15 All these developments resulted from tight collaborations between physicians and engineers with industrial and financial support around them. Many new companies were founded and later merged into larger companies. It was a bubbling and vibrant community with tight collaborations between academia, clinical institutes, and industry. After FDA approval of the Palmaz–Schatz stent, stent penetration into the market was unprecedented. Within 4 years (1994–1998), stent usage climbed from 0% to 80% of PCIs. Abrupt coronary occlusion was minimized to a reasonable percentage, and restenosis

was reduced (but not eliminated). In a recent interesting paper, Xu et al.16 studied the innovative Inhibitors,research,lifescience,medical process in coronary stent development. Their results showed the central role of physician-innovators and their small private

companies in helping create this field. Larger public companies made their contributions later in the product development time-line. The Inhibitors,research,lifescience,medical authors suggest implementing new policies in academic and clinical institutions, Inhibitors,research,lifescience,medical aimed at encouraging transformative medical device development through translational research at the early stages of technology development. THE TRIANGLE OF COLLABORATIONS BETWEEN INDUSTRY, ACADEMIA, AND PRACTICING PHYSICIANS The disrupting technology of balloon angioplasty and stenting has driven numerous competitive attempts to develop stents from different metals such as tantalum, titanium, self-expanding nitinol alloy, and even gold coated with diamond dust.17 It has been a virtual parade of large and small industry-driven initiatives, attempting to improve this disruptive technology in small additive steps. Various manufacturing

techniques Inhibitors,research,lifescience,medical involved major industries that specialized in stent-related technologies. Refining stent-balloon delivery performance and dealing with profile, flexibility, and tractability were huge challenges for this dynamic engineering world. Surface coating with inherent materials such as carbon, stable polymers, and even conjugated heparin molecules was attempted Inhibitors,research,lifescience,medical in order to achieve better tissue compatibility. However, restenosis was not reduced until the industry, sparked by combining pharmacology and biomaterials, 4-Aminobutyrate aminotransferase developed the first drug-eluting stent. The first drug-eluting stent was a standard metal stent, coated with a layer of durable CP-868596 solubility dmso polymer containing sirolimus, an anti-proliferative drug, covered by another layer of polymer to control the release of the drug over 8 weeks.18 This represented a huge disruptive technology—an optimally matched combination of a device and a drug. It was also a victory for the tight collaboration between the engineers and scientists, appropriately applied to patients by clinicians. This classic triangle of interaction between industry, academia, and practicing physicians was once again proven successful.

To the editor, Dr. Takatori and colleagues deserve praise for meticulously studying the extent and severity of upper gastrointestinal (GI) complications in 91 inoperable pancreatic cancer patients treated on a prospective clinical trial with proton-based radiotherapy and concomitant gemcitabine chemotherapy (GPT) (1). The significant complications observed in this series (49.4% rate of gastric/duodenal ulceration), however, starkly contrast the Inhibitors,research,lifescience,medical favorable IKK Inhibitor VII chemical structure toxicity profile we observed in our series of pancreatic cancer patients treated with proton therapy and concomitant capecitabine chemotherapy (2). In our series, we observed no grade 3 toxicities in patients

receiving proton doses ranging from 50.40 to 59.40 Cobalt Gray Equivalent (CGE) at 1.8 CGE per daily fraction with daily oral capecitabine Inhibitors,research,lifescience,medical (1,000 mg twice daily). The median weight loss during treatment was only 1.3 kg (1.75% of body weight). Additionally, when radiotherapy plans avoided the use of anterior or left lateral

fields—reducing small bowel and gastric exposure—grade 2 GI toxicity was eliminated and median weight loss was only 0.5 kg. Possible explanations for the disparity of outcomes between these two series might include: (I) aggressive radiotherapy doses [67.5 Gray equivalent (GyE)] and high dose per fraction (2.7 GyE) delivered in the GPT series; (II) concomitant delivery of full-dose gemcitabine Inhibitors,research,lifescience,medical (800 mg/m2 on days 1, 8, and 15), well-recognized as a potent radiosensitizing agent; and (III) radiotherapy fields expanded to include regional lymph nodes in addition to the primary tumor. Although details of the radiotherapy Inhibitors,research,lifescience,medical plans were not included in the GPT publication, it is possible that some of the toxicity might have been mitigated if anterior and left lateral fields had Inhibitors,research,lifescience,medical been avoided or the dose delivered through such fields was minimized. While the current study is well-designed and well-reported, it would be wrong to conclude that proton therapy for patients with pancreatic cancer is associated with a high rate of gastrointestinal toxicity. Indeed, we have every reason to believe,

based on its superior dosimetry (3), that proton therapy offers significant improvements in the therapeutic index compared to X-ray-based therapies such as intensity-modulated Calpain radiotherapy. Our clinical experience helps confirm the hypothesis, based on this dosimetry, that proton therapy reduces GI toxicity and may allow for treatment intensification—although perhaps not to the same degree as the intensification offered on the GPT protocol. We appreciate you taking the time to consider our letter and look forward to hearing from you in the future. Acknowledgements Disclosure: The authors declare no conflict of interest.
While pancreatic cancer remains an almost uniformly fatal diagnosis, data suggest that advances in treatment have resulted in modest gains in overall survival for local (1,2) and metastatic (2,3) disease.

