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Objective To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). Participants Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. Evidence The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. Consensus process In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as "expert opinion." Conclusions Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD.

Colorectal cancer (CRC) is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, noncoding RNA molecules that have a major role in gene expression regulation and are dysregulated in CRC. The miR-200 family is involved in epithelial-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in CRC. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017. Both in vitro and human studies reporting on the miR-200 family and CRC were included. Studies describing molecular pathways and the role of the miR-200 family in the diagnostic and therapeutic management of CRC were analyzed. Thirty-four studies (22 in vitro and 18 human studies) were included. miR-200 family expression is regulated epigenetically and via transcriptional factor regulation. In vitro studies show that transfection of miR-200 family members into chemo-resistant colon cancer cell lines results in improved chemo-sensitivity and epithelial phenotype restoration. There is intra-tumoral variability in the tissue expression of miR-200 family members with decreased expression at the invasive front. Clinical studies in CRC patients have shown decreased primary tumor tissue expression of miR-429, miR-200a and miR-200c may be associated with worse survival. Conversely, increased blood levels of miR-141, miR-200a and miR-200c may be associated with worse outcomes. The miR-200 family has a central role in EMT. The miR200 family has potential for both prognostic and therapeutic management of CRC.

Harbour seals (Phoca vitulina) occur in the Arctic but little is known of their population abundance and natural history. In western Hudson Bay, they occur at lower numbers relative to ringed seals (Pusa hispida) and their distribution is largely unknown. However, a reduction in the duration of periods of ice cover in Hudson Bay may be shifting the habitat suitability of the region towards one that favours harbour seals. Harbour seal counts from a known haul-out site at the upstream extent of the Churchill River estuary, located in northern Manitoba, were examined in relation to sea ice conditions in western Hudson Bay. The Churchill River estuary haul-out site was observed directly or remotely (via GigaPan™ photos) during the open-water seasons in 1996, 1999, 2000, and 2005, and from 2014 to 2016. We documented an increase in abundance over the study period; the maximum number of harbour seals observed hauled out at one time was 142 in 2016, compared to a maximum of 32 observed during monitoring activities conducted between 1996 and 2005. In addition, newly born harbour seal pups were observed at the haul-out site during the latter study years, an occurrence not observed from 1996 to 2005. We suggest that an increase in the abundance of harbour seals in Hudson Bay and potentially the entire Arctic may be observed if climate change related reductions in the duration of ice cover continue.

The Erin modern marginal-marine depositional system sits along the Trinidad southwestern coastline. It is among the many unstudied and undocumented modern, dynamic coastal depositional systems around Trinidad. Our study defines the Erin system as being a deflected and asymmetric wave-dominated delta, and in so doing, elucidates the dynamics of the Erin system. This was done using a compendium of satellite images, temporal cross-shore elevation profiles, modern shallow sediment cores, and sediment samples. Geomorphologically, the Erin system comprises a vegetated delta plain and the unvegetated modern deposits. The delta plain has four amalgamated sand bars with intercalated lagoonal deposits. The unvegetated modern deposits is defined as the fifth bar of the system. These five bars were loosely correlated to the five 6th order eustatic cycles of the Holocene highstand. The modern, unvegetated deposit of the fifth bar is divided into an updrift segment and a downdrift segment relative to the inlet mouth. The updrift segment comprises a spit and beach depositional elements, while the downdrift segment comprises a barrier spit, back-barrier lagoon, rip-channels, and sometimes a bayhead delta at the Erin River mouth. The dynamic, annual evolution of the spit reflects a seasonally controlled, possibly cyclical evolution wherein the delta transitions from being asymmetric to deflected-asymmetric. This phenomenon is postulated to be brought on by seasonal changes in the wave regime, and not, as one might expect, seasonally controlled river discharge. That is, during the summer wave season, when net-deposition occurs, the system morphology is deflected as a consequence of increase sedimentation in the nearshore. During the winter wave season, when net-erosion is expected, the system morphology reflects that of a typical asymmetric delta, as a consequence of reduced sedimentation in the nearshore. This cyclical movement of sediment is also observed in cross-shore elevation profiles. Sedimentologically, six depositional elements were sampled using sediment cores: foreshore, updrift spit, channel bars, mouth bar, barrier spit (downdrift), and back-barrier lagoon. Physical sedimentary structures reflected wave energy dominance across the system with an increase in tidal signatures within the lagoon deposits and lower foreshores. Biogenic sedimentary structures were limited across much of the system, but the traces recorded were mostly isolated in the downdrift back-barrier lagoon deposits, and few in the upper barrier spit. Grainsize distributions showed an average grainsize of fine sand across the system with coarse-grained, poorly sorted, bio-clastic sands present as channel lag deposits. An increase in mud content was recorded in the downdrift segment of the delta. The geomorphological, sedimentological, and ichnological data described above provided sufficient evidence to define the Erin system as an asymmetric wave-dominated delta with seasonally controlled deflected morphology.

