This paper highlights a hitherto unreported change in progress among northern speakers of British English, with increasing post-nasal ɡ-presence in words like sing or wrong pre-pausally. The factors ...that condition this innovation are unclear due to collinearity between various boundary phenomena. The right edge of phrasal prosodic categories may be associated with boundary tones, final lengthening, and pause; consequently, the variable presence of ɡ appears to be affected by prosodic boundary strength, segmental duration, and the presence and duration of a following pause. These factors are teased apart through analysis of an elicitation task from 30 northern speakers, which reveals that ŋɡ clusters are conditioned most strongly by pause. Post-nasal ɡ-presence is only licensed when the following consonant-initial word is temporally distant, showing only minimal sensitivity to prosodic boundaries directly. The surface effect of segmental duration arises only indirectly through its collinearity with pause duration. Current theoretical approaches to external sandhi emphasize a range of different factors, including phonological representations of prosodic constituency, phonetic parameters like segmental duration, and psycholinguistic mechanisms of production planning. This paper provides quantitative evidence from an under-reported feature of northern English that bears directly on these debates.
Purpose Collagenase clostridium histolyticum is approved for the treatment of Peyronie’s disease. To date, no post-release study to our knowledge has evaluated patient perceived outcomes and ...satisfaction. Therefore, we evaluated patient perceived experience with collagenase clostridium histolyticum injection for Peyronie’s disease in a clinical practice. Materials and Methods From March 2014 to July 2015, 69 patients underwent 1 to 4 series of collagenase clostridium histolyticum injections for Peyronie’s disease at our institution. Objective changes in penile curvature as well as patient reported functional outcomes and patient perceived curvature improvements were evaluated. Results By the time of analysis 31 patients (45%) had completed 4 trials, 47 (68%) completed 3 trials and 59 (86%) completed 2 trials. Patient reported improvements (percentage) in curvature increased with each series (trial 1—14%, trial 2—28%, trial 3—30% and trial 4—37%, p <0.05). Among those completing therapy 57% reported that collagenase clostridium histolyticum injections negated a need for surgery and 52% reported restoration of penetration. Overall 81% of men perceived collagenase clostridium histolyticum treatment as meaningful and 88% reported subjective improvements after 4 series of injections. Objective measures demonstrated a mean 23-degree curvature improvement (38%, p <0.0001). Seven patients (10%) experienced penile hematomas and no patients experienced tunical rupture. Conclusions Collagenase clostridium histolyticum reduced the need for surgery and restored penetration in the majority of patients completing 4 series of injections. It also significantly reduced the degree of objectively measured penile curvature. Subjective improvements in curvature increased with each series of collagenase clostridium histolyticum injections as well and the majority of patients considered the therapy worthwhile.
We investigated the perception of higher-order interpersonal affordances for kicking that emerged from lower-order personal and interpersonal affordances in the context of soccer. Youth soccer ...players reported the minimum gap width between two confederates through which they could kick a ball. In Experiment 1, we independently manipulated the egocentric distance of gaps from participants, and the nominal role of the confederates, either as teammates or opponents. In Experiment 2, we additionally varied the direction in which the confederates were facing, either together (i.e., into the gap) or away (i.e., away from the gap). Perceived minimum kickable gap width was larger for farther egocentric distances, when confederates were identified as opponents rather than as teammates, and (in Experiment 2) when confederates faced toward, rather than away from the gap. In both experiments, these main effects were subsumed in statistically significant interactions. We argue that these interactions reveal perception of higher-order interpersonal affordances for kicking that emerged from the simultaneous influence of lower-order affordances. The results are compatible with the hypothesis that these higher-order affordances were perceived, as such, and were not additively combined from independent perception of underlying, lower-order affordances.
Public Significance StatementPerception of action possibilities informs everyday action, such as deciding whether we can kick the ball between two players in a soccer game. This study demonstrated that young soccer players can directly apprehend how their kicking ability is simultaneously influenced by different kinds of factors, and that they do not have to "figure out" how the different factors relate to each other. This is evidence of a fundamental unity between perception and cognition.
Background
The high prevalence of chronic diseases, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM), accounts for a large burden of ...cost and poor health outcomes in US hospitals, and home telehealth (HT) monitoring has been proposed to improve outcomes.
Objective
To measure the association between HT initiation and 12-month inpatient hospitalizations, emergency department (ED) visits, and mortality in veterans with CHF, COPD, or DM.
Design
Comparative effectiveness matched cohort study.
Patients
Veterans aged 65 years and older treated for CHF, COPD, or DM.
Main Measures
We matched veterans initiating HT with veterans with similar demographics who did not use HT (1:3). Our outcome measures included a 12-month risk of inpatient hospitalization, ED visits, and all-cause mortality.
