19.6±1.4, 32.1±2.4 and 40.4±2.3%Ti, respectively. During rectangular HF-SCS, To was 3.0±0.4, 5.8±1.2 and 4.3±0.9%Ti for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, To was 23.1±3.7, 33.6±4.5 and 39.9±4.6%Ti for D, PA and EI respectively (NS for each compared to SB). During SB, TTP was 65.2±2.2, 71.0±2.0 and 74.0±2.0%Ti for D, PA and EI. During rectangular HF-SCS, TTP was 30.4±3.7, 25.4±3.3 and 35.2±2.8%Ti, for D, PA and EI (p<0.05 for each compared to SB). During ramp-shape HF-SCS, TTP was 60.5±2.9, 58.2±2.7 and 62.6±6.0%Ti for Dia, PA and EI (p<0.05 for PA and EI compared to SB). During SB, PFF of SMUs of the D, PA and EI were 10.3±0.5, 12.8±0.4 and 12.2±0.7Hz, respectively. However, during rectangular HF-SCS, PFF were 14.0±0.6, 14.7±0.7 and 14.5±0.5Hz for D, PA and EI, respectively (p<0.05 for each compared to SB). During ramp-shape HF-SCS, PFF were 12.3±0.8, 13.8±0.9 and 12.6±1.2 for D, PA and EI, respectively (NS for each compared to SB). Conclusion: Activation of the inspiratory motoneuron pools via HF-SCS is receptive to different patterns of electrical stimulation.Ramp-shape HF-SCS compared to rectangular HF-SCS results in a more physiologic pattern of inspiratory muscle activation. National Institutes of Health grant no. R01 NS105785. Conflict of interest: Dr. A. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems (nos. 5,678,535 and 5,911,218). Dr. A. DiMarco and Dr. K. Kowalski hold the U.S. patents for technology related to the content of this study, Respiratory Muscle Activation by Spinal Cord Stimulation (no. 8,352,036). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lignite fly ash utilization for acid mine drainage neutralization and clean-up

Two fly ashes (FAs) originating from Kardia and Megalopolis power plants are used for the first time to amend the acid mining drainage (AMD) from the abandoned Ermioni and the active Kassandra Greek mining sites. The fly ashes employed are of type C, with Kardia fly ash (KFA) being mostly calcareous and Megalopolis’ (MFA) mostly siliceous. Both FAs were tested for their pH-regulating and metal-ions-removal efficiency. Regarding the acidity reduction both FAs proved equally efficient; by regulating the FA to AMD solution ratio, final pH values between 6 and 12.5 were attained using KFA while weakly acidic (pH = 6) to neutral solutions were produced in the case of MFA. Except for chromium ions, both FAs, also, proved equally effective in (heavy-)metal-removal for loadings higher than 5 g/50 mL acid waters. KFA, particularly, cleaned up the acid mine drainage solution from all metals even at a 0.5 g/50 mL loading. For KFA, metal removal was attributed to precipitation while in the case of MFA retention was found to occur via adsorption and/or complexation as well. Both FAs and AMD are largely produced as side effects of the two major Greek economic activities, i.e., electricity production and mining; using FAs to assess the AMD environmental impact can contribute to circular economy and, therefore, is of significant financial interest for Greece.

