However, some patients still had abnormal serum aminotransferase levels even if they has achieved undetectable HBV DNA (or complete viral response, CVR) for a long time, the reasons of which hasn’t been studied. This research aimed to define the risk factors correlated with biochemical abnormality after CVR in patients treated with NAs. Methods: selleck products 388 chronically

HBV infected patients ongoing naive NAs therapy, who achieved undetectable serum HBV DNA (<20IU/ml) during Jan. 2006 and Feb. 2014, were retro- and prospectively followed. Patients were divided into two groups: patients with normal ALT (n=298) and with abnormal ALT (n=90) (defined as serum ALT >40U/L in male or >35U/L in female at least twice consecutively with a interval of 1-3 months after achieving undetectable HBV DNA). Multivariate logistic regression analysis was used to

screen the risk factors of ALT abnormality. Results: The median follow-up duration was 42.0 months. The demographic characteristics http://www.selleckchem.com/products/SB-203580.html (gender, age, family history of HBV infection/cirrhosis/ hepatocellular carcinoma (HCC), alcohol abuse history, et al.), baseline data (HBeAg positivity, ALT, AST, HBV DNA level, et al), antiviral agents, rates of viral breakthrough or optimized therapy and progressing to HCC during therapy, were comparable in both groups. The body mass index (BMI) (24.1 ±3.5 vs. 22.5±3.2 kg/m2, t=4.165, P<0.001), rates of preexisting cirrhosis (45.6 %vs. 27.2%, x2=10.826, P=0.001) and HBeAg seroconversion medchemexpress (58.1 %(25/43) vs. 39.2 %(49/125), x2=5.754, P=0.016) in patients with abnormal ALT levels were higher than patients with normal ALT levels. Multivariate logistic regression analysis showed preexisting cirrhosis (OR=2.472,

95 %CI=1.424-4.292, P=0.001), higher BMI (OR=1.170, 95%CI = 1.077-1.271, P<0.001), and HBV DNA levels at year 1 (OR=1.727, 95 %CI=1.017-2.933, P=0.043) rather than baseline HBV DNA levels, antiviral agents or alcohol intake, were independent risk factors for ALT abnormality after achieving undetectable HBV DNA. Conclusion: Patients with preexisting cirrhosis, higher BMI and HBV DNA levels at year 1 were more likely to show abnormal ALT levels even after achieving undetectable HBV DNA during NAs therapy. Disclosures: Yuankai Wu – Grant/Research Support: Bristol-Myers Squibb Company The following people have nothing to disclose: Yusheng Jie, Xiangyong Li, Guoli Lin, Shu-ru Chen, Xin-Hua Li, Hong Shi, Fangji Yang, Min Zhang, Mingxing Huang, Yunlong Ao, Yihua Pang, Yutian Chong Background and aims: Data are limited on tenofovir (TDF) treatment discontinuation after long-term viral suppression in HBeAg-negative patients. This study investigates whether TDF discontinuation in this scenario is associated with a low rate of virologic relapse.

However, some patients still had abnormal serum aminotransferase levels even if they has achieved undetectable HBV DNA (or complete viral response, CVR) for a long time, the reasons of which hasn’t been studied. This research aimed to define the risk factors correlated with biochemical abnormality after CVR in patients treated with NAs. Methods: www.selleckchem.com/products/NVP-AUY922.html 388 chronically

HBV infected patients ongoing naive NAs therapy, who achieved undetectable serum HBV DNA (<20IU/ml) during Jan. 2006 and Feb. 2014, were retro- and prospectively followed. Patients were divided into two groups: patients with normal ALT (n=298) and with abnormal ALT (n=90) (defined as serum ALT >40U/L in male or >35U/L in female at least twice consecutively with a interval of 1-3 months after achieving undetectable HBV DNA). Multivariate logistic regression analysis was used to

screen the risk factors of ALT abnormality. Results: The median follow-up duration was 42.0 months. The demographic characteristics Protein Tyrosine Kinase inhibitor (gender, age, family history of HBV infection/cirrhosis/ hepatocellular carcinoma (HCC), alcohol abuse history, et al.), baseline data (HBeAg positivity, ALT, AST, HBV DNA level, et al), antiviral agents, rates of viral breakthrough or optimized therapy and progressing to HCC during therapy, were comparable in both groups. The body mass index (BMI) (24.1 ±3.5 vs. 22.5±3.2 kg/m2, t=4.165, P<0.001), rates of preexisting cirrhosis (45.6 %vs. 27.2%, x2=10.826, P=0.001) and HBeAg seroconversion 上海皓元医药股份有限公司 (58.1 %(25/43) vs. 39.2 %(49/125), x2=5.754, P=0.016) in patients with abnormal ALT levels were higher than patients with normal ALT levels. Multivariate logistic regression analysis showed preexisting cirrhosis (OR=2.472,

