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Water quality standards programs in the United States and other countries are based on designated uses (DUs), which are linked to criteria that specify maximum pollutant levels and other characteristics that are thresholds for waterbody compliance with regulatory goals. Most DUs are similar to certain provisioning ecosystem goods and services (EGS), such as drinking water supply and recreation (e.g., boating, fishing). Absent in the DU concept are supporting or regulating services, which results in disjointed and often ineffective aquatic ecosystem protection and restoration strategies. The focus on discrete sets of water quality parameters in the DU concept can often result in the appearance of conflicting DUs, resulting in poor provisioning of certain DUs. We present a framework that uses EGS to provide a more holistic assessment of DUs and to help inform best management practices that could result in fuller attainment of DUs while providing greater provisioning of desired goods and services. Two case studies are discussed, demonstrating some of the issues with the DU concept, how it is implemented in the United States, and how the EGS framework can provide a crosswalk between the DU paradigm and stakeholder goals for a watershed. A process is presented that could help regulatory agencies and stakeholders make better use of the EGS framework in DU decisions, including watershed protection and restoration. The EGS framework presented here, coupled with a watershed stakeholder process focused on developing an integrative management strategy based on the framework, could help achieve multiple beneficial uses in an aquatic system. Integr Environ Assess Manag 2019;15:808-818. © 2019 SETAC., (© 2019 SETAC.)

Introduction: Dysmenorrhea (period pain) and associated symptoms are very common in young women <25 years. This time corresponds with a significant stage in adolescents and young women's academic lives at both school and in higher education. Dysmenorrhea may cause absenteeism from class or result in reduced classroom concentration and performance. Owing to cultural and economic differences, any impact may vary by country. This systematic review and meta-analysis examines the prevalence of dysmenorrhea in young women and explores any impact it has on their academic performance and other school-related activities. Materials and Methods: A search in Medline, PsychINFO, EMBASE, and Cumulative Index to Nursing and Allied Health Literature was carried out in June 2018. Results: Thirty-eight studies including 21,573 young women were eligible and included in the meta-analysis. Twenty-three studies were from low-, lower middle-, or upper middle-income countries, and 15 studies were from high-income countries. The prevalence of dysmenorrhea was high 71.1% ( N  = 37, n  = 20,813, 95% confidence interval [CI] 66.6-75.2) irrespective of the economic status of the country. Rates of dysmenorrhea were similar between students at school ( N  = 24, 72.5%, 95% CI 67.5-77.0) and at university ( N  = 7, 74.9%, 95% CI 62.9-84.0). Academic impact was significant, with 20.1% reporting absence from school or university due to dysmenorrhea ( N  = 19, n  = 11,226, 95% CI 14.9-26.7) and 40.9% reporting classroom performance or concentration being negatively affected ( N  = 10, n  = 5126, 95% CI 28.3-54.9). Conclusions: The prevalence of dysmenorrhea was high, irrespective of country, with dysmenorrhea having a significant negative impact on academic performance both at school and during higher education.

Introduction: Dysmenorrhea (period pain) is common and affects around three quarters of all young women under the age of 25. The majority of young women, for a variety of reasons, think of period pain as 'normal' and something to be managed or endured. This normalisation of pain often is reinforced by family and friends and results in young women using self-care strategies to manage their pain rather than seeking medical advice. This systematic review and meta-analysis examined observational studies reporting on the prevalence of different types of self-care, both pharmaceutical and non-pharmaceutical, self-rated effectiveness of self-care and the sources of information on menstruation in young women under 25 Methods: A search of Medline, PsychINFO, EMBASE and CINAHL in English was carried out from 1980 to December 2018. Studies that reported on menstrual self-care strategies in young women were included., Results: Nine hundred and forty-seven articles were screened. Twenty-four studies including 12,526 young women were eligible and included in the meta-analysis. Fifteen studies were from low, lower-middle or upper-middle-income countries (LMIC) and nine studies were from high income countries (HIC). Self-care was used by over half of all young women (55%, 95%CI 34.1-74.3) with both pharmaceutical (48%, 95%CI 40.0-57.0) and non-pharmaceutical (51.8%, 95%CI 31.3-71.7) options used. Paracetamol was the most common analgesic used (28.7%, 95%CI 19.6-39.9) but did not always provide sufficient pain relief in almost half of those using it. Contraceptive use was significantly higher (P<0.001) in HIC (22%) compared to LMIC (1%). Only 11% (95%CI 8.4-15.2) of young women reported seeing a medical doctor for their period pain., Conclusions: Self-care usage, both pharmaceutical and non-pharmaceutical, was common, but young women were not necessarily choosing the most effective options for pain management. High-quality information on self-care for period pain is urgently needed., Competing Interests: MA,KP,MaD,CS: As a medical research institute, National Institute of Complementary Medicine (NICM) receives research grants and donations from foundations, universities, government agencies and industry. Sponsors and donors provide untied and tied funding for work to advance the vision and mission of the Institute. This systematic review was not specifically supported by donor or sponsor funding to NICM. CC, KH, TF, FM: The authors have declared that no competing interests exist.

