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There is substantial evidence of the connection between career development and mental health. Executive processing, including associated feelings and thoughts, has been found to significantly impact career decision making and problem solving. This has implications for career practitioners tasked with addressing these complex concerns. Utilizing comprehensive frameworks that account for this connection is essential. Cognitive Information Processing theory (CIP; Sampson et al., 2020; Sampson et al., 2004) accounts for the interconnected elements of career and mental health, and specific dimensions of executive processing. Interventions derived from CIP as well as other approaches offer a structure in which to address executive processing elements influencing career development. Being intentional in assessing and addressing career-related thoughts and feelings enables a career practitioner to effectively and efficiently support those in need.

Anxiety and depression have increased exponentially and can be exacerbated by the ongoing individual and combined effects of the pandemic, ongoing unemployment, and systemic racism. Across the globe, career counsellors see the impact of these mental health concerns on individuals as they engage in career-decision making and problem-solving. Cognitive Information Processing theory (CIP; Sampson et al., 2020) can provide a useful framework for supporting diverse individuals experiencing heightened mental health and career concerns. In this article, we review key components of CIP theory, provide specific case examples that highlight the integration of career and mental health, and offer CIP-based conceptualizations and interventions.

High-energy pelvic ring injuries are associated with a significant rate of mortality and may require urgent stabilization with anterior pelvic external fixation. The iliac crest can be used for pin placement, but supra-acetabular pin placement is biomechanically superior. Traditionally, supra-acetabular pin placement is performed in the operating room, with time-consuming imaging techniques. However, because of the implicit high-energy nature of these injuries, patient physiology may prevent transport to the operating room and preclude the use of tedious image-guided techniques. Here, we describe a technique that can be performed at the bedside and without image guidance. [ Orthopedics . 2022;45(5):e284–e287.]

This study sought to postoperatively compare femoral cortical button (FCB) placement in anterior cruciate ligament (ACL) reconstruction performed using an adjustable loop cortical femoral fixation button under direct arthroscopic visualization vs indirect methods. The authors conducted a retrospective review of postoperative knee radiographs from 76 patients who had undergone ACL reconstruction with an adjustable loop cortical femoral fixation button. Operative reports were reviewed to determine the technique used for graft placement. Two sports fellowship–trained surgeons reviewed the collected radiographs, and the position of the FCB in each patient was subsequently graded. Of the 76 patients reviewed, 42 cases were performed using direct visualization, whereas 34 cases used indirect methods. This analysis showed that FCBs placed with direct visualization were more likely to have optimal position directly on the femoral cortex compared with indirect methods (chi-square test, P =.046). The grading scores demonstrated moderate strength of interobserver reliability (kappa coefficient=0.62). Direct arthroscopic visualization while placing an FCB during ACL reconstruction with an adjustable loop cortical fixation button can help ensure optimal button placement. [ Orthopedics . 2020;43(3):191–195.]

New-onset atrial fibrillation (AF) during COVID-19 infection is associated with worse cardiovascular outcomes and mortality, with new-onset AF being associated with worse clinical outcomes than recurrent AF. However, it is not known whether a prior history of AF is an independent cardiovascular risk factor predicting worse outcomes in COVID-19 patients. The present investigation sought to determine whether AF should be considered a risk factor for worse outcomes in COVID-19 illness.From March 2020-September 2021 patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n = 3623) were propensity matched to non-AF SARS-CoV-2 positive patients (n = 3610). Multivariable Cox hazard regression was used to determine subsequent MACE (all-cause death, myocardial infarction, HF and stroke) risk among patients with and without AF.COVID-19 patients with a prior history of AF were more likely to be hospitalized, require ICU care, supplemental oxygen, and ventilator support compared COVID-19 patients without a history of AF. There was a 1.40 times higher rate of MACE in the COVID-19 patients with prior AF compared to patients without prior AF (AF history was shown to be an independent risk factor for MACE during a COVID-19 illness. Both recurrent and principally new-onset AF were associated with an increased risk of poor clinical outcomes during COVID-19 illness.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet the genetic cause of up to 50% of cases remains unknown. Here, we show that mutations in KLHL24 cause HCM in humans. Using genome-wide linkage analysis and exome sequencing, we identified homozygous mutations in KLHL24 in two consanguineous families with HCM. Of the 11 young affected adults identified, 3 died suddenly and 1 had a cardiac transplant due to heart failure. KLHL24 is a member of the Kelch-like protein family, which acts as substrate-specific adaptors to Cullin E3 ubiquitin ligases. Endomyocardial and skeletal muscle biopsies from affected individuals of both families demonstrated characteristic alterations, including accumulation of desmin intermediate filaments. Knock-down of the zebrafish homologue klhl24a results in heart defects similar to that described for other HCM-linked genes providing additional support for KLHL24 as a HCM-associated gene. Our findings reveal a crucial role for KLHL24 in cardiac development and function.

