# Guide LF N TH MSSPP - Epsd 1

This one can be written as The mass of the field defined as the second derivative of the potential is This happens for. Additional dependence can show up through the gauge coupling functions D-terms. B Babu Spring Physics Seminar Wichita. Memorial Conference in Honor of Julius Wess.

Danielsson 24 th Nordic Conference. Growing neutrinos and cosmological selection. Quintessence C. Wetterich A.

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Hebecker, M. Doran, M. Lilley, J. Schwindt, C. Thommes, R. Shaw Portsmouth,. Most importantly, the diagnosis of GERD has been increasing at an alarming rate, more than tripling between and Altman et al. This rise has become a substantial burden on our population, which is likely to continue to worsen. The susceptibility of the human aerodigestive tract to LPR has recently been described within an evolutionary perspective in studies from our laboratory Laitman and Reidenberg, ; Laitman and Reidenberg, By comparing the anatomical position of the adult human larynx to human children and other mammals, the studies demonstrated that the adult human larynx's caudal shift from an intranarial position makes it unsuited to accommodate reflux to the region.

The descent of the larynx during development unifies what were two largely separate pathways, namely, the respiratory tract and the digestive tract. This altered positional relationship allows the respiratory tract to be exposed to reflux reaching this level of the throat. Furthermore, the relatively unprotected posterior larynx of the adult human is inadequate to shield the laryngeal vestibule from exposure to reflux Laitman and Reidenberg, In recent years, major efforts have been made to gain a better understanding of the anatomical, physiological, neurobiological, and cellular mechanisms that break down to allow reflux to reach the laryngopharynx and, once there, cause disease.

There are four antireflux barriers that normally exist to protect against LPR: the gastroesophageal junction, esophageal motor function and acid clearance, the upper esophageal sphincter, and pharyngeal and laryngeal mucosal resistance. The goal of this review is to present the current understanding of how these antireflux barriers must sequentially fail in order for LPR to occur. The first antireflux barrier is the gastroesophageal junction Fig. This barrier consists of a complex sphincter with smooth muscle elements of the lower esophageal sphincter LES and skeletal muscle of the crural diaphragm, which combine to maintain pressure at this junction.

The LES is a physiological sphincter defined as the 3—4 cm area of tonically contracted smooth muscle at the distal end of the esophagus. The sphincter relaxes after swallowing to allow passage of ingested materials into the stomach. Anatomically, the zone corresponds to the most distal portion of the esophagus and is 2—3 times thicker than the proximal esophageal wall. The diaphragmatic crural fibers, whose action augments the LES at the distal esophagus, are attached to the LES by the phrenoesophageal ligament.

The gastroesophageal junction indicating a the normal anatomy of this region with the functional tonically contracted region of the LES indicated with a bracket and b anatomic disruption of the junction as occurs with a sliding hiatal hernia. Physiologic phenomena such as hypotension of the lower esophageal sphincter and transient lower esophageal sphincter relaxations result in the passage of reflux into the esophagus. When they occur in conjunction with a hiatal hernia, this reflux is accentuated.

Investigation of LES function frequently uses manometry, a clinical test where a transducer measures intraluminal pressures created by muscular tone. Physiologically, reflux into the esophagus can occur multiple times a day without causing disease; it is an established pattern of reflux that determines the manifestations of disease.

GERD patients usually have numerous and prolonged periods of reflux exposure, usually in the recumbent position. LPR patients tend to have more infrequent upright reflux of short duration that reaches the laryngopharynx without causing esophageal damage Koufman et al. It is with these patterns in mind that mechanisms of reflux across the gastroesophageal junction should be considered. The first theory, TLESR, involves a physiologic phenomenon in which there is a sudden drop in pressure at the LES, which is accompanied by crural diaphragmatic inhibition and not preceded by swallowing.

TLESRs typically last longer than relaxations after swallowing and are primarily triggered by gastric fundus distention after a meal. The vagus nerve serves as both the afferent and efferent arc of the mechanism, resulting in release of nitric oxide and vasoactive intestinal peptide to mediate muscle relaxation Hornby and Abrahams, Abnormal levels of reflux are thought to be attributed to either an increased frequency of TLESRs or an increased frequency of acid reflux during a TLESR, since not all transient relaxations are accompanied by reflux.

Patients with GERD had an increased rate of TLESRs compared to the control group with all subjects lying on their right side, whereas no difference in frequency was noted when subjects sat upright Sifrim and Holloway, Since patients with LPR frequently reflux while upright, it is unlikely that an increased frequency of TLESRs would explain the abnormal reflux in these patients.

Hypotension of the LES is the second theory of how dysfunction of the gastroesophageal junction promotes reflux. LES function in LPR patients was measured during reflux episodes to the proximal esophagus versus the distal esophagus. Since reflux to the proximal esophagus is more likely to reach the laryngopharynx than reflux to the distal esophagus Shaker et al. Two studies measured basal LES pressures in patients with LPR and found them to have pressures comparable to the control group Shaker et al.

It is possible that due to the intermittent nature of the reflux associated with LPR, these studies failed to capture the LES response during a reflux event. Therefore, the role of LES hypotension is unclear, but its role in proximal reflux events likely makes it a cause of LPR. The third theory implicates a sliding i. A sliding hiatal hernia is an anatomical defect where the distal esophagus and the gastric cardia herniate upward through the esophageal hiatus of the diaphragm, thus shifting the LES into the thoracic cavity.

