Understanding Successful Mentor-Mentee Relationships in New Faculty Scholars Program.

Background and Objectives: Mentorship is critical for the career development of health care professionals and educators. Facilitating successful mentorship is valuable in supporting future leaders and educators in family medicine. Since 1988, the Society of Teachers of Family Medicine's New Faculty Scholars (NFS) program has provided 1-year mentorship opportunities for new faculty. This qualitative study used group concept mapping to identify the characteristics of successful mentorship relationships within the NFS program. Methods: Eight New Faculty Scholars (five mentors, three mentees) from 2015 to 2021 participated in a virtual 90-minute group concept-mapping and pattern-matching session. Participants generated statements in response to a prompt about successful features of mentorship relationships. Participants categorized responses by similarity and rated each statement on a numerical scale from 1 to 5 (1 indicating lowest, 5 indicating highest) according to importance, current presence within the program, and feasibility. Results: Statements generated by participants were grouped into seven common themes. Categories rated most important included interpersonal skills, mentor soft skills, and mentor preparation. Structured processes and goal setting, mentor soft skills, and mentor preparation were rated most feasible in terms of future improvement. Conclusions: Interpersonal skills, mentor soft skills, and mentor preparation were the most highly rated by participants, but also displayed the largest disparity when compared to ratings on current presence. Future efforts to improve interpersonal communication and mentor training can potentially lead to greater satisfaction with the NFS program. The most highly rated categories indicated the primary benefit of the relational components of mentorship.

Preparing fertile ground: how does the quality of business environments affect MSE growth?

We study how the quality of local business environments helps explain growth outcomes of micro- and small enterprise microfinance clients by drawing on long-term nationwide administrative data and a policy shock in Cambodia. The staggered launch of special economic zones, which we link to positive shocks to the business environment on both the demand and supply side, leads to significantly increased employment in micro- and small enterprises (MSEs) located in these special economic zones (SEZs), compared to enterprises in contextually similar districts that are unexposed to an SEZ. Key channels explaining the improved growth outcomes include expanded access to external markets for the enterprises' goods and services, more dynamic labor environments, and improved credit terms and conditions. To broaden the relevance of our findings, we combine data from prominent empirical studies on microfinance and demonstrate how related business conditions identified in the enterprise growth literature help explain differences in client business outcomes found in their results. Policy implications are that a smaller but influential segment of microfinance borrowers significantly benefit from opportunities provided by improved local business environments and that governments and lenders can play active roles in facilitating the necessary improvements for such MSEs.

Financial access may not be fulfilling its real potential in low-income settings, unless coupled with the right opportunities in the business environment for micro- and small enterprises. We use Cambodia's special economic zones as a policy shock to study how the quality of local business environments help explain micro- and small enterprise microfinance clients' growth. We find that the SEZs generate large increases in employment for microfinance borrowers for both micro- and small enterprises. These increases are concentrated in locations where SEZs expand access to local markets and where there are more dynamic labor environments. The SEZs also lead the microfinance lender to improve credit terms, which contribute notably to improved enterprise outcomes. To broaden the relevance of our findings, we demonstrate how related sub-national business environment factors help explain different borrower outcomes found in extant studies that measure microfinance impacts. Policy implications are that an important subset of microfinance borrowers is able to seize opportunities provided by local business environments, and that national and subnational governments can play active roles in facilitating such improved business environments for micro and small enterprises.

Highly mismatch-tolerant homology testing by RecA could explain how homology length affects recombination.