The fixation of posterior wall acetabular fractures often utilizes interfragmentary screws with varying length. Intricate pelvic anatomy and overhanging greater trochanter make obtaining proper screw trajectory difficult. A large measurement may represent aberrant trajectory and breach of the articular surface. This study aims to identify a preferred maximum screw length that avoids intra-articular penetration.We hypothesized that a screw measured 40 millimeters or longer has a high likelihood of being intra-articular.A retrospective review included CT scans of 151 consecutive patients collected at a level-1 trauma center was analyzed by two observers. On axial imaging, a straight line was measured at the largest extraarticular portion of the posterior wall simulating ideal screw placement. Another line was measured tangent to the articular surface simulating longest possible extraarticular screw. Measurements were taken at 2-millimeter increments.The intra-class correlation coefficient between both observers was excellent (0.75-1.00) for most recorded values. The maximum mean length for straight line measured (m=32.18mm, SD=3.74) which was smaller than the mean length for tangent line (m=38.44, SD=4.29). Exploratory multivariate logistic regression analyses demonstrated increased height, age, and acetabular version were associated with larger measurements greater than 40mm (p0.05).This study demonstrates that most acetabular posterior walls cannot accommodate a 40 millimeter lag screw. If the measured drill hole is greater than this length, then careful reconsideration of the screw trajectory is warranted to ensure the screw is not intra-articular. Older and taller patients may be able to accommodate longer screws.III.

Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence.SUMMARYThis study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.

The COVID-19 pandemic has had a world-wide impact on all areas of individuals' health, including physical, psychological, financial, familial, social, and vocational. In the United States, the unemployment rate rose from 3.5% (5.8 million) to 13.3% (21 million) in May 2020 before dropping to 7.9% in October 2020. Cognitive information processing (CIP)is one career theory that addresses career needs of clients and society. In this article, we examine the impact of COVID-19 on mental health and wellness, highlight differences for marginalized groups, and demonstrate how CIP theoretical elements may have been impacted by COVID-19, and provide strategies enhancing client growth in these domains during a time when largescale social and physical distancing is recommended. The CIP-based differentiated service delivery model is also described as a means for extending and providing access to career services.

Background:. Periprosthetic joint infection remains a devastating complication of total joint arthroplasty (TJA). The literature suggests that unnecessary operating room (OR) traffic increases the risk of surgical site infection by increasing bacterial load in the OR. We attempted to determine whether the posting of “restricted access” signs on the outside and inside of OR doors during primary TJA procedures would result in a reduction of OR door openings. Methods:. This prospectively designed, 2-phase study investigated the number of door openings per case for primary TJA. An independent observer collected data for each TJA case; the OR staff were blinded to the data collection to avoid bias. The first phase of this study recorded OR traffic without the use of “restricted access” signs. In the second, interventional phase of the study, OR traffic was monitored with the concomitant application of “restricted access” signs on the doors. The number of openings per case, from the time of incision to the time of dressing application, was collected. Results:. The average number of openings per case during the first phase was 75, with 0.59 door openings per minute. The average number of openings per case during the second phase was 40, with 0.28 door openings per minute. Therefore, a 47% reduction in openings per case and a 53% reduction in the number of openings per minute during primary TJA cases were observed. Conclusions:. We demonstrated that the simple addition of “restricted access” signs on the outside and inside of OR doors produced a significant reduction (p < 0.001) in OR traffic during primary TJA. Clinical Relevance:. Posting signs can decrease door openings, potentially decreasing infection.

The primary purpose of this paper is to introduce essential elements of cognitive information processing (CIP) theory, research, and practice as they existed at the time of this writing. The introduction that follows describes the nature of career choices and career interventions, and the integration of theory, research, and practice. After the introduction, the paper continues with three main sections that include CIP theory related to vocational behavior, research related to vocational behavior and career intervention, and CIP theory related to career interventions. The first main section describes CIP theory, including the evolution of CIP theory, the nature of career problems, theoretical assumptions, the pyramid of information processing domains, the CASVE Cycle, and the use of the pyramid and CASVE cycle. The second main section describes CIP theory-based research in examining vocational behavior and establishing evidence-based practice for CIP theory-based career interventions. The third main section describes CIP theory related to career intervention practice, including theoretical assumptions, readiness for career decision making, readiness for career intervention, the differentiated service delivery model, and critical ingredients of career interventions. The paper concludes with regularly updated sources of information on CIP theory.