Background: Hiatal hernia (HH) after esophagectomy is becoming more relevant due to improvements in survival. This study evaluated and compared the occurrence and clinical course of HH after open and minimally invasive esophagectomy (MIE)., Methods: The prospectively recorded characteristics of patients treated with esophagectomy for cancer at 2 tertiary referral centers in the United Kingdom and the Netherlands between 2000 and 2014 were reviewed. Computed tomography reports were reviewed to identify HH., Results: Of 657 patients, MIE was performed in 432 patients (66%) and open esophagectomy in 225 (34%). A computed tomography scan was performed in 488 patients (74%). HH was diagnosed in 45 patients after a median of 20 months (range, 0 to 101 months). The development of HH after MIE was comparable to the open approach (8% vs 5%, p = 0.267). At the time of diagnosis, 14 patients presented as a surgical emergency. Of the remaining 31 patients, 17 were symptomatic and 14 were asymptomatic. An elective operation was performed in 10 symptomatic patients, and all others were treated conservatively. During conservative treatment, 2 patients presented as a surgical emergency. An emergency operation resulted in a prolonged intensive care unit stay compared with an elective procedure (3 vs 0 days, p < 0.001). In-hospital deaths were solely seen after emergency operations (19%)., Conclusions: HH is a significant long-term complication after esophagectomy, occurring in a substantial proportion of the patients. The occurrence of HH after MIE and open esophagectomy is comparable. Emergency operation is associated with dismal outcomes and should be avoided., (Copyright © 2017. Published by Elsevier Inc.)

Introduction: Aim of this study was to evaluate the use of Intermittent Pneumatic Compression (IPC) in the prevention of symptomatic venous thromboembolic events (VTE) in patients undergoing esophagectomy for cancer., Methods: From a prospective database, all patients operated between 2010 and 2014 received IPC in addition to LMWH and were compared to a historical cohort of patients treated LMWH only (2004-2009)., Results: Of the 313 included patients, 195 (62%) received IPC. Patients with IPC received neoadjuvant chemoradiation more often (45% vs. 3%, P < 0.001), whereas, neoadjuvant chemotherapy was equally distributed (31% vs. 34%, P = 0.631). There were no differences with regard to surgical approach, operative time, blood loss, and ICU stay. Patients treated without IPC had a longer hospital stay (18 vs. 15 days, P = 0.014). Overall, 12 clinical VTE's occurred in 11 patients, which consisted of two deep venous thromboses and 10 pulmonary embolisms. In the group of patients, who received IPC 1.5% developed a symptomatic VTE compared to 6.8% in patients without IPC (OR = 0.215; 95% CI = 0.06-0.83). Multivariate analysis identified IPC as the only independent prognostic factor correlated with a reduction in postoperative VTE's (OR = 0.225; 95% CI = 0.06-0.88)., Conclusion: The addition of IPC in patients undergoing esophagectomy for cancer was associated with a reduction in symptomatic VTE's. J. Surg. Oncol. 2017;115:181-185. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Minimally invasive techniques in transhiatal esophagectomy (THE) were introduced to reduce morbidity and enhance postoperative recovery. Aim of this study was to systematically review the current status and possible beneficial effects of the minimally invasive approach in THE. A systematic search was performed in PubMed, the Cochrane Library, and Embase to identify English articles published on laparoscopic THE. Comparative cohort studies were included for critical appraisal. Data describing perioperative and oncological outcomes were analyzed. A total of four comparative cohort studies that compared laparoscopic THE (n = 122) with open THE (n = 144) and four noncomparative cohort studies reporting on laparoscopic THE (n = 212) were included in this review. Median blood loss was significantly lower in the laparoscopic group in all studies (100-500 vs. 526-900 mL). Length of hospital stay was also significantly shorter for the laparoscopic approach in all studies (9-13 vs. 12-16 days). One study reported less major postoperative complications after laparoscopic THE (12 vs. 23%), in the other studies no differences were found. Also no differences were found with regard to operating time, postoperative morbidity, radicality, and lymph node retrieval. Based on these pioneer studies, laparoscopic THE was demonstrated to be safe and feasible with evidence of reduced blood loss and shorter hospital stays. However, level 1 evidence is lacking and further research is warranted to confirm these findings and also to evaluate long-term oncologic outcomes., (© 2016 International Society for Diseases of the Esophagus.)