Hydroxyl radical protein footprinting for analysis of higher order structure

Tabled 1aAdapted from Johnson et al. [11].Hydrogen deuterium exchangeGlycine ethyl esterDiethylpyrocarbonateN-Ethylmaleimide (NEM)Fast photochemical oxidation of proteinsLabeling timescaleSeconds to hoursSeconds to minutesMinutesMinutes to hoursMicrosecondsType of labelReversibleReversibleReversible for most residuesIrreversible for LysIrreversibleIrreversibleSensitivity/specificityBackbone amide groupsCarboxylic acidsNucleophilic residuesN terminus, His, Lys, Tyr, Ser, Thr, and CysCys19 out of 20 amino acids (excluding Gly)Chemicals/materialsCommonly used buffers under physiological conditionsQuench solutionspH 2.5 (strong or weak acid)0°CDenaturing (urea,guanidine HCl)Reducing agents (TCEP)Pepsin digestionEDC stock solutionprepared freshly in PBS bufferMES/NaOH (pH = 5.5),PBS (pH = 6, 6.5, 7, 7.5),HEPES (pH = 8, 8.5)DEPC in acetonitrile in a molar excess of 4 10 mM imidazole added to quench the reactionNEM solution10 mm HEPES5% DMSOVarious buffer solutions based on proteinH2O2free glutamine radical scavengerQuench solution: free methionine and catalase (in vitro)LimitationsReversibility of the label limits its use for complex samples that require longer separation timesCarboxylic acid-specific labeling limits the proteins that can be studiedFree cysteine scramblingCysteine-specific labeling limits the proteins that can be studiedResidue-reactivity differences, complex data analysis, and expense of excimer lasera Adapted from Johnson et al. [11]. Open table in a new tab Hydroxyl radicals can be generated using various methods, including Fenton chemistry, radiolysis of water, and photolysis of hydrogen peroxide. The labeling timescale is based on the radical generation method with some labeling proteins on the nano- or microsecond timescale, which is faster than all other footprinting methods. HRPF has been successful in studying HOS in varied applications, including epitope mapping, ion channel dynamics, and viral protein studies. HRPF has also been used to study intact cells and in vivo systems.ADVANTAGES:General labeling strategy that can modify 19 of the 20 amino acids.Labeling is compatible with several widely used buffer systems.The irreversible nature of the label provides flexibility for postlabeling sample handling.Can identify protein interaction sites and regions of conformational changes.Can analyze complex systems such as cell lysates, intact cells, and Caenorhabditis elegans.Advancements in dosimetry have increased the quantitative power of the method.There have been efforts to automate labeling leading to higher throughput.CHALLENGES:Data analysis is complex, time consuming, and there is not a universal data analysis platform.Generating hydroxyl radicals on a fast timescale requires special instrumentation.Lower resolution than other structural methods.Difficult to identify interacting proteins in complex systems.Declaration of interestsL.M.J. discloses a significant financial interest in GenNext Technologies, Inc., an early-stage company seeking to commercialize technologies for protein higher-order structure analysis. Hydroxyl radicals can be generated using various methods, including Fenton chemistry, radiolysis of water, and photolysis of hydrogen peroxide. The labeling timescale is based on the radical generation method with some labeling proteins on the nano- or microsecond timescale, which is faster than all other footprinting methods. HRPF has been successful in studying HOS in varied applications, including epitope mapping, ion channel dynamics, and viral protein studies. HRPF has also been used to study intact cells and in vivo systems. ADVANTAGES:General labeling strategy that can modify 19 of the 20 amino acids.Labeling is compatible with several widely used buffer systems.The irreversible nature of the label provides flexibility for postlabeling sample handling.Can identify protein interaction sites and regions of conformational changes.Can analyze complex systems such as cell lysates, intact cells, and Caenorhabditis elegans.Advancements in dosimetry have increased the quantitative power of the method.There have been efforts to automate labeling leading to higher throughput. General labeling strategy that can modify 19 of the 20 amino acids. Labeling is compatible with several widely used buffer systems. The irreversible nature of the label provides flexibility for postlabeling sample handling. Can identify protein interaction sites and regions of conformational changes. Can analyze complex systems such as cell lysates, intact cells, and Caenorhabditis elegans. Advancements in dosimetry have increased the quantitative power of the method. There have been efforts to automate labeling leading to higher throughput. CHALLENGES:Data analysis is complex, time consuming, and there is not a universal data analysis platform.Generating hydroxyl radicals on a fast timescale requires special instrumentation.Lower resolution than other structural methods.Difficult to identify interacting proteins in complex systems. Data analysis is complex, time consuming, and there is not a universal data analysis platform. Generating hydroxyl radicals on a fast timescale requires special instrumentation. Lower resolution than other structural methods. Difficult to identify interacting proteins in complex systems. Declaration of interestsL.M.J. discloses a significant financial interest in GenNext Technologies, Inc., an early-stage company seeking to commercialize technologies for protein higher-order structure analysis. L.M.J. discloses a significant financial interest in GenNext Technologies, Inc., an early-stage company seeking to commercialize technologies for protein higher-order structure analysis.