95 %CI=1.424-4.292, P=0.001), higher BMI (OR=1.170, 95%CI = 1.077-1.271, P<0.001), and HBV DNA levels at year 1 (OR=1.727, 95 %CI=1.017-2.933, P=0.043) rather than baseline HBV DNA levels, antiviral agents or alcohol intake, were independent risk factors for ALT abnormality after achieving undetectable HBV DNA. Conclusion: Patients with preexisting cirrhosis, higher BMI and HBV DNA levels at year 1 were more likely to show abnormal ALT levels even after achieving undetectable HBV DNA during NAs therapy. Disclosures: Yuankai Wu – Grant/Research Support: Bristol-Myers Squibb Company The following people have nothing to disclose: Yusheng Jie, Xiangyong Li, Guoli Lin, Shu-ru Chen, Xin-Hua Li, Hong Shi, Fangji Yang, Min Zhang, Mingxing Huang, Yunlong Ao, Yihua Pang, Yutian Chong Background and aims: Data are limited on tenofovir (TDF) treatment discontinuation after long-term viral suppression in HBeAg-negative patients. This study investigates whether TDF discontinuation in this scenario is associated with a low rate of virologic relapse.

Bile acids activate farnesoid X receptor (FXR) and the G-protein-coupled receptor, TGR5, and also several cell-signaling

pathways to regulate bile acid synthesis and lipid metabolism.[1] Pharmacological activation of either FXR or TGR5 receptor has been shown to improve lipid, glucose, and energy homeostasis, glucose tolerance, and insulin sensitivity.[2, 3] Paradoxically, loss of FXR in obese and diabetic mice reduced body weight and improved peripheral insulin PD0325901 sensitivity,[4] and decreasing bile acid pool size with the specific FXR agonist, GW4064, caused increased susceptibility to diet-induced obesity, fatty liver, and hypertriglyceridemia.[5] It is likely that activation of different bile acid signaling in different mouse models might have different effects on hepatic metabolism, diabetes, and obesity. In Cyp7a1 transgenic (Cyp7a1-tg)

mice, both CYP7A1 enzyme activity and bile acid pool size are doubled,[6] biliary cholesterol and bile acid secretion are stimulated, and serum cholesterol is decreased, whereas serum triglyceride levels remain the same.[7] find more These metabolic changes caused by increased CYP7A1 expression result in significantly improved lipid homeostasis and protection against hepatic steatosis, insulin resistance (IR), and obesity.[6] Therefore, further study is necessary to understand the participation of bile acid synthesis in the regulation of metabolic homeostasis, nonalcoholic fatty liver disease (NAFLD), and diabetes. Bile acid metabolism is closely linked to whole-body cholesterol homeostasis; bile acid synthesis and bile-acid–facilitated biliary cholesterol secretion are the only significant pathways for cholesterol elimination from the body. Furthermore, the liver acquires cholesterol through dietary absorption,

receptor-mediated uptake, and MCE de novo synthesis. Intracellular cholesterol/oxysterols play an important role in the regulation of cholesterol synthesis through the transcriptional factor, sterol response element-binding protein 2 (SREBP2).[8] Upon increased intracellular cholesterol levels, SREBP2 precursor (125 kDa) forms a complex with insulin-induced gene (INSIG) and SREBP cleavage-activating protein (SCAP), which is retained in the endoplasmic reticulum (ER) membrane. When cholesterol levels decrease, SCAP escorts SREBP2 precursor to the Golgi, where two steroid-sensitive proteases (S1P and S2P) cleave an N-terminal fragment (68 kDa), subsequently translocating into the nuclei to activate its target genes, including low-density lipoprotein receptor (LDLR) and key genes involved in de novo cholesterol synthesis.[8] microRNAs (miRs) are small noncoding RNAs that, after base pairing with complementary sequences of target messenger RNAs (mRNAs), promote mRNA degradation or inhibit protein synthesis. miR-33a, encoded by intron 16 of the SREBP2 gene, has recently been shown to regulate cellular cholesterol homeostasis,[9] biliary bile acid secretion,[10] and fatty acid oxidation.

