Discussion. The pathogenesis of SOC in women has been subject to extensive research and controversy. The traditional view holds that ovarian cancer arises from Mu¨ llerian epithelium on the ovarian surface or from intracortical inclusion cysts; however, evidence at the clinical, histopathological, or DNA level is lacking to prove this concept. Here, we provide support for our previously described hypothesis10 that en- dometrial EIC is a likely precursor lesion for SOC based on immunohistochemical staining patterns, TP53 mutation, and DNA aneuploidy analyses. Our immunohistochemistry data provide first evidence for a possible relation between EIC and coinciding SOC. We found that immunostainings for 4 proteins (p53, MIB-1, ER, and PR) revealed almost identical staining patterns and similar intensities for each pair of EIC and corresponding SOC. These findings are concordant with recently published data in which similar expression profiles were shown be- tween EIC and extrauterine deposits in the ovaries, fallopian tube, omentum, or peritoneum.22,26,27 Our histopathologic examination and immunohistochemical data alone cannot unequivocally distinguish between a monoclonal or multi- centric origin. Endometrial intraepithelial carcinoma in the uterine cavity, although without myometrial invasion, can be associated with extensive extrauterine carcinomatosis.26,28Y30 Several theories have been proposed to explain the relation- ship between intrauterine disease and extrauterine disease, including early lymphatic spread and synchronous primary tumors (multicentricity). Endometrial intraepithelial carci- noma may present with focal lymphovascular invasion and lymphovascular metastasis may explain their extrauterine spread in some cases. However, only 3 of the 9 cases of EIC in this study with concordant SOC showed lymphovascular invasion. Importantly, EIC can present with extensive peri- toneal metastases. Shedding of the (pre)malignant tumor cells into the uterine cavity after which the cells are transported through the fallopian tube lumen onto the ovaries and other pelvic peritoneal surfaces is the most likely mechanism. This is also substantiated by infrequent findings of so-called in- transit deposits of serous carcinoma cells in the fallopian tube. Alterations in cell surface adhesion molecule expres- sion, including E-cadherin and A-catenin, is associated with the loosely cohesive nature of these (pre)malignant cells resulting in implantation at distant sites.31Y33 The m...
Discussion. Staff has reviewed the proposal relative to all relevant policies and advise that it is reasonably consistent with the intent of the MPS. Attachment B provides an evaluation of the proposed development agreement in relation to the relevant MPS policies.
Discussion. OSAS is a serious public health problem. Its high prevalence (estimated to be 2% in women and 4% in men10,11), combined with the increased recognition it has received in recent decades, has led to a spectacular rise in the demand for studies of OSAS.12 Xxxxxxxx-Xxxxxx,12 for example, recently indicated that OSAS has now become the most common reason for referral to a respiratory medicine specialist in Spain. In view of the high prevalence of the disease, the increased public demand for studies in patients with suspected OSAS, and the limited access to diagnosis and treatment,13 more efficient diagnostic and care measures are required. Portable monitors are a useful diagnostic alternative to polysomnography studies, which are both costly and offered only by a reduced number of sleep clinics. Type-4 monitors, such as those based on single-channel airflow and pulse oximetry, have only been indicated for screening purposes to date.1 The growing tendency to use simplified monitoring devices is not limited to developing countries, however, given that an increasing number of developed countries are also focusing their efforts on finding a way to meet the needs of a growing number of patients at a reduced cost.2,14 It is therefore necessary to investigate the diagnostic yield of each and every one of the portable monitors on the market and to analyze the variables that could possibly influence their performance. High altitude, such as that of Mexico City, is one variable that, at least theoretically, could affect the diagnostic yield of pulse oximetry systems. We did not find this to be the case, however, when we compared oxygen desaturation values obtained by automatic measurement with AHI values obtained by polysomnography. In the circumstances described, the DI provided by the Xxxxxxx Sleep Recorder is a reliable indicator of AHI in Mexico City, a finding which coincides with those for other altitudes.5 Further studies involving a greater number of patients, however, are necessary to determine whether the high degree of agreement we observed is maintained in patients grouped by disease severity. Our findings revealed that the intraclass correlation coefficient decreased in patients with an AHI of less than 35; this implies that the diagnostic yield of pulse oximetry might vary in different groups of patients TABLE 2 Diagnostic Yield for Desaturation Index (DI) Cutoff Values Compared to Apnea–Hypopnea (AHI) Cutoff Values (Reference Values) Obtained by Polysomnog...
