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BackgroundElevated intracranial pressure (eICP) is a serious medical emergency that requires prompt identification and monitoring. The current gold standards of eICP detection require patient transportation, radiation, and can be invasive. Ocular ultrasound has emerged as a rapid, non-invasive, bedside tool to measure correlates of eICP. This systematic review seeks to explore the utility of ultrasound detected optic disc elevation (ODE) as an ultrasonographic finding of eICP and to study its sensitivity and specificity as a marker of eICP.MethodsThis systematic review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. We systematically searched PubMed, EMBASE, and Cochrane Central for English articles published before April 2023; yielding 1,919 total citations. After eliminating duplicates, and screening the records, we identified 29 articles that addressed ultrasonographically detected ODE.ResultsThe 29 articles included a total of 1249 adult and pediatric participants. In patients with papilledema, the mean ODE ranged between 0.6 mm and 1.2 mm. Proposed cutoff values for ODE ranged between 0.3 mm and 1 mm. The majority of studies reported a sensitivity between 70 and 90%, and specificity ranged from 69 to 100%, with a majority of studies reporting a specificity of 100%.ConclusionsODE and ultrasonographic characteristics of the optic disc may aid in differentiating papilledema from other conditions. Further research on ODE elevation and its correlation with other ultrasonographic signs is warranted as a means to increase the diagnostic accuracy of ultrasound in the setting of eICP.

IntroductionThe optimal pain management strategy after lung transplantation is unknown. This study compared analgesic outcomes of intercostal nerve blockade by cryoanalgesia (Cryo) versus thoracic epidural analgesia (TEA).MethodsSeventy-two patients who underwent bilateral lung transplantation via clamshell incision at our center from 2016 to 2018 were managed with TEA (N = 43) or Cryo (N = 29). We evaluated analgesic-specific complications, opioid use in oral morphine equivalents (OME), and pain scores (0-10) through postoperative day 7. Adjusted linear regression was used to assess for non-inferiority of Cryo to TEA.ResultsThe overall mean pain scores (Cryo 3.2 vs TEA 3.8, P = 0.21), maximum mean pain scores (Cryo 4.7 vs TEA 5.5, P = 0.16), and the total opioid use (Cryo 484 vs TEA 705 OME, P = 0.12) were similar in both groups, while the utilization of postoperative opioid-sparing analgesia, measured as use of lidocaine patches, was lower in the Cryo group (Cryo 21% vs TEA 84%, P

In the vertebrate eye, Notch ligands, receptors, and ternary complex components determine the destiny of retinal progenitor cells in part by regulating Hes effector gene activity. There are multiple paralogues for nearly every node in this pathway, which results in numerous instances of redundancy and compensation during development. To dissect such complexity at the earliest stages of eye development, we used seven germline or conditional mutant mice and two spatiotemporally distinct Cre drivers. We perturbed the Notch ternary complex and multiple Hes genes to understand if Notch regulates optic stalk/nerve head development; and to test intracellular pathway components for their Notch-dependent versus -independent roles during retinal ganglion cell and cone photoreceptor competence and fate acquisition. We confirmed that disrupting Notch signaling universally blocks progenitor cell growth, but delineated specific pathway components that can act independently, such as sustained Hes1 expression in the optic stalk/nerve head. In retinal progenitor cells, we found that among the genes tested, they do not uniformly suppress retinal ganglion cell or cone differentiation; which is not due differences in developmental timing. We discovered that shifts in the earliest cell fates correlate with expression changes for the early photoreceptor factor Otx2, but not with Atoh7, a factor required for retinal ganglion cell formation. During photoreceptor genesis we also better defined multiple and simultaneous activities for Rbpj and Hes1 and identify redundant activities that occur downstream of Notch. Given its unique roles at the retina-optic stalk boundary and cone photoreceptor genesis, our data suggest Hes1 as a hub where Notch-dependent and -independent inputs converge.

IntroductionAdvanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m2) patients and analyzed risk factors of OIRD.MethodsPatients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate

IntroductionAdvanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m2) patients and analyzed risk factors of OIRD.MethodsPatients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder that is associated with repetitive head impacts. Neuropathologically, it is defined by the presence of perivascular hyperphosphorylated tau aggregates in cortical tissue (McKee et al., 2016, Acta Neuropathologica, 131, 75-86). Although many pathological and assumed clinical correlates of CTE have been well characterized, its effects on cortical dendritic arbors are still unknown. Here, we quantified dendrites and dendritic spines of supragranular pyramidal neurons in tissue from human frontal and occipital lobes, in 11 cases with (Mage = 79 ± 7 years) and 5 cases without (Mage = 76 ± 11 years) CTE. Tissue was stained with a modified rapid Golgi technique. Dendritic systems of 20 neurons per region in each brain (N = 640 neurons) were quantified using computer-assisted morphometry. One key finding was that CTE neurons exhibited increased variability and distributional changes across six of the eight dendritic system measures, presumably due to ongoing degeneration and compensatory reorganization of dendritic systems. However, despite heightened variation among CTE neurons, CTE cases exhibited lower mean values than Control cases in seven of the eight dendritic system measures. These dendritic alterations may represent a new pathological marker of CTE, and further examination of dendritic changes could contribute to both mechanistic and functional understandings of the disease.

BackgroundNo studies have examined how journal clubs (JCs) are implemented in anesthesiology residency training programs. The goal of the study was to close this gap by (1) examining the format, content, and goals of JCs; (2) identifying features associated with higher resident attendance and JC success; and (3) examining program directors' perspectives on JCs.MethodsA 41-question survey was sent to anesthesiology program directors. Answers were analyzed using multivariable logistic regression, multivariable linear regression, and exploratory factor analysis.ResultsOut of 117 surveys sent across the United States, 80 program directors responded (68.4% response rate). Of the 80 programs, 77 (96.3%) programs have a JC, with 93.2% of them existing for more than 2 years. Most JCs (62.5%) neither formally appraised articles before meetings, nor formally evaluated their JC (59.7%). Faculty alone organized 44.4% and moderated 69.9% of the JCs. The role of residents was primarily limited to presenting selected articles with faculty guidance (83.3%). The average resident attendance was 49.7%. A multivariable linear regression analysis identified mandatory resident attendance, faculty turnout of >5 members, and longer intervals between JC meetings as features associated with higher resident attendance. Only 49.3% of JCs were successful as defined a priori by resident attendance >50% and longevity of ≥2 years. Features associated with JC success based on multivariable logistic regression included mandatory resident attendance and complimentary food.ConclusionsThis largest survey of JCs in anesthesiology found that while JCs are widely established, half of them could be improved.

BackgroundEndothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, L-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage.ObjectiveThis study examined the hemodynamic safety and effect profiles of the combined administration of L-arginine and sildenafil using an in-vivo pig model.MethodsHemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of L-arginine, sildenafil, as well as combined L-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models.ResultsThe combination of L-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of L-arginine.ConclusionsThe combined intravenous administration of sildenafil and L-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and L-arginine plasma concentrations. Hyperosmolality was only a minor factor in L-arginine hemodynamic effects.

BackgroundEndothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, L-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage.ObjectiveThis study examined the hemodynamic safety and effect profiles of the combined administration of L-arginine and sildenafil using an in-vivo pig model.MethodsHemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of L-arginine, sildenafil, as well as combined L-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models.ResultsThe combination of L-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of L-arginine.ConclusionsThe combined intravenous administration of sildenafil and L-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and L-arginine plasma concentrations. Hyperosmolality was only a minor factor in L-arginine hemodynamic effects.

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2, EED, and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12, which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2, EED, and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.

Background:Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions. Methods:Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures. Results:A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients. Conclusion:Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied. ClinicalTrialsgov identifier:NCT02656875.

BackgroundPain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions.MethodsAdult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures.ResultsA total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients.ConclusionOliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied.Clinicaltrialsgov identifierNCT02656875.

Primary graft dysfunction (PGD) following lung transplantation is associated with elevated recipient plasma levels of plasminogen activator inhibitor-1 (PAI-1) and the receptor for advanced glycation end products (RAGE). However, the significance of these biomarkers in the donor plasma is uncertain. We hypothesized that elevated donor plasma levels of PAI-1 and RAGE would be associated with recipient PGD. We carried out a prospective unmatched case-control study of double-lung transplant recipients between May 2014 and September 2015. We compared donor plasma levels of PAI-1 and RAGE using rank-sum tests and t tests, in 12 recipients who developed PGD grade 2 or 3 within 72 hours postoperatively with 13 recipients who did not. Recipients who developed PGD had higher donor plasma levels of PAI-1 than recipients who did not (median 2.7 ng/mL vs 1.4; P = .03). Recipients with PGD also had numerically higher donor plasma levels of RAGE than recipients without PGD, although this difference did not achieve statistical significance (median 1061 pg/mL vs 679; P = .12). Systemic inflammatory responses in the donor, as reflected by elevated plasma levels of PAI-1, may contribute to the risk of developing PGD. Rapid biomarker assessment of easily available plasma samples may assist in donor lung selection and risk stratification.

Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis. However, whether astrocytes do in fact impose a spatial pattern on developing vessels remains unclear, and how astrocytes themselves are guided is unknown. Here we explore the cellular mechanisms that ensure complete retinal coverage by astrocytes and blood vessels in mouse. We find that migrating astrocytes associate closely with the axons of retinal ganglion cells (RGCs), their neighbors in the RNFL. Analysis of Robo1; Robo2 mutants, in which RGC axon guidance is disrupted, and Math5 (Atoh7) mutants, which lack RGCs, reveals that RGCs provide directional information to migrating astrocytes that sets them on a centrifugal trajectory. Without this guidance, astrocytes exhibit polarization defects, fail to colonize the peripheral retina, and display abnormal fine-scale spatial patterning. Furthermore, using cell type-specific chemical-genetic tools to selectively ablate astrocytes, we show that the astrocyte template is required for angiogenesis and vessel patterning. Our results are consistent with a model whereby RGC axons guide formation of an astrocytic network that subsequently directs vessel development.

Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis. However, whether astrocytes do in fact impose a spatial pattern on developing vessels remains unclear, and how astrocytes themselves are guided is unknown. Here we explore the cellular mechanisms that ensure complete retinal coverage by astrocytes and blood vessels in mouse. We find that migrating astrocytes associate closely with the axons of retinal ganglion cells (RGCs), their neighbors in the RNFL. Analysis of Robo1; Robo2 mutants, in which RGC axon guidance is disrupted, and Math5 (Atoh7) mutants, which lack RGCs, reveals that RGCs provide directional information to migrating astrocytes that sets them on a centrifugal trajectory. Without this guidance, astrocytes exhibit polarization defects, fail to colonize the peripheral retina, and display abnormal fine-scale spatial patterning. Furthermore, using cell type-specific chemical-genetic tools to selectively ablate astrocytes, we show that the astrocyte template is required for angiogenesis and vessel patterning. Our results are consistent with a model whereby RGC axons guide formation of an astrocytic network that subsequently directs vessel development.

Factors that affect the removal of organic carbon by heterotrophic bacterioplankton can impact the rate and magnitude of organic carbon loss in the ocean through the conversion of a portion of consumed organic carbon to CO2. Through enhanced rates of consumption, surface bacterioplankton communities can also reduce the amount of dissolved organic carbon (DOC) available for export from the surface ocean. The present study investigated the direct effects of elevated pCO2 on bacterioplankton removal of several forms of DOC ranging from glucose to complex phytoplankton exudate and lysate, and naturally occurring DOC. Elevated pCO2 (1000-1500 ppm) enhanced both the rate and magnitude of organic carbon removal by bacterioplankton communities compared to low (pre-industrial and ambient) pCO2 (250 -~400 ppm). The increased removal was largely due to enhanced respiration, rather than enhanced production of bacterioplankton biomass. The results suggest that elevated pCO2 can increase DOC consumption and decrease bacterioplankton growth efficiency, ultimately decreasing the amount of DOC available for vertical export and increasing the production of CO2 in the surface ocean.

Factors that affect the removal of organic carbon by heterotrophic bacterioplankton can impact the rate and magnitude of organic carbon loss in the ocean through the conversion of a portion of consumed organic carbon to CO2. Through enhanced rates of consumption, surface bacterioplankton communities can also reduce the amount of dissolved organic carbon (DOC) available for export from the surface ocean. The present study investigated the direct effects of elevated pCO2 on bacterioplankton removal of several forms of DOC ranging from glucose to complex phytoplankton exudate and lysate, and naturally occurring DOC. Elevated pCO2 (1000-1500 ppm) enhanced both the rate and magnitude of organic carbon removal by bacterioplankton communities compared to low (pre-industrial and ambient) pCO2 (250 -~400 ppm). The increased removal was largely due to enhanced respiration, rather than enhanced production of bacterioplankton biomass. The results suggest that elevated pCO2 can increase DOC consumption and decrease bacterioplankton growth efficiency, ultimately decreasing the amount of DOC available for vertical export and increasing the production of CO2 in the surface ocean.