Skeletal muscle derives from dorsal mesoderm formed during vertebrate gastrulation. Fibroblast growth factor (Fgf) signalling cooperates with Tbx transcription factors to promote dorsal mesoderm formation, but their role in myogenesis has been unclear. Using zebrafish, we show that dorsally derived Fgf signals act through Tbx16 and Tbxta to induce slow and fast trunk muscle precursors at distinct dorsoventral positions. Tbx16 binds to and directly activates the myf5 and myod genes, which are required for commitment to myogenesis. Tbx16 activity depends on Fgf signalling from the organiser. In contrast, Tbxta is not required for myf5 expression, but binds a specific site upstream of myod that is not bound by Tbx16 and drives (dependent on Fgf signals) myod expression in adaxial slow precursors, thereby initiating trunk myogenesis. After gastrulation, when similar muscle cell populations in the post-anal tail are generated from tailbud, declining Fgf signalling is less effective at initiating adaxial myogenesis, which is instead initiated by Hedgehog signalling from the notochord. Our findings suggest a hypothesis for ancestral vertebrate trunk myogenic patterning and how it was co-opted during tail evolution to generate similar muscle by new mechanisms. This article has an associated ‘The people behind the papers’ interview., Highlighted Article: Tbx16 and Tbxta activate myf5 and myod directly during the earliest myogenesis in zebrafish, and Fgf signalling acts through Tbx16 to drive myogenesis in trunk but not tail.

Cognitive information processing (CIP) theory, in existence for over four decades, boasts over 150 evidence-based articles and close to 300 manuscripts in total that demonstrate its strength as a theory, fertile opportunity for research, and utility in practice across various settings and populations. In this manuscript, the authors will present the key components of CIP, summarize empirical evidence for the validity of the theory, and describe its applications in different settings. To demonstrate the differentiated model of career service delivery, two brief case scenarios will be provided.

As the distinction between the digital and physical worlds continues to diminish, the necessity to reevaluate the bargain struck by the copyright regime increases in importance. Digitization brings increasingly more aspects of our world into the potential ambit of the copyright system. To understand whether and how the copyright system should apply in an increasingly digital world, it is first necessary to understand doctrinally how current copyright laws apply to new digital works. This Article corrects several errors that have appeared in the literature analyzing copyright law’s treatment of 3D printing and other digital manufacturing files. This Article incorporates an advanced technical understanding of digital manufacturing files and applies that understanding to copyright doctrine to clarify misunderstandings. The analysis briefly confirms that digital files created to manufacture creative objects are themselves clearly protected by copyright. On the other hand, and contrary to several assertions in the literature, most files created to manufacture purely utilitarian objects are not copyrightable because they lack a modicum of creativity. The lack of copyright protection for these files calls into question a number of assumptions, including whether they can be protected against even verbatim copying and whether open-source licenses involving these files can efficaciously bind downstream users. If digital manufacturing files of purely utilitarian objects do not enjoy copyright protection, creators may seek to embed additional, ancillary copyrightable material in the files to secure protection. This ancillary material serves as a lock-out code, which tries to prevent what would otherwise be lawful copying. This Article analyzes that phenomenon and discusses potential ways the law may react to it.

Background Long-term outcomes after direct current cardioversion (DCCV) in patients that receive anticoagulation have demonstrated to have no adverse sequela. Less is known about the impact on atrial fibrillation (AF) outcomes and resource utilization of repeated DCCVs that are often required for long-term rhythm control. Methods A total of 4,135 AF patients >18 years of age that underwent DCCV with long-term system follow-up were evaluated. Patients were stratified by the number of DCCVs received: 1 (n=2,201), 2-4 (n=1,748), and ≥5 (n=186). Multivariable Cox hazard regression was used to determine the association of DCCV categories to the outcomes of death, AF hospitalization, AF ablation, DCCVs, and stroke/transient ischemic attack. Results The average follow-up of the patient population was 1,633.1±1,232.9 (median: 1,438.0) days. Patients who underwent 2-4 and ≥5 DCCVs had more comorbidities, namely hypertension, hyperlipidemia and heart failure. Anticoagulation use was common at the time of DCCV in all groups (89.1%, 91.2%, 91.9%, p=0.06) and amiodarone use increased with increasing DCCV category (30.1%, 43.4%, 52.2, p 5 vs. 1, (HR=1.32 [0.89-1.94], p=0.17). Conclusions This study found that the increasing number of DCCVs, despite escalation of other pharmacologic and nonpharmacologic therapies, is a long-term independent risk factor for repeat DCCVs, ablations, and AF hospitalizations among AF patients.

Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Observational trials suggest that the implementation and quality of long‐term anticoagulation impact dementia risk. Emerging evidence suggests that direct oral anticoagulants may improve long‐term risk of dementia in AF patients. This manuscript describes the rational and trial design of the the Cognitive Decline and Dementia in Atrial Fibrillation Patients (CAF) Trial. CAF investigates if AF patients randomized to dabigatran etexilate will have long‐term higher cognition scores and lower rates of dementia compared in the long term to dose‐adjusted warfarin (International Normalized Ratio [INR]: 2.0‐3.0). As of 27 February 2019, a total of 120 subjects will be enrolled at one investigational site in the United States and will be followed for 2 years after study enrollment. To date, 97 have been enrolled. The average age is 74.2 years, 53% are male, and 9% had a prior stroke. In this Vanguard study, patients will be followed for 2 years after study enrollment. These prospective, randomized data will inform the understanding of two anticoagulants in AF patients as it relates to risk of cognitive decline and dementia. Cranial imaging and biomarkers collected will assist in understanding mechanisms of brain injury.