Background: The optimal neoadjuvant approach for patients with adenocarcinomas of the gastroesophageal junction (GEJ) remains unclear. Aim of this study was to evaluate the usefulness of perioperative chemotherapy in these patients., Method: Consecutive patients with GEJ adenocarcinoma, treated with surgery alone or chemotherapy plus surgery, were included from a prospective database (2003-2013). Propensity score matching was used to build comparable groups. Response to chemotherapy was assessed according to standardized regression grading., Results: After propensity score matching, 196 patients were included. Chemotherapy was administered in 124 patients (63%). There was no difference between the chemotherapy plus surgery and surgery-alone group regarding overall and disease-free survival (p = 0.351 and p = 0.529). Pathological good response (i.e. tumor regression grading [TRG] 1-3) was achieved in 32 patients (34%), whereas 81 (66%) had poor response (TRG 4). Good responders had lower ypT-stage (p < 0.001), lower ypN-stage (p < 0.001) and more R0-resections (100% vs. 78%, p = 0.016) compared to surgery-alone patients, which improved the 5-year survival from 35% to 67% (p = 0.002). They also developed less recurrences (35% vs. 57%, p = 0.048). In poor responders, histopathology did not differ compared to surgery-alone and more recurrences were found (73% vs. 57%, p = 0.037). Overall survival in poor responders was 21% compared to 35% in surgery-alone patients (p = 0.551)., Conclusion: Perioperative chemotherapy for GEJ adenocarcinoma leads to increased survival in good responders (34%) as compared to surgery alone. Poor responders had no survival benefit and developed more recurrences, which underlines the importance of the search for predictive biological or radiological markers to predict or assess chemotherapy sensitivity., (Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer., (© 2015 International Society for Diseases of the Esophagus.)

Background: There is no consensus on the optimal technique for hiatal hernia (HH) repair, and considerable recurrence rates are reported. The aim of this study was to evaluate the perioperative outcomes, quality of life (QoL), and recurrence rate in patients undergoing robot-assisted laparoscopic HH repair., Materials and Methods: All patients who underwent robot-assisted laparoscopic HH repair between July 2011 and March 2015 were evaluated. The procedure consisted of hernia sac reduction, crural repair without mesh, and Toupet fundoplication. Postoperative radiological imaging or endoscopy was performed in all symptomatic patients to exclude recurrence. Perioperative results were collected retrospectively from the patient records. QoL was evaluated with Short Form-36 (SF-36), Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQOL), and Gastrointestinal Quality of Life Index (GIQLI) questionnaires., Results: A total of 40 patients were identified. The majority (75%) had a type III HH. Median operation time was 118 (62-173) minutes; median blood loss was 20 (10-934) mL, and one procedure was converted to an open procedure. In 6 (15%) patients, postoperative complications occurred, including 2 grade II and 1 grades I, III, IV, and V, according to the Clavien-Dindo classification. Median hospital stay was 3 (1-15) days. At a median follow-up of 11 months, radiological imaging was performed on indication in 12 (30%) patients, and 1 recurrence was found. Overall QoL scores were satisfactory, and there was no difference related to the time elapsed since surgery., Conclusion: Robot-assisted laparoscopic HH repair followed by Toupet fundoplication demonstrated a very low short-term recurrence rate. Postoperative morbidity was minimal, and a satisfactory QoL was achieved.