In E. coli, double strand breaks (DSBs) are resected and loaded with RecA protein. The genome is then rapidly searched for a sequence that is homologous to the DNA flanking the DSB. Mismatches in homologous partners are rare, suggesting that RecA should rapidly reject mismatched recombination products; however, this is not the case. Decades of work have shown that long lasting recombination products can include many mismatches. In this work, we show that in vitro RecA forms readily observable recombination products when 16% of the bases in the product are mismatched. We also consider various theoretical models of mismatch-tolerant homology testing. The models test homology by comparing the sequences of Ltest bases in two single-stranded DNAs (ssDNA) from the same genome. If the two sequences pass the homology test, the pairing between the two ssDNA becomes permanent. Stringency is the fraction of permanent pairings that join ssDNA from the same positions in the genome. We applied the models to both randomly generated genomes and bacterial genomes. For both randomly generated genomes and bacterial genomes, the models show that if no mismatches are accepted stringency is ∼ 99% when Ltest = 14 bp. For randomly generated genomes, stringency decreases with increasing mismatch tolerance, and stringency improves with increasing Ltest. In contrast, in bacterial genomes when Ltest ∼ 75 bp, stringency is ∼ 99% for both mismatch-intolerant and mismatch-tolerant homology testing. Furthermore, increasing Ltest does not improve stringency because most incorrect pairings join different copies of repeats. In sum, for bacterial genomes highly mismatch tolerant homology testing of 75 bp provides the same stringency as homology testing that rejects all mismatches and testing more than ∼75 base pairs is not useful. Interestingly, in vivo commitment to recombination typically requires homology testing of ∼ 75 bp, consistent with highly mismatch intolerant testing.

Pharmacotherapy for Spine-Related Pain in Older Adults.

As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.

Acetaminophen (paracetamol) is safe in older adults, but non-steroidal anti-inflammatories (e.g. ibuprofen) may be more effective for spine-related pain. Non-steroidal anti-inflammatories should be used in short-term lower dose courses with gastrointestinal precaution. Corticosteroids have the least evidence for treating nonspecific back pain. Gabapentin and pregabalin may cause dizziness or difficulty walking, but may have some benefit for neck and back nerve pain (e.g. sciatica) in older adults. They should be used in lower doses with smaller dose adjustments. Some muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are avoided in older adults due to risk for sedation and falls. Others (tizanidine, baclofen, dantrolene) may be helpful for neck and back pain, with the most evidence for tizanidine and baclofen. These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease. Older antidepressants are typically avoided in older adults due to their side effects, but nortriptyline and desipramine may be better tolerated for neck and back nerve pain at lower doses. Overall, newer antidepressants (namely duloxetine) have a better safety profile and good efficacy for spine-related nerve pain. Tramadol may be tolerated in older adults, but has risk for sedation, upset stomach, and constipation. It may be used in lower doses after alternative medications have failed, and works well with co-administered acetaminophen. Opioids are avoided due to their side effects and mortality risk, but low-dose opioid therapy may be helpful for severe refractory pain with close monitoring of patients clinically.

Dynamically Mapping Socket Loading Conditions During Real Time Operation of an Upper Limb Prosthesis.

A continuing problem faced by amputees is that extended use of a prosthesis leads to discomfort along the residual limb. In this work, we use a novel pressure sensor array and an inertial measuring unit to monitor the changes in the pressure distribution within an upper limb socket in response to its position and the real time performance of a grasping task. These experiments illustrate that the operation of a prosthetic hand produces distinct features in the time derivative and spatial component of the sensor outputs, which correspond to the orientation and task-dependent changes in loading conditions within the socket. The significance of this study is that it highlights the use of a combined pressure sensor array and inertial measuring unit as a way to characterize the loading conditions within a prosthesis based on both temporal and spatial information during movement. This method of real time pressure sensing in prosthetic sockets will be useful for adaptive socket technology aimed towards decreasing the discomfort caused by long-term use of a prosthesis.

Performance Assessment of a Custom, Portable, and Low-Cost Brain-Computer Interface Platform.