Discussion. In this study, we demonstrated substantial variability among experienced operators when deciding, on morphologic fea- tures alone, whether a series of aneurysms should be retreated and how. This finding is important for several reasons. First, it suggests that patient management following aneurysm recur- rence may vary widely among operators and centers. Second, these findings suggest that retreatment may not be an ideal outcome in a clinical trial, given wide interobserver variability. Third, it sheds light on a previously neglected aspect of patient care—that is, whom should we retreat and why? The underlying reasons behind the wide variation among our readers remain unknown but likely are multifactorial. Is- sues such as ease of retreatment probably impacted individual ratings—that is, rounded narrow-necked recurrences, irre- spective of size, might have prompted some reviewers to rec- ommend treatment. Difficult wide-necked cases might have prompted those who favor stents to recommend retreatment. This tendency is shown by the fact that in cases in which read- ers were uncertain about retreatment, surgery was recom- mended, while in cases with high degrees of certainty, readers were amenable to coil embolization without the need for a stent. In our study, roughly two-thirds of cases showed differ- ences of ≥2 points. A 2-point difference indicates a difference of “not sure” to “definitely treat” or “definitely do not treat”, or a difference of “probably treat” to “probably not treat.” Thus, even a 2-point difference might lead to differences in patient management. Thirty-seven percent of cases varied by 3 points. A 3-point variation indicates a difference between “definitely treat” to “probably not treat” or vice versa, again indicating substantial differences in patient management. One might theorize that treating physicians may be more likely to recommend retreatment for ruptured recurrent an- eurysms over unruptured recurrences in certain cases. To pre- vent this possible bias in the current study, we told the review- ers to assume that all patients were 50-year-old women who had XXXx from the index aneurysm and who had made full clinical recoveries, and that their follow-up imaging was per- formed at their 6-month return visit. This information was included to prevent retreatment bias based on rupture status, age, and recovery status; however, these likely play a strong role in a provider’s decision about recurrent aneurysm retreat- ment. More rese...
Discussion. The Parties mutually desire that friendly collaboration will continue between them. Accordingly, they will try, and they will cause their respective Group members to try, to resolve in an amicable manner all disagreements and misunderstandings connected with their respective rights and obligations under this Agreement, including any amendments hereto. In furtherance thereof, in the event of any dispute or disagreement (a “Dispute”) between any member of the Remainco Group and any member of the Spinco Group or RMT Partner as to the interpretation of any provision of this Agreement or the performance of obligations hereunder, the Tax departments of the Parties shall negotiate in good faith to resolve the Dispute.
Discussion. In the present population−based study, we provide insights into the daily practice and postoperative clinical course of patients that suffered from AL after colonic resection for primary colon cancer. We found an AL rate of 4.8%, ranging from 4.0% for right hemicolectomy to 15.4% for subtotal colectomy. AL was mostly managed with surgical reintervention (84.3%) and stoma construction (79.5%), but significant differences in reoperation and stoma rates were found for the different index colectomies. Also, the median time to reoperation differed significantly. Mortality rates of about 15% after reoperation were observed for index transversectomy and right hemicolectomy, and this was 6% for index sigmoid resection and subtotal colectomy. In addition, it was found that reoperations for AL after colectomy are accompanied by a substantial ICU admission rate and prolonged stay in hospital rate, which varies significantly among the different surgical procedures. Transversectomy patients demonstrated the most severe complicated course (e.g., higher ICU admission rate and mortality rate) but also are more often treated non−surgically compared to other colectomies. Right hemicolectomy patients suffering from AL were less commonly managed with reoperation and stoma creation than other colectomy types but showed a substantial mortality rate. After reoperation, the mortality rate was significantly higher for these patients when they received a stoma during reoperation, which might be related to the abdominal contamination. Compared to rectal cancer resection, construction of an anastomosis in colonic resection might be technically less demanding, and AL rates are generally lower. However, when AL occurs after segmental colectomy, it can easily spread throughout the peritoneal cavity, causing generalized peritonitis and rapidly developing sepsis.2,14 This might be the reason for the overall high mortality rates following reoperation, as observed in the present study. Interestingly, these mortality rates were more than twice as high after initial right−sided resections compared to sigmoid resection and subtotal colectomy. Xxxxxx et al. and Xxxxxx et al. found a decreased risk of AL after a right hemicolectomy, but with contrasting results regarding the AL-related mortality.2,17 Similar to our study, it was demonstrated that a subtotal colectomy has the highest risk of AL compared to all other types of colectomy, up to 23%.2,7,20 Surprisingly, mortality after reoperation fo...