Background: Resectable gastroesophageal junction (GEJ) tumors are treated either with an esophageal-cardia resection or with gastrectomy. The difference in outcome between these two treatment modalities is unknown; Therefore, the aim of this study was to evaluate population-based treatment strategies for patients with resectable adenocarcinomas of the GEJ and to compare the oncological outcomes., Methods: Patients with potentially resectable GEJ tumors diagnosed between 2005 and 2012 were selected from the nationwide, population-based Netherlands Cancer Registry. Differences between patients were compared using the χ (2) test, and survival curves were generated using the Kaplan-Meier method. Overall multivariate survival was assessed using Cox regression analyses., Results: Patients treated with esophagectomy (n = 939) were significantly younger than patients treated with gastrectomy (n = 257; 64 vs. 66 years; p < 0.001), and no differences were noted regarding lymph node yield, lymph node ratio, and radicality. Patients treated with an esophagectomy or gastrectomy exhibited comparable overall 5-year survival rates (36 vs. 33 %, respectively; p = 0.250). Multivariate analysis showed that patients receiving perioperative treatment and gastrectomy exhibited similar overall survival rates compared with patients receiving perioperative treatment and esophagectomy [hazard ratio (HR) 1.9, 95 % confidence interval (CI) 0.7-1.3; p = 0.908]; however, patients receiving esophagectomy alone (HR 1.3, 95 % CI 1.3-1.8; p = 0.002) or gastrectomy alone (HR 1.8, 95 % CI 1.4-2.4; p < 0.001) exhibited a significantly worse overall survival., Conclusions: The chosen type of surgery (esophagectomy or gastrectomy) did not influence the overall survival in our cohort of patients with GEJ tumors. The administration of perioperative chemo(radio)therapy improved survival regardless of the surgical approach.

Background: Clinical staging of adenocarcinoma of the gastroesophageal junction (GEJ) determines the curative treatment regimen containing either neoadjuvant chemotherapy or chemoradiotherapy followed by either gastrectomy or esophagectomy. The value of current diagnostic tools is a matter of debate., Methods: A prospective database (2003-2013) was used to identify 266 consecutive patients with adenocarcinoma of the GEJ in order to evaluate the accuracy of endoscopic ultrasound (EUS) and computed tomography (CT) regarding tumor localization according to Siewert, nodal status and its consequences on treatment strategy., Results: Overall accuracy in determining tumor localization was 73% for endoscopy/EUS and 61% for CT (p = 0.018). With endoscopy/EUS, the accuracy was 97%, 66% and 75% respectively for type I, II and III. With CT this was respectively 69%, 57% and 80%. The overall accuracy for determining N-status (N0/N+) per patient was 75% for EUS and 71% for CT. Accuracy for determining a positive nodal station in patients without neoadjuvant therapy was 77% for EUS and 71% for CT (p = 0.001). Accuracy for detecting positive upper mediastinal nodes was 80-92%, whereas for peritumoral and abdominal nodes this was 50-80% in both EUS and CT. In 8/266 patients (3%) the type of surgery changed due to intraoperative findings. A radical resection was performed in 233 patients (88%)., Conclusions: Despite the suboptimal accuracy of determining tumor localization with EUS and CT, in only a small number of patients an intraoperative change of surgical treatment was needed. EUS is superior to CT in determining nodal status and tumor localization in GEJ tumors., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Strategies for the treatment of recurrence after initial curative esophagectomy are increasingly being recognized. The aim of this study was to identify prognostic factors that affect survival in patients with recurrence and to evaluate treatment strategies., Methods: A prospective database (2003-2013) was used to collect consecutive patients with esophageal carcinoma treated with initial curative esophagectomy. Locations, symptoms, and treatment of recurrence were registered. Post-recurrence survival was defined as the time between the first recurrence and death or last follow-up., Results: Of the 335 selected patients, 171 (51 %) developed recurrence. Multivariable analysis identified distant recurrence as opposed to locoregional recurrence [hazard ratio (HR) 2.15, 95 % confidence interval (CI) 1.27-3.65; p = 0.005], more than three recurrent locations (HR 2.42, 95 % CI 1.34-4.34; p = 0.003), and treatment (HR 0.29, 95 % CI 0.20-0.44; p < 0.001) as independent prognostic factors associated with post-recurrence survival. Primary tumor characteristics, including neoadjuvant therapy, histological type, pTN stage, and radicality, did not independently influence post-recurrence survival. Treatment was initiated in 62 patients (37 %) and included chemotherapy, radiotherapy, and/or surgery. Median post-recurrence survival of all patients was 3.0 months (range 0-112). In total, six patients (4 %) were still disease-free following treatment, indicating cure., Conclusions: In patients treated for esophageal cancer at curative intent, distant recurrence and more than three recurrent locations were independent prognostic factors associated with worse post-recurrence survival, irrespective of primary tumor characteristics. Although survival after recurrence was poor, treatment can prolong survival and can even lead to cure in selected patients.