Assessing Family Functioning Before and After an Integrated Multidisciplinary Family Treatment for Adolescents With Restrictive Eating Disorders

IntroductionPrevious studies applying the Lausanne Trilogue Play (LTPc), a semi-structured method for observing family dynamics, highlighted dysfunctional interaction patterns in the families of individuals affected by restrictive eating disorders (REDs). Family-centered approaches are considered the first-line treatment for severe cases of REDs in adolescence.ObjectivesTo investigate family functioning in the families of adolescents with severe REDs assessed before and 6 months after a multidisciplinary family treatment program that combined psychodynamic psychotherapy, parental role intervention and triadic or family-centered intervention.MethodsSixty-seven families of adolescent patients diagnosed with REDs were assessed for eligibility between July 2017 and October 2020. Family functioning was assessed using the clinical version of LTPc. Nutritional counseling and neuropsychiatric monitoring were also provided.ResultsWe observed a significant change in the family functioning score for the LTPc phase 2, in which the father interacts with his daughter while the mother acts as a silent observer. This suggests that the fathers, when playing an active role, could improve dyadic family functioning. The treatment was not found to change triadic functioning: a 6-month treatment may not be long enough to modify interactions at the triadic level.ConclusionsA brief multidisciplinary treatment program may significantly improve family functioning in the families of patients diagnosed with severe REDs. Although appropriate clinical trials are needed to further test the efficacy of this treatment, our study reinforce the concept that treatment programs targeting the individual patient and both the parents should be a first-line approach in adolescents with severe REDs.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Perceived Stress among Iranians during COVID-19 Pandemic; Stressors and Coping Mechanisms: A Mixed-methods Approach

IntroductionThis study was a mixed-methods study. We distributed a web-based 1scale (PSS-10), to measure perceived stress scores, through social networks from March 12 to 23, 2020. Then, we interviewed 42 students, 31 homemakers, 27 healthcare providers, and 21 male participants to identify the sources of stress and coping mechanisms.ObjectivesWe examined the correlates of stress among a large sample of Iranian citizens, the second country hit hard by the pandemic, and still a hot spot.MethodsThis anonymous survey had 19 items falling into two sections: sociodemographic data and Cohen’s 10-item perceived stress scale (PSS-10).ResultsA statistically significant difference was observed between the levels of perceived stress in individuals with different health statuses with a higher median of total PSS-10 scores reported for hospitalized individuals. The total PSS-10 scores were higher in those who were practicing self-isolation, had a relative affected with COVID-19 disease, and had experienced the death of a relative due to COVID-19 disease.ConclusionsThis study highlighted the most vulnerable groups overloaded with stress in society and the sources of their stress. Furthermore, we identified the groups that perceived lower levels of stress along with their coping mechanisms. The most frequent source of stress among the most stressful groups including homemakers, students, and health care workers has directly related to their job and their principal role in this period. Abstract thought about the COVID-19 pandemic and its complications were more prevalent among students while homemakers and health care providers showed concrete thinking about the COVID-19 pandemic.DisclosureI have no significant financial interest, consultancy, or other relationship with products, the manufacturer(s) of products, or providers of services related to this abstract?

Electronic smart-hub based intervention during COVID-19 in a rural Psychiatry of Old Age service in North-West Ireland

IntroductionThe COVID-19 pandemic caused significant disruptions in services and necessitated innovation to continue care provision to the vulnerable population of older adults with psychiatric needs.ObjectivesThe objective of this study was to examine the experiences of staff and patients using a hands-free electronic smart-hub (eSMART hub) intervention to keep patients connected with psychiatry of old age following COVID-19 restrictions.MethodsA risk stratification register was created of all patients known to the Psychiatry of Old Age service in the North-West of Ireland to identify those at highest risk of relapse. These patients were offered a smart-hub with remote communication and personal assistant technology to be installed into their homes. Smart-hubs were also installed in the team base to facilitate direct device to device communication. Semi-structured qualitative interviews were conducted with 10 staff members and 15 patients at 6-12 months following the installation of the smart-hubs.ResultsThe smart-hubs were utilized by the POA team to offer remote interventions over video including clinician reviews, regular contact with key workers and day-hospital based therapeutic interventions such as anxiety management groups and OT led physical exercises. Patients also used the personal assistant aspect of the hub to attend to personal hobbies such as accessing music and radio. Positive feedback related to companionship during isolation and connectivity to services. Negative feedback was mainly related to technology, particularly internet access and narrow scope of communication abilities.ConclusionsElectronic smart-hub devices may offer an acceptable avenue for remote intervention and communication for isolated high-risk older persons.DisclosureThe smart hub devices used in this study were donated by Amazon. However, the company was not involved in any other aspect of the study and the researchers have no significant financial interest, consultancy or other relationship with products, manufactur

Prognostic Accuracy of DSM-5 Attenuated Psychotic Symptoms in Adolescents: Prospective Real-World 5-year Cohort Study