In view of the learning divide between the children in ordinary families and those in foster homes, online one-to-one tutoring has been provided by university students as a service-learning option. Through the synchronous e-tutoring system platform, the goal of this study is to develop a service learning mode for creating campus-community partnerships and mutual learning experiences. Thus the study applies Ramsden’s theory of university teaching (2003) into an action research project for investigating (i) how e-tutoring can solve the problems occurring in face-to-face tutoring in foster homes; (ii) the effects of e-tutoring; (iii) the new issues identified; and (iv) new strategies for future iterations of the program. For explaining a social phenomenon through a theoretical framework, grounded theory analysis was applied and eight themes were identified in the qualitative data of 10 observation reports, 28 interviews, and 140 weekly journals from both ends of two foster homes and one university. Eight subcategories (content and learning, practical learning, tutoring concerns, knowledge gains, competency gains, adult guidance, e-tutoring approaches, and transformative development) are categorized along with Ramsden’s hierarchy theory—teaching as telling or transmission, teaching as organizing student activity, and teaching as making learning possible. With transformative development of the campus-community partnership the consensus goal among university faculty, directors of foster homes and relevant personnel of e-tutoring (Enos and Morton 2003), the study discussed future improvements for the e-tutoring program. The action research strongly suggests that e-tutoring should emphasize more reflective listening rather than subject-mattered achievement and turn service-learning into an opportunity of achieving the sustainable integration of community resources and social welfare institutions.

The age, palaeoenvironment and formation placement of the conglomeratic Los Atajos Member of central Trinidad have long been unclear. Seven samples (four from calcareous silts near the member's base exposed by building work at the Los Atajos Community Centre, and three from the underlying calcareous claystones of the Brasso Formation) were examined for calcareous microfossils. These indicate a conformable succession encompassing an overall regression. The oldest of the claystone samples, of uppermost early Middle Miocene Globorotalia fohsi fohsi Zone age (N11), contained an upper bathyal benthic foraminiferal assemblage, while the younger claystone samples yielded abundant, shallow neritic Hanzawaia carstensi. The recovery of the planktonic foraminifera Globorotalia mayeri but absence of Globigerinoides subquadratus suggest a Middle Miocene age (Globorotalia mayeri planktonic foraminiferal Zone; N14) for both the uppermost Brasso claystone sample and the Los Atajos Member. The benthic foraminiferal fauna in the Los Atajos is dominated by Rosalina subaraucana, with subdominant Cibicides ex gr. aknerianus and C. floridanus sensu Galloway and Heminway, and common Elphidium spp. This faunal succession has a close affinity with that of parts of the Lower to Middle Miocene Brasso Formation, especially the N10 Guaracara Limestone Member and the clays on which it sits. However, the Los Atajos Member assemblage differs markedly from that of the overlying Late Miocene San Jose Calcareous Silt Member of the Manzanilla Formation, from which the Los Atajos is separated by an unconformity of Globorotalia menardii (N15) Zone age. On these grounds, the Los Atajos Member is here placed within the Brasso Formation. The low diversity, high dominance benthic foraminiferal fauna and the associated ostracod assemblage in the Los Atajos are indicative of inner to shallower middle neritic palaeodepths in a carbonate-prone palaeoenvironment with marine vegetation and strong current action. It is concluded that the Los Atajos was deposited prior to the Late Miocene diversion of the palaeo-Orinoco River towards Trinidad, which is marked by the Manzanilla Formation.

As quality improvement and patient safety come to play a larger role in health care, academic medical centers and health systems are poised to take a leadership role in addressing these issues. Academic medical centers can leverage their large integrated footprint and have the ability to innovate in this field. However, a robust quality management infrastructure is needed to support these efforts. In this context, quality and safety are often described at the executive level and at the unit level. Yet, the role of individual departments, which are often the dominant functional unit within a hospital, in realizing health system quality and safety goals has not been addressed. Developing a departmental quality management infrastructure is challenging because departments are diverse in composition, size, resources, and needs.In this article, the authors describe the model of departmental quality management infrastructure that has been implemented at the Johns Hopkins Hospital. This model leverages the fractal approach, linking departments horizontally to support peer and organizational learning and connecting departments vertically to support accountability to the hospital, health system, and board of trustees. This model also provides both structure and flexibility to meet individual departmental needs, recognizing that independence and interdependence are needed for large academic medical centers. The authors describe the structure, function, and support system for this model as well as the practical and essential steps for its implementation. They also provide examples of its early success.