Discharge against medical advice (DAMA) can have detrimental effects on patient outcomes. Recently, the diagnosis of posttraumatic stress disorder (PTSD) has been linked with DAMA in the mental health setting. However, PTSD as a risk factor for DAMA in surgical patients has not received much consideration, although such patients may be at risk for triggering or amplification of PTSD symptoms perioperatively. We present the first case report series of three surgical patients with PTSD who left the hospital AMA. These cases differ markedly from DAMA in non-PTSD patients. In all three subjects, the stress of feeling misunderstood by clinicians and the distress of public detainment by hospital security in the setting of chronic PTSD led to aggressive and risky behavior. All three subjects represented a risk to themselves and to others at the time of DAMA. Finally, all three subjects were difficult to contact for follow-up or medical care and missed appointments.

Discharge against medical advice (DAMA) can have detrimental effects on patient outcomes. Recently, the diagnosis of posttraumatic stress disorder (PTSD) has been linked with DAMA in the mental health setting. However, PTSD as a risk factor for DAMA in surgical patients has not received much consideration, although such patients may be at risk for triggering or amplification of PTSD symptoms perioperatively. We present the first case report series of three surgical patients with PTSD who left the hospital AMA. These cases differ markedly from DAMA in non-PTSD patients. In all three subjects, the stress of feeling misunderstood by clinicians and the distress of public detainment by hospital security in the setting of chronic PTSD led to aggressive and risky behavior. All three subjects represented a risk to themselves and to others at the time of DAMA. Finally, all three subjects were difficult to contact for follow-up or medical care and missed appointments.

Nutrient dynamics, phytoplankton rate processes, and export were examined in a frontal region between an anticyclone and a pair of cyclones 120 km off the coast in the southern California Current System (sCCS). Low silicic acid: nitrate ratios (Si:N) and high nitrate to iron ratios (N:Fe) characteristic of Fe-limiting conditions in the sCCS were associated with the northern cyclone and with the transition zone between the cyclones and the anticyclone. Phytoplankton growth in low-Si:N, high-N:Fe waters responded strongly to added Fe, confirming growth limitation by Fe of the diatom-dominated phytoplankton community. Low Si:N waters had low biogenic silica content, intermediate productivity, but high export compared to intermediate Si:N waters indicating increased export efficiency under Fe stress. Biogenic silica and particulate organic carbon (POC) export were both high beneath low Si:N waters with biogenic silica export being especially enhanced. This suggests that relatively high POC export from low Si:N waters was supported by silica ballasting from Fe-limited diatoms. Higher POC export efficiency in low Si:N waters may have been further enhanced by lower rates of organic carbon remineralization due to reduced grazing of more heavily armored diatoms growing under Fe stress. The results imply that Fe stress can enhance carbon export, despite lowering productivity, by driving higher export efficiency.

Nutrient dynamics, phytoplankton rate processes, and export were examined in a frontal region between an anticyclone and a pair of cyclones 120 km off the coast in the southern California Current System (sCCS). Low silicic acid: nitrate ratios (Si:N) and high nitrate to iron ratios (N:Fe) characteristic of Fe-limiting conditions in the sCCS were associated with the northern cyclone and with the transition zone between the cyclones and the anticyclone. Phytoplankton growth in low-Si:N, high-N:Fe waters responded strongly to added Fe, confirming growth limitation by Fe of the diatom-dominated phytoplankton community. Low Si:N waters had low biogenic silica content, intermediate productivity, but high export compared to intermediate Si:N waters indicating increased export efficiency under Fe stress. Biogenic silica and particulate organic carbon (POC) export were both high beneath low Si:N waters with biogenic silica export being especially enhanced. This suggests that relatively high POC export from low Si:N waters was supported by silica ballasting from Fe-limited diatoms. Higher POC export efficiency in low Si:N waters may have been further enhanced by lower rates of organic carbon remineralization due to reduced grazing of more heavily armored diatoms growing under Fe stress. The results imply that Fe stress can enhance carbon export, despite lowering productivity, by driving higher export efficiency.