We have retrospectively evaluated the predictive markers of peri-operative major haemorrhages in a large single-centre population (n = 2455) of patients with VWF:RCo <50 IU dL−1 and type 1 VWD, possible type Poziotinib 1 and type 2 VWD. Diagnostic criteria for type 1 and possible type1 (VWF:RCo 15–30 IU dL−1 and 31–49 IU dL−1, respectively),

VWF:RCo/VWF:Ag ratio >0.6 and type 2 with VWF:RCo/VWF:Ag <0.6 were used. For each patient, the severity of each symptom was summarized using the BS system ranging from 0 to 3 [38], according to ISTH recommendations [39], and taking into account the most severe episode for each symptom [40]. The BS was considered useful for the identification of a significant bleeding history (≥5 in females and ≥3 in males) for the diagnosis of type 1 VWD. This approach can also be useful in all VWD types [41,42]. Patient characteristics of group A (without surgical bleeding) and

group FDA approved Drug Library cell assay B (with surgical bleeding) are shown in Table 2. Major surgical bleeding appeared in 26% of all type1 patients (32.6% type1 and 24.8% possible type1) and 54.9% of type 2. Considering surgeries, major haemorrhage was observed in 17.8% of all type1 and 50% of type 2 (Table 3). No significant differences were observed in family history, blood group, age, gender, BS, the number of bleeding sites (Table 1) and laboratory parameters (Table 4), between groups A and B. FVIII levels were not useful as predictors of postoperative bleeding. In possible type 1, group B, a higher frequency of bleeding after medchemexpress tooth extraction (Table 5) and a higher BS in females were found. Postpartum bleeding was the most frequent symptom in type 2 VWD, although not significant. Caesarean section and adeno-tonsillectomy showed the highest frequency of major haemorrhage. Personal bleeding history, especially bleeding after tooth extraction in type 1 VWD [43], and postpartum haemorrhage in type 2 and the type of surgery appear to be predictive markers of major postoperative

haemorrhage. The relative risk (RR) between type 1 and 2 was as expected. Possible type 1 VWD patients showed similar risk of peri-operative major bleeding compared with type 1, again emphasizing the superiority of symptoms over laboratory parameters. Neither the family history nor laboratory parameters could anticipate surgical bleeding. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers.

We have retrospectively evaluated the predictive markers of peri-operative major haemorrhages in a large single-centre population (n = 2455) of patients with VWF:RCo <50 IU dL−1 and type 1 VWD, possible type TSA HDAC supplier 1 and type 2 VWD. Diagnostic criteria for type 1 and possible type1 (VWF:RCo 15–30 IU dL−1 and 31–49 IU dL−1, respectively),

VWF:RCo/VWF:Ag ratio >0.6 and type 2 with VWF:RCo/VWF:Ag <0.6 were used. For each patient, the severity of each symptom was summarized using the BS system ranging from 0 to 3 [38], according to ISTH recommendations [39], and taking into account the most severe episode for each symptom [40]. The BS was considered useful for the identification of a significant bleeding history (≥5 in females and ≥3 in males) for the diagnosis of type 1 VWD. This approach can also be useful in all VWD types [41,42]. Patient characteristics of group A (without surgical bleeding) and

group VX-809 concentration B (with surgical bleeding) are shown in Table 2. Major surgical bleeding appeared in 26% of all type1 patients (32.6% type1 and 24.8% possible type1) and 54.9% of type 2. Considering surgeries, major haemorrhage was observed in 17.8% of all type1 and 50% of type 2 (Table 3). No significant differences were observed in family history, blood group, age, gender, BS, the number of bleeding sites (Table 1) and laboratory parameters (Table 4), between groups A and B. FVIII levels were not useful as predictors of postoperative bleeding. In possible type 1, group B, a higher frequency of bleeding after MCE tooth extraction (Table 5) and a higher BS in females were found. Postpartum bleeding was the most frequent symptom in type 2 VWD, although not significant. Caesarean section and adeno-tonsillectomy showed the highest frequency of major haemorrhage. Personal bleeding history, especially bleeding after tooth extraction in type 1 VWD [43], and postpartum haemorrhage in type 2 and the type of surgery appear to be predictive markers of major postoperative

haemorrhage. The relative risk (RR) between type 1 and 2 was as expected. Possible type 1 VWD patients showed similar risk of peri-operative major bleeding compared with type 1, again emphasizing the superiority of symptoms over laboratory parameters. Neither the family history nor laboratory parameters could anticipate surgical bleeding. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers.