Background: Arthroscopic criteria for identifying syndesmotic disruption have been variable and subjective. We aimed to quantify syndesmotic disruption arthroscopically using a standardized measurement device. Methods: Ten cadaveric lower extremity specimens were tested in intact state and after serial sectioning of the syndesmotic structures (anterior inferior tibiofibular ligament [AiTFL], interosseous ligament [IOL], posterior inferior tibiofibular ligament [PiTFL], deltoid). Diagnostic ankle arthroscopy was performed after each sectioning. Manual external rotational stress was applied across the tibiofibular joint. Custom-manufactured spherical balls of increasing diameter mounted on the end of an arthroscopic probe were inserted into the tibiofibular space to determine the degree of diastasis of the tibiofibular joint under each condition. Results: A ball 3 mm in diameter reliably indicated a high likelihood of combined disruption of the AiTFL and IOL. Disruption of the AiTFL alone could not be reliably distinguished from the intact state. Conclusion: Use of a spherical probe placed into the tibiofibular space during manual external rotation of the ankle provided an objective measure of syndesmotic instability. Passage of a 2.5-mm probe indicated some disruption of the syndesmosis, but the test had poor negative predictive value. Passage of a 3.0-mm spherical probe indicated very high likelihood of disruption of both the AiTFL and the IOL. Clinical Relevance: The findings challenge the previously used but unsupported standard of a 2-mm diastasis of the tibiofibular articulation for diagnosis of subtle syndesmotic instability.

We investigated talus and tibial plafond subchondral bone puncture strength based on surface location. Puncture tests of the subchondral bone were performed in 9 equal zones on the articular surface of 12 cadaver specimens aged 49.1 years (range, 36-56 years). Compressive load was applied through a microfracture awl at 2 mm/min. Puncture strength was defined as the first load drop in load-deflection curves. In the talus, zone 1 (215 ± 91 N) and zone 2, the anterior medial and anterior middle zones, had significantly greater puncture strength than zones 7, 8, and 9, the posterior medial, middle, and lateral zones (104 ± 43 N, 115 ± 43 N, and 102 ± 35 N, respectively; P < .001). In the tibial plafond, zone 3, the anterior-lateral zone, and zone 7, the posterior medial zone, had significantly greater strength than zone 8, the posterior middle zone (202 ± 72 N, 206 ± 121 N, and 112 ± 65 N, respectively; P < .001) These results suggest that the subchondral bone is significantly weaker to penetrative force in the posterior region than in the anterior region of the talar dome and of the tibial plafond. These findings may have implications for microfracture awl design and for understanding the complex anatomy and physiology of the ankle joint. Levels of Evidence: Controlled laboratory study

The aim of this article is to compare diameter and stiffness, displacement, and strain in a five-strand versus four-strand hamstring graft for anterior cruciate ligament reconstruction. Eight matched pairs of lower extremities underwent four-strand or five-strand hamstring graft reconstruction. Diameter was significantly higher in the five-strand versus the four-strand construct (p = 0.002). No significant difference was found between the groups in construct displacement or stiffness. Significantly higher strain was observed in the inner limb versus the outer limb in the four-strand construct (p = 0.001) and in the inner limb versus the fifth limb in the 5-strand construct (p = 0.004). A fifth limb added to a four-strand hamstring graft significantly increased graft diameter but did not significantly change stiffness or displacement, suggesting that attachment of additional graft material via suture did not provide for full incorporation of the added limb into the graft at time zero. The inner limb in both constructs absorbed significantly greater load than did other limbs. The use of suture to attach additional material to a four-strand hamstring graft may not contribute to improved biomechanical qualities of the graft at time zero.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Heart attacks and myocardial ischemia can be diagnosed by electrocardiogram (EKG). Some of the changes are typical, others are more subtle, and none of the changes are completely sensitive or specific. Additionally, myocardial infarctions demonstrate typical changes over time, or “evolve” in characteristic ways.

Low voltage is a fairly common finding on EKGs, with a limited list of causes. Hypothermia’s characteristic EKG finding is the Osborn wave, which resolves with rewarming. Hyperkalemia can cause tall (>10 mm) T waves, wide QRS, or ventricular tachycardia.