IntroductionThere is limited research in adolescent at risk for psychosis. The new criteria of Attenuated Psychosis Syndrome (APS) of Diagnostic and Statistical Manual of Mental Disorders- 5 (DSM-5) have not been validated.ObjectivesThe aims of this study were to: 1) characterize adolescent’s profile with APS (DSM-5 APS) compared to adolescents with early onset psychosis (EOP) and with other psychiatric disorders (non-APS); 2) to estimate their long-term risk of transition to psychosis and prognostic accuracy of DSM-5 APS.Methods243 adolescents, aged 12-17, were included (October 2012- July 2019) and dived in three sub-groups (110 DSM-5 APS, 31 EOP, 102 non-APS). All underwent a comprehensive assessment evaluating: sociodemographic characteristics, family and personal history of any DSM-5 psychiatric disorders, psychopathological assessment and level of functioning. An annual follow-up evaluation was carried out (up to 7 years) including a clinical interview to investigate DSM-5 criteria for transition to psychosis.ResultsDSM-5 APS adolescents had on average higher comorbid disorders (2.3) and intermediate psychopathological and functioning profile between non-APS/EOP. The cumulative risk of transition at 1,2,3, 4-5 years was 13%, 17%, 24.2%, 26.8% and 26.8% in DSM-5 APS group, 0%, 0%, 3.2%, 3.2% and 3.2% in the non-APS. The 5-year prognostic accuracy of the DSM-5 APS in adolescent was adequate (Area Under the Curve=0.77) with high sensitivity (91.3%) and suboptimal specificity (63.2%).ConclusionsThe DSM-5 APS diagnosis can be used to detect help-seeking adolescents at risk of psychosis and predict their long-term outcomes, leading the way to new preventive approaches.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Neurocognitive Functioning of Adolescents with Clinical High Risk for Psychosis, other Psychiatric Symptoms, and Psychosis

IntroductionClinical High Risk of Psychosis (CHR-P) condition and the clinical validity of at-risk criteria are still little studied in child and adolescent population.ObjectivesThis study aimed to discover neurocognitive profiles of adolescents with CHR-P, compared with adolescents with psychosis and youth with other psychiatric symptoms that do not meet CHR-P criteria.MethodsWe divided 116 adolescents (12-18 years old) in three groups according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): psychosis, attenuated psychosis syndrome (APS), non-APS. Moreover, we administered Wechsler scales to assess the IQ, Wisconsin Card Sorting Test to assess abstract reasoning and flexibility, Rey-Osterrieth complex figure to assess planning and attention, and Trail Making Test to assess psychomotor speed, visual attention and task switching. We administered BVN 12-18 subtests to assess lexical denomination, verbal and nonverbal working memory, selective auditory, visual attention, phonemic and categorial fluency, reasoning and problem solving.ResultsNineteen adolescents met criteria for psychosis, 47 for APS, and 50 did not meet criteria neither for psychosis nor for APS. APS group performed better than psychosis group and similar to non-APS group in processing speed, planning, visual attention, and categorial fluency. APS did not show a significant difference from the other groups in working memory and backward digit span, showing an intermediate profile; non-APS and psychosis groups still differed significantly in these functions.ConclusionsIdentifying typical neurocognitive profiles leads to more accurate diagnoses and early intervention that can lead to better patient outcomes.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Clinical Feasibility of Speech Phenotyping for Remote Assessment of Neurodegenerative and Psychiatric Disorders (RHAPSODY): a study protocol

IntroductionThe diagnosis of neurodegenerative and psychiatric disorders (NPDs) in primary care can suffer from inefficiencies resulting in misdiagnoses and delayed diagnosis, limiting effective treatment options. The development of speech and language-based profiling biomarkers could aid in achieving earlier motor diagnosis for PD for instance, or more accurate diagnosis of clinically similar or late presenting NPDs.ObjectivesRHAPSODY aims to investigate the feasibility of the remote administration of a battery of speech tasks in eliciting continuous narrative speech across a range of NPDs. The project also aims to determine the feasibility of using acoustic and linguistic biomarkers from speech data to support the clinical assessment and disambiguation of common NPDsMethodsAll participants (n=250) will take part in a single virtual telemedicine video conference with a researcher in which they are screened and complete a battery of speech tasks, in addition to cohort-specific screening measures. Over the following month, participants will be asked to complete a series of short, self-administered speech assessments via a smartphone application.ResultsThe speech tasks will be audio-recorded and analysed on Novoic’s technology platform. Objectives will be analysed using measures including average length of speech elicitation for speech tasks, intra- and inter-subject variance, differences in linguistic patterns, and response rates to speech assessments.ConclusionsThe analyses could help to identify and validate speech-derived clinical biomarkers to support clinicians in detecting and disambiguating between NPDs with heterogeneous presentations. This should further support earlier intervention, improved treatment options and improved quality of life.DisclosureIn terms of significant financial interest and relationships, it is emphasised that the private organisation Novoic, who aim to develop speech algorithms for diagnostic use, is the study’s sponsor and employees or former employees of this company comprise