Background & Aims: Hirschsprung's disease (HD) is a rare birth defect of the distal colon. Analysis of rectal suction biopsy (RSB) is considered to be the most reliable method for its diagnosis in infants. However, the diagnostic accuracy of RSB analysis could be affected by the patient's age, possibly because of rapid development of the enteric nervous system in the first weeks after birth. Because there is a trend toward testing for HD at early ages, we aimed to determine whether the diagnostic accuracy of RSB analysis is associated with the patient's age., Methods: We performed a retrospective analysis of all patients from whom 1 or more RSBs were analyzed from 1975 through 2011 (529 RSBs from 441 patients). Outcomes of RSB analyses were categorized as positive, inconclusive, or negative for HD. Primary diagnoses, based only on RSB, were compared with final diagnoses made after at least 1 year of clinical follow-up. Age at time of RSB analysis was corrected for the gestational age. By using these criteria, we determined the diagnostic accuracy of RSB analysis for different age groups., Results: RSB analysis identified HD in patients with sensitivity values of 46% (patients -45 to 7 days old), 47% (8-22 days old), and 62% (23-39 days old) (corrected for gestational age). The average sensitivity with which RSB analysis identified HD in patients older than 39 days was 88%. RSB identified HD in patients younger than 39 days old with significantly lower sensitivity than in older patients (50% vs 88%, P < .001). The specificity with which RSB identified infants without HD was not affected by age (average 95%). Of all RSBs, 11% were inconclusive for the diagnosis of HD., Conclusions: RSB analysis identifies HD in patients younger than 39 days old with only 50% sensitivity. Moreover, RSBs obtained from younger patients often lead to inconclusive outcomes and require additional biopsies. We propose that for infants suspected of HD at these ages, a noninvasive technique, such as anorectal manometry, should be used for a primary diagnosis. RSB should thereafter be used to confirm the diagnosis when the infant is older than 39 days., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Background: Patients with adenocarcinoma of the gastro-esophageal junction (GEJ) may undergo either esophagectomy or gastrectomy. The aim of this study was to evaluate the outcome of surgical therapy with regard to postoperative outcome and survival in patients with Siewert type II tumors., Methods: A prospective database of 266 consecutive patients with surgically resectable GEJ adenocarcinomas from 2003 to 2013 was analyzed. The surgical approach was based on preoperative imaging and intraoperative findings., Results: According to the histopathological analysis, 67 patients (25 %) had type I tumor, 176 patients (66 %) had type II tumor, and 16 patients (6 %) had type III tumor. In total, 86 % were treated with esophagectomy and 14 % with gastrectomy. Overall 5-year survival was 38 %. In type II patients, the type of operation did not significantly influence overall survival on multivariate analysis (p = 0.606). A positive circumferential resection margin (CRM) at the site of the esophagus was more common with gastrectomy (29 vs. 11 %; p = 0.025). No significant differences in mortality, morbidity, or disease recurrence were found. In patients with type II tumors, upper mediastinal nodal involvement (subcarinal, paratracheal, and aortapulmonary window) was found in 11 % of the patients. In 34 % of patients treated with esophagectomy, paraesophageal lymph nodes metastases were harvested compared with 5 % of patients treated with gastrectomy., Conclusions: In patients with a type II GEJ adenocarcinoma, a positive CRM was more common with gastrectomy. Esophagectomy provides for a more complete para-esophageal lymphadenectomy. Furthermore, the high prevalence of mediastinal nodal involvement indicates that a full lymphadenectomy of these stations should be considered.

The Vesicle-associated membrane protein (VAMP)-Associated Protein B (VAPB) is the causative gene of amyotrophic lateral sclerosis 8 (ALS8) in humans. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of motor neurons leading to spasticity, muscle atrophy and paralysis. VAP proteins have been implicated in various cellular processes, including intercellular signalling, synaptic remodelling, lipid transport and membrane trafficking and yet, the molecular mechanisms underlying ALS8 pathogenesis remain poorly understood. We identified the conserved phosphoinositide phosphatase Sac1 as a Drosophila VAP (DVAP)-binding partner and showed that DVAP is required to maintain normal levels of phosphoinositides. Downregulating either Sac1 or DVAP disrupts axonal transport, synaptic growth, synaptic microtubule integrity and the localization of several postsynaptic components. Expression of the disease-causing allele (DVAP-P58S) in a fly model for ALS8 induces neurodegeneration, elicits synaptic defects similar to those of DVAP or Sac1 downregulation and increases phosphoinositide levels. Consistent with a role for Sac1-mediated increase of phosphoinositide levels in ALS8 pathogenesis, we found that Sac1 downregulation induces neurodegeneration in a dosage-dependent manner. In addition, we report that Sac1 is sequestered into the DVAP-P58S-induced aggregates and that reducing phosphoinositide levels rescues the neurodegeneration and suppresses the synaptic phenotypes associated with DVAP-P58S transgenic expression. These data underscore the importance of DVAP-Sac1 interaction in controlling phosphoinositide metabolism and provide mechanistic evidence for a crucial role of phosphoinositide levels in VAP-induced ALS.