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

In the offshore waters of Southern California, submesoscale processes associated with fronts may stimulate phytoplankton blooms and lead to biomass shifts at multiple trophic levels. Here we report the results of a study on the cycling of biogenic silica (bSiO2) with estimates of the contributions of diatoms to primary and new production in water masses adjacent to (i.e., coastal or oceanic) and within an offshore front in the Southern California Current Ecosystem (CCE). The coastal and oceanic water were sampled in cyclonic and anticyclonic eddies, respectively, with the frontal water being an interaction region between the eddy types. Concentrations of bSiO2 varied by 25-fold across the front, with concentrations in frontal waters 20-25% of those in coastal waters. Rates of biogenic silica production spanned an equally large range, with rates within the frontal region that were half those in the coastal regions. Contributions of diatoms to primary and new production were disproportionately higher than their contribution to autotrophic biomass in all areas, ranging from 5-8%, 19-30%, and 32-43% for both processes in the oceanic, frontal and coastal waters, respectively. Across the frontal area, diatoms could account for

© 2015. American Geophysical Union. All Rights Reserved. In the offshore waters of Southern California, submesoscale processes associated with fronts may stimulate phytoplankton blooms and lead to biomass shifts at multiple trophic levels. Here we report the results of a study on the cycling of biogenic silica (bSiO 2 ) with estimates of the contributions of diatoms to primary and new production in water masses adjacent to (i.e., coastal or oceanic) and within an offshore front in the Southern California Current Ecosystem (CCE). The coastal and oceanic water were sampled in cyclonic and anticyclonic e ddies, respectively, with the frontal water being an interaction region between the eddy types. Concentrations of bSiO 2 varied by 25-fold across the front, with concentrations in frontal waters 20-25% of those in coastal waters. Rates of biogenic silica production spanned an equally large range, with rates within the frontal region that were half those in the coastal regions. Contributions of diatoms to primary and new production were disproportionately higher than their contribution to autotrophic biomass in all areas, ranging from 5-8%, 19-30%, and 32-43% for both processes in the oceanic, frontal and coastal waters, respectively. Across the frontal area, diatoms could account for < 1.0%, 6-8%, and 44-72% of organic matter export in the oceanic, frontal and coastal waters, respectively. The results suggest that the regions of frontal interactions between eddies in the southern CCE can account for variability in diatom biomass, productivity and export over very short spatial scales that is comparable to the variability observed across the Pacific basin.

In the offshore waters of Southern California, submesoscale processes associated with fronts may stimulate phytoplankton blooms and lead to biomass shifts at multiple trophic levels. Here we report the results of a study on the cycling of biogenic silica (bSiO2) with estimates of the contributions of diatoms to primary and new production in water masses adjacent to (i.e., coastal or oceanic) and within an offshore front in the Southern California Current Ecosystem (CCE). The coastal and oceanic water were sampled in cyclonic and anticyclonic eddies, respectively, with the frontal water being an interaction region between the eddy types. Concentrations of bSiO2 varied by 25-fold across the front, with concentrations in frontal waters 20-25% of those in coastal waters. Rates of biogenic silica production spanned an equally large range, with rates within the frontal region that were half those in the coastal regions. Contributions of diatoms to primary and new production were disproportionately higher than their contribution to autotrophic biomass in all areas, ranging from 5-8%, 19-30%, and 32-43% for both processes in the oceanic, frontal and coastal waters, respectively. Across the frontal area, diatoms could account for

Seborrheic blepharitis (SB) is a chronic inflammation of the lid margins which may compromise the eyelid function up to some extent. It results from immunologic factors and is commonly associated with scalp seborrheic dermatitis, facial seborrheic dermatitis, and acne rosacea. A yellowish greasy crust with morning exacerbations associated with stinging and burning are the usual clinical features. The symptoms can be controlled with good lid hygiene.We present a case 9-year-old girl SB in with a 1-year history, treated without the effect of different drugs (antibiotics-oral, topical; steroids). The patient with complete success responded to oral ketoconazole.

Eponyms are used almost daily in the clinical practice of dermatology. And yet, information about the person behind the eponyms is difficult to find. Indeed, who is? What is this person’s nationality? Is this person alive or dead? How can one find the paper in which this person first described the disease? Eponyms are used to describe not only disease, but also clinical signs, surgical procedures, staining techniques, pharmacological formulations, and even pieces of equipment. In this article we present the symptoms starting with (L) and other. The symptoms and their synonyms, and those who have described this symptom or phenomenon.

Chronic exposure to environmental ultraviolet radiation (UVR) plays a key role both in photocarcinogenesis and induction ofaccelerated skin ageing. Sailors commonly experience a significant number of cutaneous problems, related to the exposure toenvironmental factors due to their working conditions. Among these factors, sun exposure is able to determine both acute andchronic skin damage, mostly linked to the effects of the ultraviolet (UV) radiation on epidermal and dermal structures.We report a case of sailor with cutis rhomboidalis nuchae, solar elastosis, actinic keratosis (AK), numerous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the head and trunk.