Comparison of Wire and Disc Leads to Activate the Inspiratory Muscles in Dogs

ObjectiveHF‐SCS is a unique method of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury (SCI). The purpose of the present study was to examine the effectiveness of wire leads, which can be placed using minimally invasive techniques, to activate the inspiratory muscles.MethodsIn 5 anesthetized dogs, in separate trials, disc and wire leads were inserted onto the ventral epidural space at the T1–T4 spinal cord levels. The effects of electrical stimulation with disc, single wire, and two wire leads placed in parallel were compared.Outcome measuresAirway pressure generation following stimulation with disc and various configurations of wire leads were compared.ResultsSeveral different configurations of wire leads resulted in airway pressures that were similar to those generated with monopolar stimulation with disc leads (D). For example, monopolar stimulation (3mA, 300Hz, 0.2ms) with parallel wire leads in which each of the electrode contacts at the T2 were connected together and functioned as a common cathode (Y‐connection) and monopolar stimulation (separate cathode) at T2 both with a remote ground resulted in airway pressures that were 91±6 and 92±4%, respectively, of those achieved with D (NS for both). Bipolar stimulation (3mA, 300Hz, 0.2ms) with parallel wire leads using Y‐connection and with a separate cathode at the T2 and T3 level resulted in airway pressures that were 96 ± 4 and 94 ± 4%, respectively, of the pressures achieved with D (NS for both).ConclusionThese results suggest that specific configurations of wire leads, which can be placed via minimally invasive techniques, result in comparable activation of the inspiratory muscles compared to disc leads and may be a useful technique to restore ventilatory support in persons with SCI.Support or Funding InformationSupportNIH‐NINDS (R01NS064157)DisclosureDr. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems and holds patents for spinal cord stimulation to restore cough and respiration (5,678,535; 5,911,218; 5,999,855; 8,751,004). Drs. DiMarco and Kowalski hold the U.S. patents for technology related to the content of this manuscript: Respiratory Muscle Activation by Spinal Cord Stimulation (8,352,036).

A Computational Model of Upper Thoracic High‐Frequency Spinal Cord Stimulation to Optimize Inspiratory Muscle Activation

BackgroundHigh‐frequency spinal cord stimulation (HFSCS) has been previously shown to elicit physiological activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways in canines. It was previously hypothesized that during upper thoracic HF‐SCS, the phrenic motoneuron pools are activated via spinal pathways located in the ventro‐lateral funiculus (VLF).ObjectiveThe aim of the present study was to develop a computational model of ventral HFSCS to optimize stimulation parameters and electrode configurations for activation of the inspiratory muscles.MethodsWe created a computer model of an anatomically‐accurate finite element model (FEM) of the canine spinal cord and surrounding anatomy, along with an implanted HFSCS electrode array. From this FEM, we calculated extracellular voltages generated by SCS and applied them to multicompartment cable models of axons within the VLF. Model analysis compared activation thresholds for several unique electrode designs, configurations, and electrode placements in order to optimize activation of these VLF fibers to maximize inspiratory muscle activation.ResultsFor initial model parameterization, we performed experimental measurements testing various electrode configurations and designs. We then used our computer model to evaluate several additional stimulation configurations (e.g. monopolar, bipolar) on VLF fiber selectivity. We then evaluated the effect of wider or narrow lateral lead spacing, contact spacing, and contact size. Finally, we considered several SCS waveform settings, such as rectangular waveforms and ramped waveforms, to potentially generate muscle activation more similar to natural inspiration.ConclusionsWe used our model to optimize electrode configurations, placements and novel stimulation waveforms of HFSCS to target fibers within the VLF. In particular, we found that wider lateral spacing between percutaneous electrodes better targets VLF fibers as opposed to the narrower spacing initially tested. We also show that ramped stimulation slowly recruits VLF fibers over time, which could improve naturalistic inspiratory muscle activation. In future work, we will perform experimental measurements in an animal model of HFSCS to confirm the ability of these optimized electrode designs and waveform parameters to better recreate normal inspiration.DisclosureDr. DiMarco is a founder of and has a significant financial interest in Synapse BioMedical, a manufacturer of diaphragm pacing systems and holds patents for spinal cord stimulation to restore cough and respiration (5,678,535; 5,911,218; 5,999,855; 8,751,004). Drs. DiMarco and Kowalski hold the U.S. patents for technology related to the content of this manuscript: Respiratory Muscle Activation by Spinal Cord Stimulation (8,352,036).Support or Funding InformationThis work is supported by NIH‐NINDS (R01NS064157).