OBJECTIVE: Conventional brain-computer interfaces (BCIs) are often expensive, complex to operate, and lack portability, which confines their use to laboratory settings. Portable, inexpensive BCIs can mitigate these problems, but it remains unclear whether their low-cost design compromises their performance. Therefore, we developed a portable, low-cost BCI and compared its performance to that of a conventional BCI. METHODS: The BCI was assembled by integrating a custom electroencephalogram (EEG) amplifier with an open-source microcontroller and a touchscreen. The function of the amplifier was first validated against a commercial bioamplifier, followed by a head-to-head comparison between the custom BCI (using four EEG channels) and a conventional 32-channel BCI. Specifically, five able-bodied subjects were cued to alternate between hand opening/closing and remaining motionless while the BCI decoded their movement state in real time and provided visual feedback through a light emitting diode. Subjects repeated the above task for a total of 10 trials, and were unaware of which system was being used. The performance in each trial was defined as the temporal correlation between the cues and the decoded states. RESULTS: The EEG data simultaneously acquired with the custom and commercial amplifiers were visually similar and highly correlated ( ρ = 0.79). The decoding performances of the custom and conventional BCIs averaged across trials and subjects were 0.70 ± 0.12 and 0.68 ± 0.10, respectively, and were not significantly different. CONCLUSION: The performance of our portable, low-cost BCI is comparable to that of the conventional BCIs. SIGNIFICANCE: Platforms, such as the one developed here, are suitable for BCI applications outside of a laboratory.

Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency.

The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC50s) of ∼50 nM, and three others have submicromolar IC50s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [14C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.

Recognition and Knowledge of Medications with Black Box Warnings Among Pediatricians and Emergency Physicians.

"Boxed warnings" (BW), sometimes referred to as "black box warnings," are the most serious level of warning provided by the Food and Drug Administration (FDA). We aimed to assess physician awareness and knowledge of BW, and to gain a better understanding of where physicians obtain information about serious adverse drug reactions for commonly prescribed medications. A cross-sectional survey instrument was administered to emergency medicine (EM) and pediatrician (Peds) attending and resident physicians. The main outcome measures were physician performance in identifying medications with and without black box warnings and the content of the warnings. The survey response rate was 81/198 (41 %). Respondents correctly identified medications with BW only 36.3 % of the time, but were able to correctly identify medications without such warnings 83.8 % of the time. Attending physicians were better able to identify medications with or without BW when compared with residents (p < 0.05). Among residents, there was a statistically significant increase in the ability to identify medications with or without BW with increasing year of training (p < 0.01). Correct identification of the content of BW was low in both groups (13.3 %). Only 19/50 (37 %) EM physicians and 16/31 (52 %) Peds reported that they consider BW when prescribing medications. 23/81 (29 %) respondents indicated that they did not stay current or had no method of staying current with black box information. EM and Peds attending and resident physicians at a single institution had limited ability to identify medications containing BW or the content of such warnings. A significant number reported that they did not stay current or had no consistent method for staying current with BW.

The impact of state level graduated driver licensing programs on rates of passenger restraint use and unlicensed driving in fatal crashes.

Since 1996, states have been implementing and enhancing their graduated driver licensing (GDL) programs. Increased licensing restrictions could steer new drivers to bypass training and licensing altogether. Unlicensed driving is associated with increased fatal crashes and high-risk behaviors that have been shown to adversely affect passenger safety behaviors like restraint use. The objective of this study was to assess the impact of varying state level GDL programs on rates of unlicensed driving and on passenger restraint use. De-identified data from the National Highway Traffic Safety Administration's Fatality Analysis Reporting System from years 1996-2010 was analyzed. Fatal crashes involving drivers (15-24 yrs) and their passengers (15-24 yrs) were included. Using a validated system, each state's GDL laws at a given month were rated as poor, marginal, fair, or good. The association between GDL strength and unlicensed driving was analyzed graphically and by chi-square test. Multivariate logistic regression with generalized estimating equations were undertaken to assess the relationship between GDL strength and passenger restraint use. From January 1996 to December 2010, 26,504 (23.4%) passengers were involved in fatal crashes taking place in states with GDL programs rated poor, 21,366(18.9%) marginal, 33,603 (29.6%) fair, and 31,903 (28.1%) good. Rates of unlicensed driving ranged from 16.4% in state-months rated marginal versus 21.5% in state-months rated good (p<0.001). In the multivariate model, compared to states with poor GDL ratings, each additional rating boost was associated with an increased odds of passenger safety restraint use (OR 1.15, 95% CI 1.13-1.18). Our findings suggest that stronger GDL law can mitigate passenger risk in fatal crashes by encouraging passenger restraint use. Our study provides evidence that stronger legislation in these states may reduce overall risk to young drivers and their passengers.