Discussion. Treatment strategies for FAI syndrome have included conserva- tive care, rehabilitation and surgery. The panel agreed that each of these may have a role in different patients, but that there is little evidence to compare their effectiveness. Figure 1 is a sug- gested pathway for the management of FAI syndrome. There is currently no high-level evidence to support the choice of a definitive treatment for FAI syndrome.22 23 For any one patient, the panel agreed that it is appropriate to consider the different treatment options. This is best done in a shared decision-making process, supporting the individual patient to make an informed preference decision on the best treatment option for them.61 62 We agreed that those treating FAI syn- drome, particularly in secondary and tertiary care, should be part of a multidisciplinary group with knowledge of, and access to, all the treatment options. Conservative care of patients with FAI syndrome is poorly described but could include patient education, activity and lifestyle modification, oral analgesia including non-steroidal anti-inflammatory drugs, intra-articular steroid injection and watchful waiting.23 There are no reports of what effect such an approach, in isolation, has on the symptoms of FAI syndrome. Similar conservative strategies are recommended in other mus- culoskeletal disorders such as hip osteoarthritis.63 64 Physiotherapist-led rehabilitation aims to reduce patients’ symp- toms by improving hip stability, neuromuscular control and move- ment patterns.23 The treatment targets for rehabilitation are wide-ranging and include improving sagittal and frontal plane hip range of motion, hip muscle strengthening and lumbopelvic dissoci- ation.14 47 48 65 However, details of what should be incorporated in such a programme has not been well tested and it would appear that different physiotherapists are delivering different treatments.23
Discussion. A physical demands analysis was performed on UK Fire & Rescue Service operational firefighters using tasks representing accepted practice of necessary occupational tasks at a pre-defined minimum acceptable pace. Oxygen uptake for the five tasks ranged between 29-47 ml.kg-1.min-1 and between 64-92% of heart rate reserve. The hose run task elicited the highest steady state metabolic demand, and the wild-land fire task the lowest. All tasks were agreed to be authentic and accurate representations of occupational duties by over 90% of study participants, with the exception of the wild-land fire task (84%). During representative firefighting tasks lasting a total of five minutes, cardiovascular strain tends to rise between 85-100% of maximum (Xxxxxxx & Xxxxxx 1983). In 20 United States firefighters, Xxxxxxxx et al. (1990), observed seven successive firefighting tasks which elicited an average metabolic demand of 30.5 ml.kg-1.min-1, which represented 76% of the average VO2 max (39.9 ml.kg-1.min-1). However, during stair climb and casualty evacuation tasks Xxxxxxxx & Xxxxxx (1992) and xxx Xxxxxxxx, Xxxxxxxxx & Xxxxx (2006) in Canadian and Norwegian firefighters, respectively, measured substantially higher values (44 ml.kg-1.min-1), similar to those in the present study. The above studies involved entirely self-paced tasks. Xxxxxxxx et al. (1990) observed that fitter individuals would tend to perform tasks faster than less fit individuals, suggesting that in emergency situations, less fit individuals would compensate by completing the tasks slower. This further highlights the importance of a minimum acceptable pace as a means of measuring physical demand. In a study where minimum acceptable pace has been employed, the average physical demand of a sample of UK shipboard Naval firefighters over five tasks was 36.2 (range 23-43) ml.kg-1.min-1 representing between 44 and 82% of the average participant VO2 max (Xxxxxx et al. 2001). Although these tasks are paced and designed to elicit a valid steady state of physical demand, it is evident that wide variation exists in the occupational roles and subsequent tasks performed in different national services. As such, the specificity and experimental control implemented within the present study produce the most accurate description of the physical fitness required to safely and effectively complete the role of an operational UK firefighter. Physical demands analyses can be used to produce a physical fitness standard for safe ...
Discussion. In this study we found higher levels of IgG1 anti-TT antibodies after vaccination of the rural children compared to the semi-urban children, although IgG1 avidity was not different amongst the groups. Further, the observation that IgG3 anti-TT was elevated in the rural subjects was unexpected, as IgG3 is mainly induced upon primary vaccinations with protein antigens like TT [181]. High levels of IgG3 were present in children that were found to have plasmodia infections during the study, however, this could not account for the difference between the semi-urban and the rural cohorts. Whether the observations in our study could be ascribed to helminth infections, could not be determined, as all rural children were infected with at least one helminth species. However, when comparing helminth infected children from the semi-urban area separately to non-infected semi-urban children or the rural cohort, these children showed antibody levels with a geometric mean more close to the semi-urban non-infected children than to the rural children. However, these differences did not reach significance, indicating that helminth infections might contribute to the difference, but are not the only factor. This is in accordance with other studies that have either found no effect of filarial infections on total IgG and IgG1 anti-TT antibodies following TT vaccination [34, 37], although in an other study a higher total IgG response in subjects free of onchocerciasis infections was found [36]. However, in these studies, antibody levels were analysed as fold increase above baseline pre-vaccination levels. When we transformed our data accordingly, no differences between the groups were found in any of the IgG subclasses. It remains to be discussed whether the actual levels or the percent increase represent the best indicator of the response upon immunization. We preferred to compare the actual levels, since higher levels before vaccination, which could be due to natural exposure or more effective prior vaccinations, would lead to reduced values in terms of fold increases, whereas the absolute levels of antibodies, which are thought to be an indication of protection, could be similar. In general, other studies have investigated the difference between helminth infected and non-infected subjects. However, here we show that besides the helminth infections status, other factors are involved in the outcome of Cellular and humoral responses to tetanus vaccination in Gabonese children vacc...
Discussion. For minor offenses by an employee, management has a responsibility to discuss such matters with the employee. Discussions of this type shall be held in private between the employee and the supervisor. Such discussions are not considered discipline and are not grievable. Following such discussions, there is no prohibition against the supervisor and/or the employee making a personal notation of the date and subject matter for their own personal record(s). However, no notation or other information pertaining to such discussion shall be included in the employee’s personnel folder. While such discussions may not be cited as an element of prior adverse record in any subsequent disciplinary action against an employee, they may be, where relevant and timely, relied upon to establish that employees have been made aware of their obligations and responsibilities.