Secondary outcomes 1. Mean xerostomia inventory score [23]; 2. Oral health related quality of life; 3. Adverse events (according to NCI Common Terminology for Adverse Events [24]); 4. Dysphagia (difficulty NSC683864 research buy swallowing); 5. Dysgeusia (distortion of taste); 6. Global impression

of change. The trial will be reported according to the Consort statement [25], and analysis will be on an intention-to-treat basis. Patient assessment 1. Outcome Measures The schedule of assessments is presented in Table 1. The outcome measures assess different aspects of the trial as follows: Table 1 Schedule of Inhibitors,research,lifescience,medical assessments (a) Response to pilocarpine: (i) Numerical rating scale (NRS) for xerostomia. The NRS consists of a range of numbers, with the smaller numbers indicating less dry mouth. An 11-point NRS rates symptom intensity corresponding to an integer number between 0 and 10. People rate their dry mouth by marking a number Inhibitors,research,lifescience,medical on a paper that lists the numbers horizontally in ascending order. The NRS has well-established psychometric properties; being valid, reliable, and sensitive to change. It is nonintrusive, easy to administer and score, and suitable for repeated use [26]. Although no studies were found on the psychometric properties of NRS in xerostomia, NRS are commonly used in studies of this condition. Severity of xerostomia will be measured using Inhibitors,research,lifescience,medical a 0-10 cm NRS ranging

from 0=no dry mouth to 10=worst possible dry mouth. At each assessment point, patients will be asked to score their current, worst, best and average dry mouth score over the preceding 24 hours. Dysphagia and dysgeusia (a distortion of Inhibitors,research,lifescience,medical the sense of taste) scores will also be recorded

in a daily diary using a 0-10mm NRS. (i) The xerostomia inventory (XI) [23], a valid and reliable scale for measuring xerostomia symptoms, will also be used as a secondary measure. (a) Performance status: Australian Karnofsky Performance Scale (AKPS) [27]. This scale assesses functional performance and is a validated modification of the gold-standard Inhibitors,research,lifescience,medical Karnofsky Performance Scale, altered to apply to both community and hospital patients. It has high test-retest reliability, high predictability of survival time, and sensitivity to change towards the end of life. (a) Presence of side-effects: Any toxicity will be rated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE) v3.0 [24]. The trial will be overseen MRIP by an independent data safety monitoring committee. (a) Quality of life (QOL) indicators: (i) EORTC-QLQC15-PAL core items [28], is a general cancer QOL questionnaire suited to a palliative sample as it yields data on overall QOL, physical, emotional and social functioning and other symptoms, has been extensively validated, has reference data available and uses standardised scoring procedures, with evidence concerning interpretation of scores.

5 Following IPT, MDD participants had metabolic changes in the direction of normalization in these brain regions. Symptomatic improvement was accompanied by significant increases in the left temporal lobe

and anterior insula, and significant decreases in the right middle frontal gyrus (including both the ventrolateral PFC [VLPFC] and the dorsolateral PFC [DLPFC]), right dorsal caudate, and left middle anterior cingulate cortex (ACC). Moreover, improvement in cognitive function positively correlated with changes in DLPFC metabolism, whereas Inhibitors,research,lifescience,medical reductions of ventral and dorsal PFC metabolism were associated with decreases in anxiety/somatization and psychomotor retardation symptoms. Normal control volunteers had no significant changes in these brain areas. Other neuroimaging studies have examined the effects of cognitive behavioral therapy (CBT) in people with MDD. CBT seeks to train patients to identify and change negative beliefs and negative interpretations related to the past, present, and future.2 In one of these investigations, Goldapple Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical et al6 used 18FDG-PET to measure the brain changes induced by CBT in 17 unmedicated Flt3 inhibitors clinical trials individuals with MDD. Participants were scanned before