Objectives: * To produce a highly accurate, affordable power and energy meter and data logger for use in FSAE EVs. * Satisfy the need for FSAE vehicles being able to self-monitor their power and energy metrics. * Enable collegiate level teams and other to collect more data, allowing them to improve upon their designs. * Integrate our device into the UCI electric racecar.  Advisor: Prof. J. Michael McCarthy

The yellowish discoloration of the palms and skin is reported under different terms: xanthodermia, hypercarotenemia, carotenemia, carotenodermia. Yellow discoloration of the skin may be associated with carotenemia, hypothyroidism, diabetes mellitus, hyperlipoproteinemia, liver disease, and renal disease, meaning that carotenemia is not synonym with yellow skin, but rather one of the cause. We presented an 8 year‐old boy with a yellow discoloration of the palms and soles, observed by the mother 3 weeks prior to medical examination. The discoloration was uniformly distributed, rather symmetrically, no nails changes, just a mild xerosis palmaris on the right hypotenar area. In lab investigations only were: hypercholesterolemia. The final diagnosis was xanthodermia in context of hyperlypoproteinemia type II A.

Reactive arthritis (Reiter’s syndrome), classically includes the triad of symptoms - conjunctivitis, urethritis and arthritis in young male patients after the urogenital or gastrointestinal infection. In the literature it has been described as the syndrome where one ‘‘can’t see, can’t pee, and can’t climb a tree”. In this article we describe, from the dermatological point of view, 2 cases. The first one – the patient with rheumatoid arthritis, for many years under the medication with Leflunomide and Sulfasalazine, diagnosed on clinical and laboratory grounds. The second one – the patient with clearly diagnosed Reiter’s disease (the first clinical manifestation was circinate balanitis long time before the onset of classic triad).

Atopic dermatitis (AD) is a chronic relapsing skin disease, often occurring within the first year of life and affecting up to 20% of children, the majority of whom outgrow the disease within few years. The prevalence of AD in the adult population has been estimated to be much lower (2–9%). Malassezia yeasts was described in a seminal publication by Guého et al. in 1996. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown.IgE-mediated sensitization may not yet be evident in infants or young children but it develops with increasing age. As the skin barrier function in AD is weakened, and the skin is deficient in antimicrobial peptides such as defensins, various microbes are able to colonize the skin and cause secondary infections. IgE binding allergens have been identified in M. sympodialis, M. furfur, and, lately, M. globosa. M. globosa is the most common species on human skin.Clinically, Malassezia allergy may be suspected in patients with atopic dermatitis and; head and neck lesions. Malassezia yeasts stimulate keratinocytes to produce a variety of cytokines in a species-dependent manner. We present a case 22-years-old women with atopic dermatitis and with lesions on the neck.

A 67 year-old man was diagnosed 10 years ago with severe plaque psoriasis and was hospitalized for re-evaluation of therapy. He was treated previously with topical corticosteroids, methotrexate, and phototherapy. As part of the assessment protocol for initiation of biological treatment, a tuberculin skin test was done, which was positive without signs of active tuberculosis. Isoniazid therapy was started with marked improvement of psoriatic lesions before biologic treatment could be initiated.

French manicure, a simple and elegant manicure style, caught the public’s attention by the 19th century in French nail salons. Now this style has spread all over the world and is the first choice of 80% of women in the USA and Europe. It consists of a natural, pink, beige, or nude base tipped with pure white at the distal end.Onycholysis is a disease of the nails characterized by separation of the nail plate from the nail bed, with variable causes. We present 2 cases of onycholysis that resemble the beautiful and elegant French manicure.

Tuberculosis still remains a huge global health problem. Control of tuberculosis expansionis very difficult. It requires the long-term use of anti-mycobacterial drugs. The BacilleCalmette-Guérin (BCG) vaccination protects against tuberculosis-related meningitis and disseminatedtuberculosis. Although vaccination with BCG is considered safe, adverse regional(BCG-itis) and disseminated (BCG-osis) diseases preferentially occur in the immunocompromisedhost. The infection with human immunodeficiency virus (HIV) by mother-to-childtransmission leads to impaired cellular immune responses, a situation that poses a greatchallenge regarding the universal use of BCG vaccine. World Health Organization recommendsthat children who are known to be HIV -infected, even if asymptomatic, should nolonger be immunized with BCG. We report a patient with solitary skin lesion from the BCGinjection site.