Young unlicensed drivers and passenger safety restraint use in u.s. Fatal crashes: concern for risk spillover effect?

Young unlicensed drivers are more likely to be in fatal crashes and to engage in high-risk driving behaviors like impaired driving, speeding, and driving unrestrained. In a crash context, the influence of these high-risk behaviors may spillover to adversely affect passenger safety restraint use. We conducted an analysis of the Fatality Analysis Reporting System from years 1996-2008. Fatal crashes involving a driver aged 15-24 years and at least one passenger aged 15-24 years were included. Logistic regression with generalized estimating equations was undertaken to assess the effect of unlicensed driving on passenger restraint use. We controlled for established predictors of passenger restraint use including driver restraint use, gender, number of occupants, driver drinking, number of occupants, crash year, and crash location (rural vs. urban). 102,092 passengers were involved in fatal crashes during the time period with 64,803 unique drivers. 6,732 (10.51%) were never licensed drivers and 5,603 (8.8%) were drivers with suspended, revoked, or expired licenses. Rates of unlicensed driving ranged from 17.7% to 22.1% and increased over time. While passengers in fatal crashes averaged a mere 40.9% restraint use, passengers of never and invalidly licensed drivers had a further decreased odds of wearing a safety restraint (OR 0.73, 95% CI 0.69-0.77, p<0.001) and (OR 0.84, 95% CI 0.79-0.90, p<0.001). Unlicensed driving is involved in a disproportionate and increasing number of preventable crash fatalities and plays a detrimental role in the lifesaving safety behaviors of their passengers. Our findings highlight an alarming peer influence between unlicensed drivers and passengers, placing increased emphasis on the need to better understand and characterize this present and growing threat.

Ectodomain cleavage of the EGF ligands HB-EGF, neuregulin1-beta, and TGF-alpha is specifically triggered by different stimuli and involves different PKC isoenzymes.

Metalloproteinase cleavage of transmembrane proteins (ectodomain cleavage), including the epidermal growth factor (EGF) ligands heparin-binding EGF-like growth factor (HB-EGF), neuregulin (NRG), and transforming growth factor-alpha (TGF-alpha), is important in many cellular signaling pathways and is disregulated in many diseases. It is largely unknown how physiological stimuli of ectodomain cleavage--hypertonic stress, phorbol ester, or activation of G-protein-coupled receptors [e.g., by lysophosphatidic acid (LPA)]--are molecularly connected to metalloproteinase activation. To study this question, we developed a fluorescence-activated cell sorting (FACS)- based assay that measures cleavage of EGF ligands in single living cells. EGF ligands expressed in mouse lung epithelial cells are differentially and specifically cleaved depending on the stimulus. Inhibition of protein kinase C (PKC) isoenzymes or metalloproteinase inhibition by batimastat (BB94) showed that different regulatory signals are used by different stimuli and EGF substrates, suggesting differential effects that act on the substrate, the metalloproteinase, or both. For example, hypertonic stress led to strong cleavage of HB-EGF and NRG but only moderate cleavage of TGF-alpha. HB-EGF, NRG, and TGF-alpha cleavage was not dependent on PKC, and only HB-EGF and NRG cleavage were inhibited by BB94. In contrast, phorbol 12-myristate-13-acetate (TPA) -induced cleavage of HB-EGF, NRG, and TGF-alpha was dependent on PKC and sensitive to BB94 inhibition. LPA led to significant cleavage of only NRG and TGF-alpha and was inhibited by BB94; only LPA-induced NRG cleavage required PKC. Surprisingly, specific inhibition of atypical PKCs zeta and iota [not activated by diacylglycerol (DAG) and calcium] significantly enhanced TPA-induced NRG cleavage. Employed in a high-throughput cloning strategy, our cleavage assay should allow the identification of candidate proteins involved in signal transduction of different extracellular stimuli into ectodomain cleavage.