Industry payments to physician journal editors.

BackgroundOpen Payments is a United States federal program mandating reporting of medical industry payments to physicians, increasing transparency of physician conflicts of interest (COI). Study objectives were to assess industry payments to physician-editors, and to compare their financial COI rate to all physicians within the specialty.Methods and findingsWe performed a retrospective analysis of prospectively collected data, reviewing Open Payments from August 1, 2013 to December 31, 2016. We reviewed general payments (“… not made in connection with a research agreement”) and research funding to “top tier” physician-editors of highly-cited medical journals. We compared payments to physician-editors and physicians-by-specialty. In 35 journals, 333 (74.5%) of 447 “top tier” US-based editors met inclusion criteria. Of these, 212 (63.7%) received industry-associated payments in the study period. In an average year, 141 (42.3%) of physician-editors received any direct payments to themselves including general payments and research payments, 66 (19.8%) received direct payments >$5,000 (National Institutes of Health threshold for a Significant Financial Interest) and 51 (15.3%) received >$10,000. Mean annual general payments to physician-editors was $55,157 (median 3,512, standard deviation 561,885, range 10–10,981,153). Median general payments to physician-editors were mostly higher compared to all physicians within their specialty. Mean annual direct research payment to the physician-editor was $14,558 (median 4,000, range 15–174,440). Mean annual indirect research funding to the physician-editor’s institution (highly valued by academic leaders such as departmental chairs and deans) was $175,282 (median 49,107, range 0.18–5,000,000). The main study limitation was difficulty identifying physician-editors primarily responsible for making manuscript decisions.ConclusionsA substantial minority of physician-editors receive payments from industry within any given year, sometimes quite large. Most editors received payment of some kind during the four-year study period. Given the extent of editors’ influences on the medical literature, more robust and accessible editor financial COI declarations are recommended.

Phrenic‐to‐Intercostal Reflex Activity in Response to High Frequency Spinal Cord Stimulation (HF‐SCS)

ObjectiveHF‐SCS is a novel technique of inspiratory muscle activation which results in coincident activation of the diaphragm and inspiratory intercostal muscles via spinal cord pathways and has the potential to provide respiratory support in ventilator dependent persons with spinal cord injury. The purpose of the present study was to examine the phrenic to intercostal reflex during HF‐SCS.MethodsIn 3 anesthetized and C2 spinalized dogs, electrical stimulation was applied via a stimulating electrode located on the ventral surface of the upper thoracic spinal cord at the T2 level before and after cervical phrenicotomy. Fine wire recording electrodes were used to assess single motor unit (SMU) activity of the external intercostal muscles before and after phrenicotomy.ResultsFollowing unilateral phrenic nerve section, mean peak SMU firing frequency of EI ipsilateral to the section was significantly greater when compared to control (15.9±0.7 vs. 12.1±0.5 Hz, p<0.05). However, mean peak SMU firing frequency of the contralateral EI was unchanged (11.1±0.4 vs. 12±0.4 Hz, NS). Section of the contralateral phrenic nerve results in significantly higher mean peak SMU firing frequency of the contralateral EI (15.9±0.7 Hz, p<0.05) when compared to before section.ConclusionThis study demonstrates that during HF‐SCS after C2 spinalization: 1) diaphragmatic afferents reflexly inhibit motor activity to the ipsilateral external intercostal muscles, and 2) the neural circuitry mediating the phrenic‐to‐intercostal reflex is preserved at a spinal level. Consequently, HF‐SCS applied to support ventilation in high tetraplegics with unilateral phrenic nerve injury may elicit increased activity of ipsilateral inspiratory intercostal muscles.Support or Funding InformationSupport: NIH‐NINDS (R01NS064157) and MetroHeath FoundationDisclosure: Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Information for authors and editorial policies

Information for authors and editorial policies

How Should Journals Handle the Conflict of Interest of Their Editors?