Elevations of intracellular free Ca2+ concentration ([Ca2+]i) are a potent trigger for Weibel-Palade body (WPB) exocytosis and secretion of Von Willebrand factor (VWF) from endothelial cells, however, the identity of WPB-associated Ca2+-sensors involved in transducing acute increases in [Ca2+]i into granule exocytosis remain unknown. Here we show that synaptotagmin 5 (SYT5) is expressed in human umbilical vein endothelial cells (HUVEC) and is recruited to WPBs to regulate Ca2+-driven WPB exocytosis. Western blot analysis of HUVEC identified SYT5 protein, and exogenously expressed SYT5-mEGFP localized almost exclusively to WPBs. shRNA-mediated knockdown of endogenous SYT5 reduced the rate and extent of histamine-evoked WPB exocytosis and reduced secretion of the WPB cargo VWF-propeptide (VWFpp). The shSYT5-mediated reduction in histamine-evoked WPB exocytosis was prevented by expression of shRNA-resistant SYT5-mCherry. Overexpression of SYT5-EGFP increased the rate and extent of histamine-evoked WPB exocytosis, and increased secretion of VWFpp. Expression of a Ca2+-binding defective SYT5 mutant (SYT5-Asp197Ser-EGFP) mimicked depletion of endogenous SYT5. We identify SYT5 as a WPB-associated Ca2+ sensor regulating Ca2+-dependent secretion of stored mediators from vascular endothelial cells.

This article presents a study with the purpose to determine preliminary findings regarding the effect of a study abroad experience on vocational identity and career decision-making as defined by Cognitive Information Processing (CIP) theory (Sampson et al., 2004).

Comparison of Remote Magnetic Irrigated Tip Background Remote magnetic navigation (RMN) and contact force (CF) sensing technologies have been utilized in an effort to improve safety and efficacy of catheter ablation. A comparative analysis of the relative short- and long-term outcomes of AF patients has not been performed. As such, we comparatively evaluated the safety and efficacy of these technologies. Methods A total of 627 patients who underwent catheter ablation with either a manual irrigated tip catheter: (312, 49.8%) or by RMN: (315, 50.2%) were included in this single-center cohort study. Patients treated with CF (59) were analyzed separately as well. One- and 3-year endpoints included death, HF hospitalization, stroke, TIA, and atrial flutter or AF recurrence. Results Age averaged 65.1 ± 10.7 years and 64.1% male. One- and 3-year endpoints of death, HF hospitalization, stroke, TIA, and atrial flutter or AF recurrence were statistically similar between manual and RMN treated groups. Fluoroscopy times were significantly lower in the RMN group compared to the manual ablation group (8.47 ± 0.45 vs. 9.63 ± 4.06 minutes, P < 0.0001). CF guided patients had 1-year recurrence rate of AF/atrial flutter statistically identical to patients treated with RMN (36.8% vs. 38.6%; P = 1.00). Conclusion RMN results in outcomes similar to manual navigation. The addition of CF sensing catheters did not improve relative procedural outcome or safety profile in comparison to RMN guided ablation in this large observational study of AF ablation.

Background Periprosthetic joint infection remains a devastating complication of total joint arthroplasty (TJA). The literature suggests that unnecessary operating room (OR) traffic increases the risk of surgical site infection by increasing bacterial load in the OR. We attempted to determine whether the posting of "restricted access" signs on the outside and inside of OR doors during primary TJA procedures would result in a reduction of OR door openings. Methods This prospectively designed, 2-phase study investigated the number of door openings per case for primary TJA. An independent observer collected data for each TJA case; the OR staff were blinded to the data collection to avoid bias. The first phase of this study recorded OR traffic without the use of "restricted access" signs. In the second, interventional phase of the study, OR traffic was monitored with the concomitant application of "restricted access" signs on the doors. The number of openings per case, from the time of incision to the time of dressing application, was collected. Results The average number of openings per case during the first phase was 75, with 0.59 door openings per minute. The average number of openings per case during the second phase was 40, with 0.28 door openings per minute. Therefore, a 47% reduction in openings per case and a 53% reduction in the number of openings per minute during primary TJA cases were observed. Conclusions We demonstrated that the simple addition of "restricted access" signs on the outside and inside of OR doors produced a significant reduction (p < 0.001) in OR traffic during primary TJA. Clinical Relevance Posting signs can decrease door openings, potentially decreasing infection.