We have retrospectively evaluated the predictive markers of peri-operative major haemorrhages in a large single-centre population (n = 2455) of patients with VWF:RCo <50 IU dL−1 and type 1 VWD, possible type Obeticholic Acid in vivo 1 and type 2 VWD. Diagnostic criteria for type 1 and possible type1 (VWF:RCo 15–30 IU dL−1 and 31–49 IU dL−1, respectively),

VWF:RCo/VWF:Ag ratio >0.6 and type 2 with VWF:RCo/VWF:Ag <0.6 were used. For each patient, the severity of each symptom was summarized using the BS system ranging from 0 to 3 [38], according to ISTH recommendations [39], and taking into account the most severe episode for each symptom [40]. The BS was considered useful for the identification of a significant bleeding history (≥5 in females and ≥3 in males) for the diagnosis of type 1 VWD. This approach can also be useful in all VWD types [41,42]. Patient characteristics of group A (without surgical bleeding) and

group Talazoparib chemical structure B (with surgical bleeding) are shown in Table 2. Major surgical bleeding appeared in 26% of all type1 patients (32.6% type1 and 24.8% possible type1) and 54.9% of type 2. Considering surgeries, major haemorrhage was observed in 17.8% of all type1 and 50% of type 2 (Table 3). No significant differences were observed in family history, blood group, age, gender, BS, the number of bleeding sites (Table 1) and laboratory parameters (Table 4), between groups A and B. FVIII levels were not useful as predictors of postoperative bleeding. In possible type 1, group B, a higher frequency of bleeding after medchemexpress tooth extraction (Table 5) and a higher BS in females were found. Postpartum bleeding was the most frequent symptom in type 2 VWD, although not significant. Caesarean section and adeno-tonsillectomy showed the highest frequency of major haemorrhage. Personal bleeding history, especially bleeding after tooth extraction in type 1 VWD [43], and postpartum haemorrhage in type 2 and the type of surgery appear to be predictive markers of major postoperative

haemorrhage. The relative risk (RR) between type 1 and 2 was as expected. Possible type 1 VWD patients showed similar risk of peri-operative major bleeding compared with type 1, again emphasizing the superiority of symptoms over laboratory parameters. Neither the family history nor laboratory parameters could anticipate surgical bleeding. The authors stated that they had no interests which might be perceived as posing a conflict or bias. “
“Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers.

Although the precise etiological mechanism of DIAIH has not been elucidated yet, we can speculate that the variations in their developing patterns are due to the different metabolic activity and immunological reactions. We think that a wider range of drugs has the potential to cause AIH, and incidence of AIH with a drug-related Silmitasertib cell line etiology is more frequent than we have previously thought. In cases of DILI, careful follow-up will be needed, keeping in mind that AIH can develop even after normalization of

liver enzymes. Furthermore, establishment of the diagnostic criteria and therapeutic strategy for DIAIH will be needed. Kazushi Sugimoto M.D., Ph.D.*, Takeshi Ito M.D., Ph.D.*, Norihiko Yamamoto M.D., Ph.D.*, Katsuya

Shiraki M.D., Ph.D.*, * Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan. “
“Liver fibrogenesis is associated with the transition of quiescent hepatocytes and http://www.selleckchem.com/products/chir-99021-ct99021-hcl.html hepatic stellate cells (HSCs) into the cell cycle. Exit from quiescence is controlled by E-type cyclins (cyclin E1 [CcnE1] and cyclin E2 [CcnE2]). Thus, the aim of the current study was to investigate the contribution of E-type cyclins for liver fibrosis in man and mice. Expression of CcnE1, but not of its homolog, CcnE2, was induced in fibrotic and cirrhotic livers from human patients with different etiologies and in murine wild-type (WT) livers after periodical administration of the profibrotic toxin, CCl4. To further evaluate the potential function of E-type cyclins for liver fibrogenesis, we repetitively treated constitutive 上海皓元 CcnE1−/− and CcnE2−/− knock-out mice with CCl4 to induce liver fibrosis. Interestingly, CcnE1−/− mice were protected against CCl4-mediated liver