Background: Exclusive breastfeeding for 6 months and continued breastfeeding for at least 1 year is recommended by all major health organizations. Whereas 74.6 percent of mothers initiate breastfeeding at birth, exclusivity and duration remain significantly lower than national goals. Empirical evidence suggests that exposure to infant formula marketing contributes to supplementation and premature cessation. The objective of this study was to explore how women interpret infant formula advertising to aid in an understanding of this association., Methods: Four focus groups were structured to include women with similar childbearing experience divided according to reproductive status: preconceptional, pregnant, exclusive breastfeeders, and formula feeders. Facilitators used a prepared protocol to guide discussion of infant formula advertisements. Authors conducted a thematic content analysis with special attention to women's statements about what they believed the advertisements said about how the products related to human milk (superior, inferior, similar) and how they reported reacting to these interpretations., Results: Participants reported that the advertisements conveyed an expectation of failure with breastfeeding, and that formula is a solution to fussiness, spitting up, and other normal infant behaviors. Participants reported that the advertisements were confusing in terms of how formula-feeding is superior, inferior or the same as breastfeeding. This confusion was exacerbated by an awareness of distribution by health care practitioners and institutions, suggesting provider endorsement of infant formula., Conclusions: Formula marketing appears to decrease mothers' confidence in their ability to breastfeed, especially when provided by health care practitioners and institutions. Therefore, to be supportive of breastfeeding, perinatal educators and practitioners could be more effective if they did not offer infant formula advertising to mothers., (© 2013, Copyright the Authors, Journal compilation © 2013, Wiley Periodicals, Inc.)

Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by selective death of motor neurons leading to spasticity, muscle wasting and paralysis. Human VAMP-associated protein B (hVAPB) is the causative gene of a clinically diverse group of MNDs including amyotrophic lateral sclerosis (ALS), atypical ALS and late-onset spinal muscular atrophy. The pathogenic mutation is inherited in a dominant manner. Drosophila VAMP-associated protein of 33 kDa A (DVAP-33A) is the structural homologue of hVAPB and regulates synaptic remodeling by affecting the size and number of boutons at neuromuscular junctions. Associated with these structural alterations are compensatory changes in the physiology and ultrastructure of synapses, which maintain evoked responses within normal boundaries. DVAP-33A and hVAPB are functionally interchangeable and transgenic expression of mutant DVAP-33A in neurons recapitulates major hallmarks of the human diseases including locomotion defects, neuronal death and aggregate formation. Aggregate accumulation is accompanied by a depletion of the endogenous protein from its normal localization. These findings pinpoint to a possible role of hVAPB in synaptic homeostasis and emphasize the relevance of our fly model in elucidating the patho-physiology underlying motor neuron degeneration in humans.

Background: The processes by which eggs develop in the insect ovary are well characterized. Despite a large number of Drosophila mutants that cannot lay eggs, the way that the egg is moved along the reproductive tract from ovary to uterus is less well understood. We remedy this with an integrative study on the reproductive tract muscles (anatomy, innervation, contractions, aminergic modulation) in female flies., Results: Each ovary, consisting of 15-20 ovarioles, is surrounded by a contractile meshwork, the peritoneal sheath. Individual ovarioles are contained within a contractile epithelial sheath. Both sheaths contain striated muscle fibres. The oviduct and uterine walls contain a circular striated muscle layer. No longitudinal muscle fibres are seen. Neurons that innervate the peritoneal sheath and lateral oviduct have many varicosities and terminate in swellings just outside the muscles of the peritoneal sheath. They all express tyrosine decarboxylase (required for tyramine and octopamine synthesis) and Drosophila vesicular monoamine transporter (DVMAT). No fibres innervate the ovarioles. The common oviduct and uterus are innervated by two classes of neurons, one with similar morphology to those of the peritoneal sheath and another with repeated branches and axon endings similar to type I neuromuscular junctions. In isolated genital tracts from 3- and 7-day old flies, each ovariole contracts irregularly (12.5 +/- 6.4 contractions/minute; mean +/- 95% confidence interval). Peritoneal sheath contractions (5.7 +/- 1.6 contractions/minute) move over the ovary, from tip to base or vice versa, propagating down the oviduct. Rhythmical spermathecal rotations (1.5 +/- 0.29 contractions/minute) also occur. Each genital tract organ exhibits its own endogenous myogenic rhythm. The amplitude of contractions of the peritoneal sheath increase in octopamine (100 nM, 81% P < 0.02) but 1 microM tyramine has no effect. Neither affects the frequency of peritoneal sheath contractions., Conclusion: The muscle fibres of the reproductive tract are circular and have complex bursting myogenic rhythms under octopaminergic neuromodulation. We propose a new model of tissue-specific actions of octopamine, in which strengthening of peritoneal sheath contractions, coupled with relaxation of the oviduct, eases ovulation. This model accounts for reduced ovulation in flies with mutations in the octopaminergic system.