OBJECTIVE: Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, approximately 50% of patients with a congenital myopathy remain without a genetic diagnosis following screening of known disease genes. METHODS: We performed exome sequencing on two consanguineous probands diagnosed with a congenital myopathy and muscle biopsy showing selective atrophy/hypotrophy or absence of type II myofibres. RESULTS: We identified variants in the gene (MYL1) encoding the skeletal muscle fast-twitch specific myosin essential light chain in both probands. A homozygous essential splice acceptor variant (c.479-2A>G, predicted to result in skipping of exon 5 was identified in Proband 1, and a homozygous missense substitution (c.488T>G, p.(Met163Arg)) was identified in Proband 2. Protein modeling of the p.(Met163Arg) substitution predicted it might impede intermolecular interactions that facilitate binding to the IQ domain of myosin heavy chain, thus likely impacting on the structure and functioning of the myosin motor. MYL1 was markedly reduced in skeletal muscle from both probands, suggesting that the missense substitution likely results in an unstable protein. Knock down of myl1 in zebrafish resulted in abnormal morphology, disrupted muscle structure and impaired touch-evoked escape responses, thus confirming that skeletal muscle fast-twitch specific myosin essential light chain is critical for myofibre development and function. INTERPRETATION: Our data implicate MYL1 as a crucial protein for adequate skeletal muscle function and that MYL1 deficiency is associated with a severe congenital myopathy.

Idiopathic scoliosis (IS) is the deformation and/or abnormal curvature of the spine that develops progressively after birth. It is a very common condition, affecting approximately 4% of the general population, yet the genetic and mechanistic causes of IS are poorly understood. Turner syndrome (TS) is caused by haploinsufficiency for a subset of genes within the pseudoautosomal region (PAR) at the tip of the short arm of the X chromosome thereby defining a critical interval for TS pathogenesis. Patients with TS present with a number of clinical features that individually represent common diseases, including an increased risk of developing IS. It is therefore important to assign genes within the TS critical interval to each of these disorders. Here, we focus on one gene within this interval, PPP2R3B, which encodes a protein phosphatase 2A regulatory subunit that interacts with the origin of replication component, CDC6, and has been linked to regulation of autophagy. We found that PPP2R3B is expressed at sites of chondrogenesis within human foetuses, including the vertebrae. We also demonstrated prominent expression in myotome and muscle fibres in human foetuses, and zebrafish embryos and adolescents. As there is no rodent orthologue of PPP2R3B, we used CRIPSR/Cas9-mediated gene-editing to generate a frameshift mutation in zebrafish ppp2r3b. Adolescent zebrafish that were homozygous for this mutation exhibited a fully penetrant kyphoscoliosis phenotype which became progressively worse over time, mirroring IS in humans. These defects were associated with reduced mineralisation of vertebrae, resembling osteoporosis. Electron microscopy demonstrated abnormal mitochondria adjacent to muscle fibres, a feature which is associated with muscular dystrophy. Collectively, our data support a role for PPP2R3B haploinsufficiency in human IS pathogenesis in TS, establish a new animal model of this condition and provide a basis to investigate the underlying mechanisms. Author Summary Abnormal curvature of the spine is extremely common, often developing as people age. The causes of this are not well understood and a major focus of active research is to identify the underlying genetic causes of this. In this study, we used gene-editing to create zebrafish carrying a mutation in the gene PPP2R3B. This is a gene linked to Turner syndrome in which patients develop spinal curvature, however, it has never been implicated in skeletal tissue maintenance before. Adolescent mutant zebrafish developed spinal curvature which became progressively worse, mirroring the human condition. This was associated with reduced formation of mineralised bone including an osteoporosis-like presentation within vertebrae. This was associated with prominent ppp2r3b expression in axial muscle and a muscular dystrophy-like phenotype. This work provides an experimental starting point to investigate the molecular and cellular mechanisms underlying spinal tissue integrity in future.

BACKGROUND: Long-term outcomes after direct current cardioversion (DCCV) in patients that receive anticoagulation have demonstrated to have no adverse sequela. Less is known about the impact on atrial fibrillation (AF) outcomes and resource utilization of repeated DCCVs that are often required for long-term rhythm control. METHODS: A total of 4,135 AF patients >18 years of age that underwent DCCV with long-term system follow-up were evaluated. Patients were stratified by the number of DCCVs received: 1 (n=2,201), 2-4 (n=1,748), and ≥5 (n=186). Multivariable Cox hazard regression was used to determine the association of DCCV categories to the outcomes of death, AF hospitalization, AF ablation, DCCVs, and stroke/transient ischemic attack. RESULTS: The average follow-up of the patient population was 1,633.1±1,232.9 (median: 1,438.0) days. Patients who underwent 2-4 and ≥5 DCCVs had more comorbidities, namely hypertension, hyperlipidemia and heart failure. Anticoagulation use was common at the time of DCCV in all groups (89.1%, 91.2%, 91.9%, p=0.06) and amiodarone use increased with increasing DCCV category (30.1%, 43.4%, 52.2, p5 vs. 1, (HR=1.32 [0.89-1.94], p=0.17). CONCLUSIONS: This study found that the increasing number of DCCVs, despite escalation of other pharmacologic and nonpharmacologic therapies, is a long-term independent risk factor for repeat DCCVs, ablations, and AF hospitalizations among AF patients.