fibrogenesis, as evidenced by reduced collagen type I α1 expression and the lack of septum formation. In contrast, CcnE2−/− mice showed accelerated fibrogenesis after CCl4 treatment. We isolated primary HSCs from WT, CcnE1−/−, and CcnE2−/− mice and analyzed their activation, proliferation, and survival in vitro. CcnE1 expression in WT HSCs was maximal when they started to proliferate, but decreased after the cells transdifferentiated into myofibroblasts. CcnE1−/− HSCs showed dramatically impaired survival, cell-cycle arrest, and strongly reduced expression of alpha smooth muscle actin, indicating deficient HSC activation. In contrast, CcnE2-deficient HSCs expressed an elevated level of CcnE1 and showed enhanced cell-cycle activity and proliferation, compared to WT cells. Conclusions: CcnE1 and CcnE2 have antagonistic roles in liver fibrosis. CcnE1 is indispensable for the activation, proliferation, and survival of HSCs and thus promotes the synthesis of extracellular matrix and liver fibrogenesis.

No large-scale genetic studies have been performed thus far in South Asian populations. Therefore, as part of a community-based cohort study in an urban adult population of Sri Lankans, we investigated associations of genetic variants with NAFLD, diagnosed on established ultrasound criteria, and its related phenotypes. Methods: We selected 10 single

nucleotide polymorphisms (SNPs), all previously reported to be associated with NAFLD in populations of European and/or South Asian ancestry, for a case-control replication study. They included loci derived from GWAS [PNPLA3 (rs738409), LYPLAL1 (rs12137855), GCKR (rs780094), PPP1R3B C646 solubility dmso (rs4240624) and NCAN (rs2228603)] plus those from candidate gene studies [APOC3 (rs2854117 and rs2854116), ADIPOR2 (rs767870)

and STAT3 (rs6503695 and rs9891119)]. Genotype data of 2988 participants were used for the 3-deazaneplanocin A nmr analysis. Results: A significant NAFLD association was observed for PNPLA3 (rs738409) [OR = 1.25, 95% CI 1.08–1.44, P = 0.003)]; rs738409 was also associated with a trend towards lower serum triglycerides APOC3 variants were significantly (P = 7.3–7.5 × 10–8) associated with higher triglycerides, but not with NAFLD (OR = 0.86). Apart from SNP–lipid associations previously reported at the GCKR, PPP1R3B and NCAN loci, there were no other prominent associations. Conclusion: Our data confirm that the PNPLA3 gene variant is significantly associated with NAFLD in the general Sri Lankan population but could not replicate previously-reported disease associations at other loci, reinforcing the importance 上海皓元 of further large-scale study on genetic variants in diverse populations to better understand the pathophysiology of NAFLD. Key Word(s): 1. Fatty liver; 2. Genetics; 3. Genetic variants; Presenting

Author: JINHUI WANG Additional Authors: YUNING CHEN, JIE CHEN, MINHU CHEN Corresponding Author: JINHUI WANG Affiliations: the first affilliated hospital of Sun Yatsen University; the first affiliated hospital of Sun Yet-Sen University; the fisrt affiliated hospital of Sun Yatsen University Objective: Background: it is still controversy and unknown about the profile of clinical characters and prognosis among subtypes of Wilson’s disease (WD), as well as its associations with the sera biochemical index. Aim: to learn and evaluate the difference of the clinical characters and prognosis among the different subtypes of Wilson’s disease (WD).

Biweekly MRI examinations followed to determine volumetric changes in tumor size between the two arms compared with the initial rate of tumor growth (Fig. 5A). After only 2 weeks of treatment, the MRI at week 4 showed a significant difference in volume between the two arms, with the MEK inhibitor arm regressing in volume (vehicle = 108.5% ± 5.3%, PD0325901 = 53.9% ± 9.3%, P < 0.02). The next MRI at week 6 continued to show a significant selleck products difference in tumor volume between the two arms, with the PD0325901 arm demonstrating further

regression in tumor volume (vehicle = 136.3% ± 10.5%, PD0325901 = 51.4% ± 10.2%, P < 0.001). The next series of MRI images at week 8 demonstrated tumor growth with vehicle treatments (141.7 %) and continued regression in tumor volume with PD0325901 (55.9% ± 19.5%). Apoptosis was significantly induced in the PD0325901 arm compared with the vehicle Tyrosine Kinase Inhibitor Library cell line arm (Fig. 5B). Some mortality was observed in both arms of this study, most likely because of the stress of undergoing the MRI procedure in combination with drug treatment. Similar tumor regression was detected by MRI after treatment with a lower dose