Through collaboration with Inuit hunters, we examined the stomach contents of 142 seals (ringed seals [Phoca hispida; n = 135], bearded seals [Erignathus barbatus; n = 6], and one harbour seal [Phoca vitualina; n = 1]) hunted between 2007 and 2019 from communities around Nunavut to assess whether seals in the eastern Canadian Arctic ingest and retain plastics in their stomachs. The seals in this study ranged from juveniles to adults of up to 30 years of age, and 55% of the seals were males. We found no evidence of plastic ingestion in any of the seals suggesting that seals in Nunavut are not accumulating plastics (>425 μm) in their stomachs. These data provide important baseline information for future plastic pollution monitoring programs in the Arctic.

The rate of postoperative morbidity and mortality after subdural hematoma (SDH) evacuation is high. The aim of this study was to compare mortality statistics from a high-volume database to historical figures and determine the most significant preoperative predictors of mortality and length of stay (LOS). The National Surgical Quality Improvement Program registry was searched (2005-2016) for patients with operatively treated SDHs, of which 2709 were identified for univariate analysis. After exclusion for missing data, 2010 individuals were analyzed with multivariable logistic regression. Primary outcome was 30-day mortality. The average patient age was 68.8 ± 14.9 years, and 64.1% were males. Upon multivariate analysis, nine variables were found to be associated with increased mortality: platelet count < 135,000 (OR 2.04, 95% CI 1.39-2.99), INR >1.2 (OR 1.87, 95% CI 1.34-2.6), bleeding disorder (OR 1.80, 95% CI 1.32-2.46), need for dialysis within two weeks preoperatively (OR 5.69, 95% CI 3.15-10.27), ventilator dependence in the 48 hours preceding surgery (OR 3.99, 95% CI 2.82-5.63), disseminated cancer (OR 2.95, 95% CI 1.34-6.47), WBC count >10,000 (OR 1.55, 95% CI 1.15-2.08), totally dependent functional status (OR 1.84, 95% CI 1.2-2.8), and each increasing year of age (OR 1.04, 95% CI 1.031-1.05). It is not surprising that chronic conditions and functional status were associated with increased mortality. However, specific laboratory abnormalities were also associated with increased mortality at levels generally considered within normal limits. More studies are needed to determine if correcting lab abnormalities preoperatively can improve outcomes in patients with intrinsic coagulopathy.

This study aimed to determine whether manipulation of the microRNA‑200 (miR‑200) family could influence colon adenocarcinoma cell behavior. The miR‑200 family has a significant role in tumor suppression and functions as an oncogene. In vitro studies on gain and loss of function with small interfering RNA demonstrated that the miR‑200 family could regulate RASSF2 expression. Knockdown of the miR‑200 family in the HT‑29 colon cancer cell line increased KRAS expression but decreased signaling in the MAPK/ERK signaling pathway through reduced ERK phosphorylation. Increased expression of the miR‑200 family in the CCD‑841 colon epithelium cell line increased KRAS expression and led to increased signaling in the MAPK/ERK signaling pathway but increased ERK phosphorylation. Functionally, knockdown of the miR‑200 family led to decreased cell proliferation in the HT‑29 cells; therefore, increased miR‑200 family expression could increase cell proliferation in the CCD‑841 cell line. The present study included a large paired miR array dataset (n=632), in which the miR‑200 family was significantly found to be increased in colon cancer when compared with normal adjacent colon epithelium. In a miR‑seq dataset (n=199), the study found that miR‑200 family expression was increased in localized colon cancer compared with metastatic disease. Decreased expression was associated with poorer overall survival. The miR‑200 family directly targeted RASSF2 and was inversely correlated with RASSF2 expression (n=199, all P

This study sought to determine if traction through the index or long finger metacarpal provided a selective distraction force through either the distal radius' radial or ulnar column. In eight specimens, the radius was cut transversely 1 cm proximal to the Lister tubercle. Index and long finger metacarpals were cut and two-hole plates were fixed to metacarpals. Traction forces were alternately applied to index, then long finger metacarpals, sequentially through each metacarpal from 4.5N to 89N. Traction loading through the index finger metacarpal resulted in significantly more distraction force transmitted through the distal radius fragment's radial column at all force intervals. Traction loading through long finger metacarpal resulted in significantly higher force transmission through distal radius' ulnar column. In both cohorts, force transmission increased linearly in response to higher loads. Selective traction force of either the index or long finger metacarpal resulted in differential tensioning of the distal radius' ulnar and radial columns. (Journal of Surgical Orthopaedic Advances 28(2):104-107, 2019).