Difficulty with intubation, ventilation or both is a significant issue for anaesthetists. The American Society of Anesthesiologists' Guidelines for the Management of the Difficult Airway is an algorithm widely used when airway difficulties are encountered. Ideally, anaesthetic trainees should have access to simulators suitable for learning and practising how to manage airway difficulties, but most models have been designed primarily for resuscitation training. The aim of this study was to determine which small airway simulators could be used to practise steps in the Difficult Airway Algorithm (DAA). We identified the essential elements of the DAA relating to endotracheal intubation (laryngoscope, Trachlight and Fastrach), external laryngeal manipulation, dedicated airway devices (LMA, Combitube) and trans-tracheal ventilation using the Enk oxygen flow modulator (Cook). Each element was studied in adult airway models sold for airway management training. The DAA elements were studied in 16 different airway models. No single model achieved our criteria of "good/very realistic" for all elements. All elements of the DAA could be used in the Difficult Airway Trainer Deluxe (MPL) and Bill (VBM/Mallinckrodt) but it would be necessary to acquire at least two trainers to achieve "good/very realistic" in all techniques studied. Anaesthetic departments planning to acquire small simulators for airway management training should undertake a training-needs analysis and apply this to the performance characteristics of the simulators. Generally, at least two airway training models will be needed to teach all steps of the DAA effectively.

Aim: To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma., Design of Study: Randomised controlled trial in four schools; parallel observational study in two schools., Setting: Six comprehensive schools., Method: In the randomised trial, pupils were invited to attend asthma review at a nurse-led clinic either in school, or in general practice. The parallel observational study compared pupils invited to practice care within and outside the randomised trial. Primary outcome measures were attendance for asthma review, symptom control, and quality of life. Secondary outcomes were knowledge, attitudes, inhaler technique, use of steroids, school absence, peak flow rate, preference for future care, health service utilisation, and costs., Results: School clinic pupils were more likely to attend an asthma review than those randomised to practice care (90.8% versus 51.0% overall [P < 0.001, not consistent across schools]). No differences were observed in symptom control (P = 0.42) or quality of life (P = 0.63). Pupils attending school clinics had greater knowledge of asthma (difference = +0.38, 95% CI = 0.19 to 0.56), more positive attitudes (difference = +0.21, 95% CI = 0.05 to 0.36), and better inhaler technique (P < 0.001, not consistent across all schools). No differences were observed in school absence or peak flow rate. A majority (63%) of those who had received care at school preferred this model in future. Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds, respectively. No differences were observed between the groups in the observational comparison on any outcome., Conclusions: The schools asthma clinic increased uptake of asthma reviews. There were improvements in various process measures, but not in clinical outcomes.

Objective: To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking "same day" consultations in primary care., Design: Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day)., Setting: 10 general practices in south Wales and south west England., Subjects: 1368 patients requesting same day consultations., Main Outcome Measures: Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future., Results: Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer., Conclusion: This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.

Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have been shown to be genotoxic in vivo and in vitro. We present a cytogenetic collaborative study on 13 cancer patients treated with different antitumor agents. For comparison we also carried out a cytogenetic analysis on 14 healthy untreated controls. The frequency of sister chromatid exchanges and structural chromosome aberrations in peripheral blood lymphocytes of the cancer patients was determined prior to the treatment, just after it and 3-7 weeks later. The results obtained show clear differences between the basal levels of cytogenetic alterations in cancer patients, even though the mean value is higher in this group than the basal levels of the group of healthy individuals. Treatment with cytostatics increases the frequency of both cytogenetic biomarkers analyzed, which declined to values similar to those initially observed several weeks after the treatment. Our data are in qualitative and quantitative agreement with other results previously found by other authors.