of PD0325901 (10 mg/kg; data not shown), Current chemotherapy for HCC has had little success in treating this disease. The future direction of chemotherapy is to target specific pathways that are known to be involved in the particular cancer. The ERK/MAPK pathway is up-regulated in most human HCC tumors; thus, targeting this pathway could suppress tumor growth and in turn increase the life span of HCC patients. Prior attempts at targeting the MEK-ERK 上海皓元 signaling cascade have not proved successful in human trials and have led to the development of newer, more bioavailable MEK inhibitors. PD0325901, a derivative of CI-1040, is potent at nanomolar concentrations

and has greater duration, potency, and solubility, resulting in improved bioavailability and increased metabolic stability over CI-1040.28 The inhibitor binds to MEK1/2 at a non–adenosine triphosphate binding site, causing conformational changes that prevent it from phosphorylating ERK, making it a highly selective inhibitor.28 The current study employed TAMH cells, an immortalized line obtained from the MT42 (CD-1) TGF-α transgenic mouse, as well as HepG2 and Hep3B human HCC cells. In all three cell lines, we demonstrated that PD0325901 effectively reduced P-ERK levels and cell growth in vitro, with effects seen in the nanomolar range. Growth inhibition was associated with the induction of apoptosis in HepG2 and Hep3B cells in vitro. PD0325901 also inhibited TAMH and Hep3B tumor growth in an athymic mouse model in vivo. TAMH flank tumors showed decreases in P-ERK levels 24 hours after a single dose of PD0325901 compared with vehicle control, confirming inhibition of the MEK-ERK pathway.

4M0.75; where M is body mass in kg), and 3 ×  Kleiber. Facing an increase in drag, an individual can: (1) maintain a characteristic velocity and exponentially increase energy expenditure to overcome added drag; or (2) swim at

a reduced speed in order to maintain GW-572016 in vitro the same power output as if under normal conditions (Jones et al. 2011). For the latter case, the decrease in velocity (Ured, m/s) to maintain the same power output in an entangled drag scenario (DT), is (12) To determine the additional power demands experienced by Eg 3911 while entangled, we compared PI,T for the drag conditions of a nonentangled whale, with surface drag factor γ following disentanglement (i.e., γ  =  1.0), to the conditions of an entangled whale, towing three gear configurations tested in this experiment, with surface drag factor g calculated for the mean ± SD dive

Venetoclax depth prior to disentanglement (i.e., γ  =  1.6). Dive Parameters—Eg 3911 completed n = 152 dives over the 6 h deployment period, to a median (IQR) depth of 11.50 (10.97) m and duration of 98.7 (82.1) s (Fig. 5). Within the Sedation/Entangled phase, there was no significant difference between the depth or duration of dives completed in the 21 min prior to (n = 7) and the 50 min following (n = 45) sedative injection (Z = 0.402 and 0.188; P = 0.6876 and 0.8511, respectively; Table 3). Dive depth increased significantly with every phase (χ2 = 26.66, P < 0.0001; Fig. 6). Median

dive depth was significantly (138%) shallower in Sedation/Entangled compared to Disentangled (Z  =  −6.121, P < 0.0001). Significant increases in dive depth occurred between Disentangled and Recovery (Z = 4.607, P < 0.0001), though only by 19%. Even when considering increases in approximate regional MCE water column depth with time, proportional dive depth was significantly shallower in Sedation/Entangled (by 95%) compared to following the removal of gear and buoys (i.e., in Disentangled; Z  =  −5.216, P < 0.0001; Fig. 6). Further, we observed no significant difference in proportional dive depth between Disentangled and Recovery phases (Z  =  −0.679, P = 0.497). Descent rates (m/s) during dives differed significantly between phases (χ2 = 49.87, P < 0.0001; Fig. 6), where descents during Sedation/Entanglement were 57% slower than in Disentangled (Z  =  −6.287, P < 0.0001). There was no significant difference between the descent rates in Disentangled and Recovery (Z = 0.535, P = 0.5927). Ascent rates (m/s) during dives also differed significantly between phases (χ2 = 46.22, P < 0.0001; Fig. 6), with significantly slower ascents (31%) during Sedation/Entanglement compared to in Disentanglement (Z  =  −5.948, P < 0.0001). Similar to descent rate, ascent rate did not differ between Disentanglement and Recovery (Z = 0.090, P = 0.9285). For Eg 3911 (h = 1 m, d = 2.20 m), wave drag is maximal within 0.