Key Results
A total of 139,790 veterans with CHF, 65,966 with COPD, and 192,633 with DM were included in this study. In the year after HT initiation, the risk of hospitalization was not different in those with CHF (adjusted odds ratio aOR 1.01, 95% confidence interval 95%CI 0.98–1.05) or DM (aOR 1.00, 95%CI 0.97–1.03), but it was higher in those with COPD (aOR 1.15, 95%CI 1.09–1.21). The risk of ED visits was higher among HT users with CHF (aOR 1.09, 95%CI 1.05–1.13), COPD (1.24, 95%CI 1.18–1.31), and DM (aOR 1.03, 95%CI 1.00–1.06). All-cause 12-month mortality was lower in those initiating HT monitoring with CHF (aOR 0.70, 95%CI 0.67–0.73) and DM (aOR 0.79, 95%CI 0.75–0.83), but higher in COPD (aOR 1.08, 95%CI 1.00–1.16).
Conclusions
The initiation of HT was associated with increased ED visits, no change in hospitalizations, and lower all-cause mortality in patients with CHF or DM, while those with COPD had both higher healthcare utilization and all-cause mortality.
Introduction
Inhaled methoxyflurane is an analgesic used for the emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain that is increasingly being ...used in hospital emergency departments to provide rapid analgesia. It is widely accepted that effective pain relief can facilitate patient care and flow through the emergency department (ED). The main aim of this evaluation was to assess the impact of inhaled methoxyflurane on patient length of stay (LOS) in the ED compared with standard care.
Methods
Adult patients with moderate to severe trauma pain and Glasgow coma score of 15 were included in the evaluation. Evaluation forms were completed for 79 patients who received methoxyflurane and were matched with 80 patients who received standard care.
Results
Overall the mean time spent in the ED was reduced by 71 min in those patients who were administered methoxyflurane compared with patients who received standard care. Furthermore, analysis of LOS by injury type demonstrated a reduction in ED LOS by 183 min for patients with shoulder dislocation who were treated with methoxyflurane compared with patients who received standard care. There was no reduction in ED LOS for patients with lower limb, hip or pelvic injuries between the two treatment groups.
Conclusion
Use of methoxyflurane in adult patients with trauma pain significantly reduced the ED LOS and may potentially improve patient flow through the ED.
Purpose To our knowledge there are no guidelines for the evaluation and management of incontinence in women with an orthotopic neobladder. We propose a treatment algorithm based on our experience ...with treating this patient population. Materials and Methods We identified women in whom orthotopic neobladder diversion and surgery for incontinence were performed from January 1, 1995 to January 1, 2014. Charts were reviewed for management, outcomes and complications within 30 days of surgery. Results At this institution 12 women with orthotopic neobladder diversion were treated with surgery for incontinence between 1995 and 2014. Six women (50%) had an undiagnosed neovesicovaginal fistula, of whom 3 (50%) underwent successful fistula repair. A total of 12 bulking agent injections were performed in 6 women (50%). The outcomes were continued dryness after 1 injection (8%), transient improvement after 9 (75%), immediate failure after 1 (8%) and secondary fistula development after 1 (8%). Four transobturator slings and 4 pubovaginal slings were placed in a total of 6 patients (50%), of whom 1 (17%) was dry and 1 (17%) was improved. At a median followup of 22.9 months (IQR 11.1–46.4) 6 women (50%) were dry or improved and 6 (50%) had no improvement in leakage. Of the 6 (50%) women who were dry or improved 2 (17%) achieved planned intermittent catheterization after surgery and 2 (17%) underwent ileal conduit conversion. Conclusions Bulking agents have low long-term efficacy and carry the risk of fistula formation. The efficacy of tension-free sling placement is low and continence requires an obstructing sling. Counseling should include acceptance of multiple procedures, which may be necessary to achieve continence, and consideration of conduit diversion.
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Acalabrutinib (Calquence®) 100 mg (bid) has received accelerated approval by FDA for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one ...prior therapy. Acalabrutinib is a substrate of PgP and CYP3A4, with a significant fraction of drug metabolized by first pass gut extraction and 25% absolute bioavailability. The absorption of acalabrutinib is affected by stomach pH, with lower pharmacokinetic exposure observed following co-administration with proton pump inhibitors.
During dissolution at pH values below its highest basic pKa, the two basic moieties of acalabrutinib react with protons from the aqueous solution, leading to a higher pH at the drug surface than in the bulk solution. A batch-specific product particle size distribution (P-PSD), was derived from dissolution data using a mechanistic model that was based on the understanding of surface pH and the contribution of micelles to the dissolution rate. P-PSD values obtained for various batches of acalabrutinib products in simple buffers, or in complex fluids such as fruit juices, were successfully integrated into a physiologically based pharmacokinetic (PBPK) model developed using GastroPlus v9.0™. The integrated model allowed the prediction of clinical pharmacokinetics under normal physiological stomach pH conditions as well as following treatment with proton pump inhibitors. The model also accounted for lower pharmacokinetic exposure that was observed when acalabrutinib was co-administered with the acidic beverages, grapefruit juice, (which contains CYP3A inhibitors), and orange drink (which does not contain CYP3A inhibitors), relative to administration with water.
The integration of dissolution data in the PBPK model enables mechanistic understanding and the establishment of more robust in vitro-in vivo correlations (IVIVC) under a variety of conditions. The model can then distinguish the interplay between dissolution and first pass extraction and how in vivo stomach pH, saturation of gut PgP, and saturation or inhibition of gut CYP3A4, will impact the pharmacokinetics of acalabrutinib.
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