Background: A retrospective study of 138 children with Tourette's syndrome for associated school problems revealed that at the time of initial evaluation, 64 subjects (46%) experienced a school-related problem., Objective: To survey a childhood population with Tourette's syndrome to explore the contributions of neurobehavioral concomitants to academic difficulties., Results: A diagnosis of a specific learning disorder had previously been made in 30 (22%) of 138 children. Among the 108 without a diagnosis of learning disorder, 36 (33%) experienced school difficulties defined as grade retention (16 [15%]) and/or special education placement (41 [38%]). Regression analysis of subjects without a diagnosis of learning disability revealed that the presence of attention-deficit hyperactivity disorder served as a significant predictor of school problems., Conclusions: Tics represented the primary reason for referral, but did not emerge as a significant predictor of academic problems. Rather, school-related difficulties appeared to be strongly associated with comorbid attention-deficit hyperactivity disorder.

A case of empyema and lung abscess in an elderly patient who presented with clinical features of congestive cardiac failure is described. Gemella morbillorum was cultured from pleural exudate found postmortem to be associated with a lung abscess. To our knowledge this is the first reported case of infection with this organism in this setting. We discuss the clinical spectrum and management of infection with this infrequently encountered organism.

A survey of the education in terminal care received by a wide range of doctors in Scotland showed that clinical instruction in the physical and emotional aspects of the care of the dying had been generally inadequate, and that the educational influence of a special unit or hospice could be significant. Doctors who had undertaken traineeships in general practice tended to have had more comprehensive training in terminal care-and to be more enthusiastic about further education-than others. We conclude that planned vocational training schemes in all disciplines need to be re-examined for the provision they make for education in terminal care, and that continuing education in the subject may need to be improved for all doctors.

Domestic fowl, ducks, geese, Guinea-fowl, quail and pigeons were anaesthetised with intravenous pentabarbitone sodium. Carbonised microspheres (40,000-60,000), 15 micrometer +/- 5 micrometer in diameter and labelled with 85Sr (3M Company) were injected into the cannulated right atrium. After spontaneous breathing of room air the birds were killed and the radioactivity measured in the spleen, kidneys, brain, lungs and extrapulmonary primary bronchi. Small pieces of lung tissue were removed from the beginning (costal region), middle (costovertebral region), and the end (vertebral region) of the paleopulmonic parabronchi, in the direction of air flow. Microspheres found in samples of parabronchial tissue indicated the relative perfusion rates of the three regions. Thermal panting was induced in six domestic fowl and six pigeons, followed by injection of microspheres. No arteriovenous anastomoses were found to exist across the pulmonary bed in any of the species examined at rest or in the panting domestic fowl and pigeons. The extrapulmonary primary bronchus was found to be well perfused from the pulmonary artery in the domestic fowl and to a lesser extent in the other species. The perfusion of the parabronchi in the domestic fowl and pigeons at rest decreased in the direction of ventilatory gas flow. This blood flow gradient was significantly increased during thermal panting in the domestic fowl, but not in the pigeon.

An extended course in general practice sponsored by regional advisers and university departments of general practice in Scotland, consisting of six sessions lasting two to four days interspersed with group discussion meetings and spread over a period of 18 months, is described and evaluated. Participants developed skills in teaching, confidence in group learning and insight into their abilities as teachers and organizers of training in general practice.

A survey was carried out of the career experience of the doctors who graduated from Scottish medical schools in 1962. Few of those in general practice in the UK had undergone the minimum period of vocational training now considered necessary for new entrants to practice. Of those in the hospital and specialist services, 53% were consultants. There was a tendency for early career decisions to be made, leading to an increasing number of doctors obtaining postgraduate training almost exclusively in one specialty. Many married women doctors were underemployed. A quarter of the doctors were living overseas, including those of the nonBritish nationals who had returned to their country of origin.

This article introduces the discipline of medical anthropology and presents concepts that may be useful for physical therapy clinicians. The terms culture and cultural orientations of the United States are defined, and examples of cultural conflict in patient care are given. I explain the differences between emic and etic viewpoints and analyze this distinction in relation to health care in the United States and especially the separation of the concept of disease and illness. Anthropological tools are presented for restructuring encounters between clinicians and patients to make clinicians more culturally sensitive.