The use of social media expands the availability and sources of career information. However, the authorship of this information has changed from traditional print media and multimedia sources created by experts to social media–based career information created by the users themselves. Although variability in career information validity has been an issue for some time, rapid growth in the use of social media creates some unique challenges. The ease with which social media–based career information can spread creates the potential for rapid widespread dissemination of disinformation and biased perceptions. Potential sources of invalidity include intentional bias (with or without profit motive), unintentional bias, restricted range of experience, out‐of‐date information, popularity bias, similarity bias, and context deficiency. The authors examine potential sources of social media–based career information invalidity and suggest implications for practice to help individuals make the best use of such information. peerReviewed

Magnetic resonance imaging (MRI) in patients with left ventricular (LV) leads may cause tissue or lead heating, dislodgment, venous damage, or lead dysfunction.The purpose of this study was to determine the safety of MRI in patients with LV pacing leads.Prospective data on patients with coronary sinus LV leads undergoing clinically indicated MRI at 3 institutions were collected. Patients were not pacemaker-dependent. Scans were performed under pacing nurse, technician, radiologist, and physicist supervision using continuous vital sign, pulse oximetry, and ECG monitoring and a 1.5-T scanner with specific absorption rate1.5 W/kg. Devices were interrogated pre- and post-MRI, programmed to asynchronous or inhibition mode with tachyarrhythmia therapies off (if present), and reprogrammed to their original settings post-MRI.MRI scans (n = 42) were performed in 40 patients with non-MRI conditional LV leads between 2005 and 2013 (mean age 67 ± 9 years, n = 16 [40%] women, median lead implant duration 740 days with interquartile range 125-1173 days). MRIs were performed on the head/neck/spine (n = 35 [83%]), lower extremities (n = 4 [10%]), chest (n = 2 [5%]), and abdomen (n = 1 [2%]). There were no overall differences in pre- and post-MRI interrogation LV lead sensing (12.4 ± 6.2 mV vs 12.9 ± 6.7 mV, P = .38), impedance (724 ± 294 Ω vs 718 ± 312 Ω, P = .67), or threshold (1.4 ± 1.1 V vs 1.4 ± 1.0 V, P = .91). No individual LV lead changes required intervention.MRI scanning was performed safely in non-pacemaker-dependent patients with coronary sinus LV leads who were carefully monitored during imaging without clinically significant adverse effect on LV lead function.

This annual review of the career counseling and development literature presents a content analysis of refereed journal articles published in 2013. Four research questions guided the analysis: (a) What content topics were included in career development articles published in refereed journals in 2013? (b) To what extent are theory, research, and practice integrated in career development articles published in refereed journals in 2013? (c) What variation exists in the characteristics of career development articles published in refereed journals in 2013? and (d) What variation exists in the content included in theory, research, and practice articles? A total of 360 unique topics were identified in 357 articles from 24 journals. Results indicated that topic content in journals evolved slowly with limited integration of theory, research, and practice. Implications are suggested for (a) future topic content; (b) better integration of theory, research, and practice; (c) education and training; (d) journal editorial policy; and (e) future content analyses of journal articles.Keywords: content analysis, career development literature, theory, research, practiceThe Career Development Quarterly (CDQ) has published an annual review of the career counseling and development literature each year since 1989. The number of articles and journals represented in the reviews has grown over time. Each one of those 25 reviews provided a brief summary of the content of articles by topic, as well as a commentary on the nature of the literature published that year (Arbona, 2000; Bikos, Dykhouse, Boutin, Gowen, & Rodney, 2013; Chope, 2008; Cook, 1991; Creager, 2011; Dagley & Salter, 2004; Erford & Crockett, 2012; Flores et ah, 2003; Guindon & Richmond, 2005; Harrington & Harrigan, 2006; Hartung, 2010; Jepsen, 1992; Luzzo & MacGregor, 2001; Niles, 1997; Patton & McIlveen, 2009; Salomone, 1993; Savickas, 1989; Spokane & Hawks, 1990; Stoltz-Loike, 1996; Subich, 1994; Swanson & Parcover, 1998; Tien, 2007; Walsh & Srsic, 1995; Whiston & Brecheisen, 2002; Young & Chen, 1999). In reviewing past CDQ annual reviews, we identified some noteworthy trends. The first trend is that the previous CDQ annual reviews tended to include articles from common journals, including CDQ, Journal of Vocational Behavior (JVB), Journal of Career Assessment (JCA), and Journal of Employment Counseling (JEC). The second trend involved the method for summarizing the literature. Most authors used headings to identify clusters of content in the literature. Finally, some reviews explicitly posed a focus question reflecting the practical purpose of the annual review, such as "How can the research published last year be useful to counselors?" (Erford & Crockett, 2012, p. 291); "What can the reader learn about career counseling and development from these articles?" (Savickas, 1989, p. 127); and "What can the practitioner and researcher learn from the literature to aid their work?" (Jepsen, 1992, p. 99). Our 2013 review builds on previous reviews while also using a content analysis approach to examine the literature. We also include a special emphasis on analyzing the literature in terms of integrating theory, research, and practice.Content Analyses of Journal ArticlesContent analyses of journal articles provide an opportunity for a discipline to periodically evaluate the congruence of the professional literature with the discipline's purpose, interests, and values (Buboltz, Deemer, & Hoffman, 2010; Lee, Rosen, & Bums, 2013). Journal article content analyses also identify trends and changes, which likely affect counseling practice (Loveland, Buboltz, Schwartz, & Gibson, 2006; Williams & Buboltz, 1999). These are the aims of the current review.Content analyses of journal articles take four basic forms. The first involves analyzing the content of multiple journals in career development in a given year, such as those published in CDQ, beginning with Savickas's 1988 review (Savickas, 1989) and continuing through Bikos et al. …