It is the most common type of hiatal hernia and is usually an acquired condition that is often associated with no sequelae. The hernia is associated with widening of the muscular hiatal tunnel and laxity of the normally elastic phrenoesophageal ligament Kahrilas, and, most importantly, results in uncoupling the combined effect of the diaphragmatic crural fibers and LES in maintaining basal tone at the gastroesophageal junction.

Hypotension of the LES in patients with a hiatal hernia is thought to occur for two reasons. First, as mentioned previously, the pressure imparted by crural fibers is no longer imparted over the LES. Therefore, minimal tone in the esophagus would be sufficient to prevent reflux. However, herniation into the thoracic cavity exposes the entire esophagus to negative pressures, which counters the positive pressure created by the LES. Therefore, any patient with a hiatal hernia would be more likely to reflux into the esophagus during TLESRs or hypotension of the LES than if the gastroesophageal sphincter was in its normal anatomic position.

More studies that measure LES function when reflux reaches the laryngopharynx would be useful to better characterize the precise gastroesophageal junction deficiency encountered in LPR. The concurrent presence of these two phenomena with a hiatal hernia exacerbates the disease. The second antireflux barrier is the normal motor function of the esophagus Fig.

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Boluses of food and water are pushed by a strong coordinated peristaltic wave from the pharyngoesophageal junction down past the gastroesophageal junction and into the stomach. Peristaltic waves are either primary i. These peristaltic sequences are important in clearing any reflux back into the stomach.

Reflux remaining in the esophagus is then neutralized by swallowed saliva delivered during primary peristalsis. Any disturbance in normal esophageal motility increases the likelihood that reflux could travel the full length of the esophagus into the laryngopharynx.

This study looked exclusively at primary peristalsis and found that the most common motility disorder was ineffective esophageal motility, an abnormality characterized by occasional low contraction strength, contraction that fails to be transmitted along the whole length of the esophagus, and incomplete LES relaxation. This mechanism clears reflux back to the stomach and delivers saliva to neutralize any remaining reflux. This disorder is characterized by occasional low contraction strength e and f , loss of contraction as the peristaltic wave is transmitted along the length of the esophagus e—g , and incomplete LES relaxation h , which, in combination, increases the chance that reflux reaches laryngopharynx once in the esophagus, as occurs in LPR.

Secondary peristalsis is normal in LPR. The finding of abnormal esophageal motor function was confirmed by another study, which compared esophageal acid clearance time in patients with LPR and the control group Postma et al. Esophageal acid clearance time is the amount of time necessary to return the esophagus to a neutral pH following an acidic reflux event. This time is affected by both overall esophageal motor function and salivary neutralization. Since the authors of the study assume that the latter component is constant among subjects, esophageal acid clearance time becomes a good measure of esophageal motor function.

The study found that patients with LPR had significantly longer clearance times than the control group, but the times were not as long as in patients with GERD. Secondary esophageal peristalsis has also been examined in patients with LPR Ulualp et al. Stimulation of the esophagus via abrupt injections of air volumes invokes a peristaltic wave.

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The threshold to trigger the peristalsis was comparable between LPR patients and the control group. Additionally, the parameters of the pressure wave amplitude, duration, and velocity were similar between the two groups as well. Thus, abnormalities in primary peristalsis but not secondary peristalsis characterize the esophageal dysmotility found in patients with LPR.

These results are not surprising given that the pharyngeal swallow and the resulting primary peristaltic wave are considered to be the predominant mechanism in returning reflux back to the stomach Bremner et al. This conclusion reinforces the fact that GERD is characterized by excessive exposure of reflux to the esophagus, whereas the sequelae of this excessive contact is usually lacking in LPR patients. Reflux in LPR must travel rapidly through the esophagus on the way to the laryngopharynx, where the problems of the disease manifest.

The third antireflux barrier is the upper esophageal sphincter UES; Fig. Like the LES, it relaxes to allow the passage of food or liquid boluses during swallowing. The UES is made up of the most distal fibers of the inferior pharyngeal constrictor i. The cricopharyngeus muscle makes the largest contribution to pressure at the UES in all physiologic states Lang and Shaker, The pressure of the UES demonstrates a wide range of variation. For example, pressures decrease significantly during sleep, periods of calmness, and even expiration Kahrilas et al. Pressures have also been shown to be lower in the elderly Fulp et al.

The larynx with the functional tonically contracted region of the UES indicated with a bracket. Abnormal response of reflexes that prevent the passage of reflux to the laryngopharynx is thought to contribute to laryngopharyngeal reflux. The only thing that irks me is that the storylines for the gay relationship and the residents affair etc dont seem to be relevant to the story and the main story would still continue without these characters. On episode 6 and Im waiting for it to come together some how. Despite that its worth watching to see Renee in a different roll than weve seen her play and she plays powerful tortured, lonely, cruel and intriguing very well indeed.

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• INTRODUCTION!
• High-precision predictions for the MSSM Higgs sector at ${{\mathcal{O}}}(\alpha_b\alpha_s)$.
• 1 Dark Energy & MSSM Jérôme Martin Institut d’Astrophysique de Paris (IAP)!
• Anatomy of reflux: A growing health problem affecting structures of the head and neck?

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