Conflict of interest (COI) policies at most academic medical centers require that investigators disclose research-related financial interests to their institutions so the institution can review the potential risks of the COI. To manage COI, academic medical centers typically direct investigators to disclose their financial interests to research participants and to journal editors. If an institution follows the guidelines of the Association of American Medical Colleges,1 except for situations in which a researcher has a significant financial interest in research involving humans, investigators generally are permitted to retain their financial interests while performing related research as long as there is transparency about their financial interests via disclosure to the consumers (eg, research participants, co-investigators, and individuals who receive reports of the research, including those listening to a presentation of the research or reading an article about the research).

Promoting Respiratory Motor Plasticity After Spinal Cord Injury Through High Frequency Stimulation (HF‐SCS)

More than 50% of the spinal cord injury (SCI) population have injuries at the cervical level. Located at this level are the respiratory bulbospinal pathways which mediate breathing. Therefore, injuries at the cervical level can leave many of these patients unable to breath. One promising intervention to restore breathing is HF‐SCS (300Hz). In previous investigations, we demonstrated that HF‐SCS applied at the T2 level after an experimental complete C2 spinal cord section leads to evoked inspiratory diaphragmatic EMG activity that can enable survival of the animal. However, the extent to which HF‐SCS can promote spinal respiratory motor plasticity in order to promote restoration of breathing function is still unknown. To address this question, we performed a HF‐SCS at the T2 level in six anesthetized rats while recording bilateral diaphragmatic EMG activity one week after C2 hemisection. As expected, C2 hemisection abolished activity in the hemidiaphragm ipsilateral to the hemisection, while spontaneous activity contralateral to the C2 hemisection still remained. HF‐SCS resulted in robust inspiratory activity bilaterally in the diaphragm. Following discontinuation of HF‐SCS bilateral spontaneous activity persisted. Moreover, EMG activity on the hemisected side was synchronized with the contralateral side. Taken together, these results suggest that HF‐SCS after a C2 hemisection can enhance activity and promote plasticity of the crossed phrenic pathways which still remain. Further studies are planned to explore the mechanisms of these observations with the ultimate goal to restore function in patients following SCI.Support or Funding InformationFunded by University of Kentucky College of Medicine Funds & The MetroHeath Foundation.Disclosure: Dr. DiMarco has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.

Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography

To screen for subclinical keratoconus by analyzing corneal, epithelial, and stromal thickness map patterns with Fourier-domain optical coherence tomography (OCT). Four centers in the United States. Cross-sectional observational study. Eyes of normal subjects, subclinical keratoconus eyes, and the topographically normal eye of a unilateral keratoconus patient were studied. Corneas were scanned using a 26,000 Hz Fourier-domain OCT system (RTVue). Normal subjects were divided into training and evaluation groups. Corneal, epithelial, and stromal thickness maps and derived diagnostic indices, including pattern standard deviation (PSD) variables and pachymetric map-based keratoconus risk scores, were calculated from the OCT data. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic accuracy of the indices. The study comprised 150 eyes of 83 normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1 topographically normal eye of a unilateral keratoconus patient. Subclinical keratoconus was characterized by inferotemporal thinning of the cornea, epithelium, and stroma. The PSD values for corneal (P < .001), epithelial (P < .001), and stromal (P = .049) thickness maps were all significantly higher in subclinical keratoconic eyes than in the normal group. The diagnostic accuracy was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941; epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric map-based keratoconus risk score (AUC = 0.735). High-resolution Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses. Corneal and sublayer thickness changes in subclinical keratoconus could be detected with high accuracy using PSD variables. These new diagnostic variables might be useful in the detection of early keratoconus. Oregon Health and Science University (OHSU) and Drs. Li, Tan, and Huang have a significant financial interest in Optovue, Inc. These potential conflicts have been reviewed and managed by OHSU. Dr. Brass receives research grants from Optovue, Inc. Drs. Chamberlain and Weiss have no financial or proprietary interest in any material or method mentioned.

Navigating the Murky Waters of Conflict of Interest: Searching for the Middle Path.