WDR11 has been implicated in congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility. However, WDR11’s role in development is poorly understood. Here we report that WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for ciliogenesis. Disruption of WDR11 expression in mouse and zebrafish results in phenotypic characteristics associated with defective Hh signalling, accompanied by dysgenesis of ciliated tissues.Wdr11null mice also exhibit early onset obesity. We found that WDR11 shuttles from the cilium to the nucleus in response to Hh signalling. WDR11 was also observed to regulate the proteolytic processing of GLI3 and cooperate with EMX1 transcription factor to induce the expression of downstream Hh pathway genes and gonadotrophin releasing hormone production. The CHH/KS-associated human mutations result in loss-of-function of WDR11. Treatment with the Hh agonist purmorphamine partially rescued the WDR11-haploinsufficiency phenotypes. Our study reveals a novel class of ciliopathy caused by WDR11 mutations and suggests that CHH/KS may be a part of the human ciliopathy spectrum.

We describe a mutation inLMOD1, which predisposes individuals to thoracic aortic aneurysms and dissections in a large multi-generation British family. Exome variant profiles for the proband and two distantly related affected relatives were generated and a rare protein-altering, heterozygous variant was identified, present in all the exome-sequenced affected individuals. The allele c.1784T>C, p.(V595A) inLMOD1is located in a known actin-binding WH2 domain and is carried by all living affected individuals in the family.LMOD1was further assessed in a consecutive series of 98 UK TAAD patients and one further mutation was found, yielding an incidence of ∼2% in our study group. Assessment ofLMOD1in international TAAD cohorts discovered nine other missense variants of which three were classed as likely pathogenic.Validation ofLMOD1was undertaken using a zebrafish animal model. Knock-down of bothlmod1aandlmod1bparalogs using morpholino oligonucleotides showed a reproducible abnormal phenotype involving the aortic arches under off-target controls. Injection of the humanLMOD1c.1784T>C, p.(V595A) mutation demonstrated a likely dominant negative effect and illustrated a loss of function cause.Mutations found in the WH2 actin-binding domain ofLMOD1may delay actin polymerization and therefore compromise actin length, dynamics and interaction with myosin in the smooth muscle contraction pathway.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjogren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability.

Background The mechanisms behind the association of atrial fibrillation ( AF ) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long‐term anticoagulation exposure. Methods and Results A total of 10 537 patients anticoagulated with warfarin (target INR 2–3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF . The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P P P AF patients compared with matched non‐ AF patients (total dementia: hazard ratio [HR]=2.42 [1.85–3.18], P HR =2.04 [1.40–2.98], P HR =2.46 [1.58–3.86], P AF (26–50% versus >75%: HR =2.51, P =0.005) and non‐ AF groups (≤25% versus >75%: HR =3.92, P Conclusions The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients.

Understanding the role of basal bodies (BBs) during development and disease has been largely overshadowed by research into the function of the cilium. Although these two organelles are closely associated, they have specific roles to complete for successful cellular development. Appropriate development and function of the BB are fundamental for cilia function. Indeed, there are a growing number of human genetic diseases affecting ciliary development, known collectively as the ciliopathies. Accumulating evidence suggests that BBs establish cell polarity, direct ciliogenesis, and provide docking sites for proteins required within the ciliary axoneme. Major contributions to our knowledge of BB structure and function have been provided by studies in flagellated or ciliated unicellular eukaryotic organisms, specifically Tetrahymena and Chlamydomonas. Reproducing these and other findings in vertebrates has required animal in vivo models. Zebrafish have fast become one of the primary organisms of choice for modeling vertebrate functional genetics. Rapid ex-utero development, proficient egg laying, ease of genetic manipulation, and affordability make zebrafish an attractive vertebrate research tool. Furthermore, zebrafish share over 80 % of disease causing genes with humans. In this article, we discuss the merits of using zebrafish to study BB functional genetics, review current knowledge of zebrafish BB ultrastructure and mechanisms of function, and consider the outlook for future zebrafish-based BB studies.

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that is generally inherited in an autosomal recessive fashion. However, in some families, trans mutant alleles interact with the primary causal locus to modulate the penetrance and/or the expressivity of the phenotype. CCDC28B (MGC1203) was identified as a second site modifier of BBS encoding a protein of unknown function. Here we report the first functional characterization of this protein and show it affects ciliogenesis both in cultured cells and in vivo in zebrafish. Consistent with this biological role, our in silico analysis shows that the presence of CCDC28B homologous sequences is restricted to ciliated metazoa. Depletion of Ccdc28b in zebrafish results in defective ciliogenesis and consequently causes a number of phenotypes that are characteristic of BBS and other ciliopathy mutants including hydrocephalus, left-right axis determination defects and renal function impairment. Thus, this work reports CCDC28B as a novel protein involved in the process of ciliogenesis whilst providing functional insight into the cellular basis of its modifier effect in BBS patients.

The popularity and growth of social networking sites (SNSs), particularly among the college-aged demographic, makes them logical tools for university career centers to use to connect with students. The authors surveyed 78 university career centers to determine how they use SNSs, the benefits and drawbacks, and the advice they would give to a career center considering using SNSs. The most commonly used SNSs by this sample include Facebook, LinkedIn, and Twitter, mainly to provide career information. Benefits included students' responsivity to the SNS posts and increased visibility and attendance at events; the main drawback was time required. The most common recommendation was to determine goals and plan implementation. Keywords: social networking sites, Facebook, Twitter, Linkedln, university career centers Social networking ntes (SNSs) have been defined as "Web-based services that allow individuals to ( 1 ) construct a public or semi-public profile within a bounded system, (2) articulate a list of other users with whom they share a connection, and (3) view and traverse their list of connections and those made by others within the system" (Boyd & Ellison, 2007, p. 2 1 1 ). Jencius and Rainey (2009) identified Facebook, Linkedln, and Twitter as examples of SNSs that are becoming increasingly popular, each having millions of users, seen as "tremendous vehicles for connecting with others, be it socially or professionally" (p. 22). Facebook is the most frequently used SNS, with over 901 million monthly users, 526 million daily active users, and more than 125 billion friend connections (Facebook Statistics, 2012). Facebook's purpose is to "give people the power to share and make the world more open and connected" (About Facebook, 2012). Individuals provide information on a profile page and can upload links, photos, videos, notes, or brief status updates and connect with others when invited to "friend" another Facebook user or by personally initiating the invitation. Facebook includes job search applications, or apps, including LinkUp (companies can post job openings on Fan Pages), virtual business cards, Inside Job, My linkedln Profile (connecting with a Linkedln account), and Work With Us (by Jobvite). Twitter is a microbloggjng tool, through which a person may "tweet" about their lives in 140 characters or less. Twitter, unlike Facebook and linkedln, allows for asymmetric relations, that is, a person can follow another without that person having to follow in return. Twitter is "the fastest, simplest way to stay close to everything you care about" (About Twitter, 2012). Although Twitter does not provide statistics, according to a blog on msnbc, Twitter now has over 140 million active users who generate over 400 million tweets per day (@technolog, 2012). According to Jencius and Rainey (2009), Linkedln differs from Facebook and Twitter because it is used for more professional purposes, similar to a business card exchange. Linkedln lists over 161 million members and more than 2 million companies, with all Fortune 500 companies represented (About Us, 2012). They provide a "gated access" to members, in which contacts must know each other or be introduced to each other from a common contact. Members can write endorsements of other contacts, which serve as brief letters of recommendation and can be seen by employers. According to their website, Linkedln will help members (a) reconnect: "find past and present colleagues and dassmates quickly," (b) power your career: "discover inside connections when you are looking for a job or new business opportunity," and (c) get answers: "your network is lull of industry experts willing to share advice" (Get The Most, 2012). College students regularly use SNSs. In a study of 7,705 college students, Junco and Mastrodicasa (2007) reported the following characteristics of those students: 97% owned a computer, and 68% had a Facebook account and logged in at [cast twice per day. …

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.