On August 23, 2011, the U.S. Department of Health and Human Services issued the Final Rule on conflict of interest. The purpose of the rule was to provide a clear framework for federally funded studies to identify, reduce, avoid, and/or manage researchers' external commercial relationships that could appear to impact the design, conduct, or reporting of research. Since the issuance of the final rule, colleges and universities have been tasked with closely monitoring external commercial relations of faculty to ensure that potential biases in research are minimized. The monitoring has become an even greater challenge as federal dollars for research decline, along with colleges and universities' ability to internally fund research. External commercial relations, including faculty start-up companies, are often an easy go-to source for funding to continue research and development. In such cases, sources of funding vary from crowdfunding to commercial incubator or innovation project start-up funds. There have been many lessons learned since implementation. This article will site some common examples encountered at one university of commercial relationships that have the potential to affect human subject research. Every industry tie to academically based research must be closely reviewed to ensure appropriate interactions between researchers and sponsors. Equally imperative is to build a collaborative relationship with faculty and conflict of interest administrators. Transparency and partnership are key to developing workable management plans. Even when there is the presence of a significant financial interest, much can be done to protect human subjects as well as the integrity of the research. Independent oversight, prohibiting the principal investigator (PI) from recruiting patients, limiting access to data, replication of results, review of annual progress reports, informing patients of potential financial gain, and so forth, are just a few of the safeguards we can put into place to reduce potential bias and inform and protect human subjects. Just like we need to be creative in identifying new ways of approaching research problems, we need to be creative in how we approach and manage academic and industry relationships. This creativity has the potential to benefit researchers who are exploring new frontiers, patients who may enjoy increased health, and companies with successful products on the market. Caution should be taken when generalizing to other institutions as resources available to manage will vary across organizations.

Is Conflict of Interest Becoming a Challenge for Institution-Based Institutional Review Boards?

Expansion of business relationships between academic institutions and their leaders and industry have become a reality, whereas media attention regarding conflict of interest (COI) at academic institutions has raised concerns about possible erosion of public trust. The Institutional Review Board (IRB) should collaborate with institutional COI committees to ensure that research with human subjects is in compliance with various applicable federal regulations. The IRB and COI committee should take additional independent action as necessary under their separate mandates to protect the welfare, safety, and rights of human subjects and to include limits on protocols affected by significant financial interests of the institution or its decision makers. If unable to review research due to an intrainstitutional conflict, the local IRB should consider transferring the study review and oversight to an external unaffiliated institutional or central IRB. A process for involvement of an executive institutional IRB is proposed.

WE‐E‐134‐04: Computerized Detection of Breast Cancer On Automated Breast Ultrasound for Women with Dense Breasts

Purpose. Develop a computer‐aided detection method and investigate its feasibility for detection of breast cancer in automated 3D ultrasound for women with dense breasts.Methods. The HIPAA‐compliant study involved a dataset of 3D automated breast ultrasound image volumes (views) acquired with a U‐Systems SomoV ABUS system for 185 asymptomatic women with dense breasts (BI‐RADS Composition/Density 3 or 4). For each patient, three 3D views per breast were acquired. A total of 52 patients had breast cancer (61 cancers) and 31 patients (32 cancers) had a screening‐mammogram, clinically‐assigned BI‐RADS Assessment Category 1 or 2, i.e., were mammographically negative. All software was developed in‐house and involved 3 steps: 1) detection of initial tumor candidates, 2) characterization of candidates, and 3) elimination of false‐positive detections. Performance was assessed through the cancer detection sensitivity as a function of the number of marks (detections) per view. Results. At a single mark per view, i.e., 6 marks per patient, the median detection sensitivity of our computerized method was 50.0% (16/32) for the patients with a screening mammogram assigned BI‐RADS category 1 or 2, similar to the 49.9% on average obtained for these by patients by 17 radiologists in a reader study. At 3 marks per view, the sensitivity was 69% (22/32)+/−5% for the BI‐RADS 1 and 2 patients, and 64% (39/61)+/−3% for all patients.Conclusion. Promising detection sensitivity was obtained for this 3D ultrasound dataset of women with dense breasts at a rate of false‐positive detections that may be feasible for clinical implementation. Conflict of interest statement: M.L.G. is a stockholder in R2 Technology/Hologic and receives royalties from Hologic, GE Medical Systems, MEDIAN Technologies, Riverain Medical, Mitsubishi and Toshiba. K.D. received royalties from Hologic. It is the University of Chicago Conflict of Interest Policy that investigators disclose publicly actual or potential significant financial interest that would reasonably appear to be directly and significantly affected by the research activities. Funding: This work was supported in part by NIH S10 RR021039 and P30 CA14599. and the Department of Radiology of the University of Chicago