and after a 15- to 20-session CBT treatment. During treatment, participants learned a number of behavioral and cognitive strategies aiming to combat dysphoric mood and diminish automatic reactivity to negative thoughts and attitudes. Specifically they were taught cognitive monitoring to Inhibitors,research,lifescience,medical dismantle ostensibly complex chains of thinking and feeling into separate elements; they were also requested to increase the frequency of pleasant events in their lives, to record their thinking using thought records, and to test their interpretations and beliefs between sessions. Significant clinical improvement was noted in the 14 study completers. This improvement was accompanied by increases in the parahippocampal gyrus and dorsal Inhibitors,research,lifescience,medical ACC (Brodmann area [BA] 24), and decreases in dorsal (BA 9 and 46), ventral (BA 47 and 11), and medial (BA 9, 10 and 11) PFC. In another 18FDG-PET investigation, Kennedy and coworkers7

scanned 12 individuals with MDD before and after 16 weeks of treatment with CBT. Response to CBT (n=7) was associated with increased glucose metabolism Montelukast Sodium in the right inferior occipital cortex, as well as reduced glucose metabolism in the lateral orbitofrontal cortex (BA 11 and 47) and left dorsomedial PFC (BA 8). Symptom reduction is one of the main objectives of psychotherapy. Therefore, the identification of the neural correlates of symptom reduction is a primary aim of the neuroimaging studies of psychotherapy. In this context, symptom provocation can allow researchers to compare brain responses to trigger scenarios or stimuli before and after treatment, and thus assess the impact of psychotherapy on brain activity.

PROXIMAL ANASTOMOSIS DEVICE Manipulation of the ascending aorta during cardiac surgery is one of the leading causes of embolic events and postoperative stroke; atheromatous disease of the ascending aorta is more prevalent in the elderly population.5,6 Evolving technologies of proximal anastomosis devices tested the ability to serve the goal of surgeons to minimize manipulation of the ascending aorta during surgical myocardial revascularization, as emboli generated

during cardiac surgery have been associated with aortic clamping Inhibitors,research,lifescience,medical and manipulation. At first, proximal anastomotic devices were thought to be less traumatic by eliminating partial clamping, potentially resulting in fewer adverse outcomes; however, their use has ceased due to

the accumulation of substantial discouraging PDE inhibitor evidence. Inhibitors,research,lifescience,medical In 2004, Martens et al. compared the amount of debris released using intra-aortic filtration and the clinical outcomes between conventionally hand-sewn and automated Inhibitors,research,lifescience,medical proximal anastomoses.5 This comparison was carried out through the investigation of 77 patients undergoing primary CABG with cardiopulmonary bypass in a prospective randomized study. Patients were assigned to the anastomotic device Group I (Symmetry Aortic Connector, St. Jude Medical, Inc., St. Paul, MN, USA; n = 39) or the conventional hand-sewn anastomosis control Group II (n = 38). Proximal

anastomoses were performed before cardiopulmonary bypass in both groups. Intra-aortic Filter 1 (EMBOL-X, Edwards Lifesciences LLC, Irvine, CA, USA) was deployed prior to partial clamping Inhibitors,research,lifescience,medical or puncturing the aorta for device application and removed after the proximal anastomosis was completed. Prior to cross-clamp removal, a second filter was inserted (Filter 2). A core laboratory performed quantitative Inhibitors,research,lifescience,medical and histologic analyses of the debris captured. Martens et al. demonstrated that preoperative variables and risk factors were not significantly different between Groups I and II (European System for Cardiac Operative Risk Evaluation (EuroSCORE) 3.9 ± 2.6 versus 4.2 ± 2.5, respectively). Filter analyses showed no significant difference between Groups I and II in Filter 1 or 2 for either surface area of particles or total number of TCL particles. A decrease was observed between Filters 1 and 2 in both groups for surface area of particles (Group I: 18.5 ± 23.8 mm2 versus 10.7 ± 16.3 mm2, P = 0.017; Group II: 15.0 ± 15.4 mm2 versus 6.9 ± 6.5 mm2, P = 0.004), and for total number of particles in Group II (8.6 ± 3.7 versus 7.1 ± 2.4, P = 0.023). No significant differences were observed between Group I (device) and Group II (control) outcomes for myocardial infarction, neurocognitive deficit, stroke, length of stay, graft occlusion, or mortality.

105 Therefore, RLS and PLMD are distinct by definition, but may coexist. A recent study found that several polysomnographic features in RLS differ from those of PLMD,106 suggesting that different pathophysiological mechanisms may influence sleep in both conditions. RLS and PLMD are highly prevalent. RLS is found in 9% to 15% of adults107,108 and its prevalence increases with age. PLMS may occur in up to 6% of the general population109 and in 20% of patients aged 60 years or older.110 The unpleasant sensations experienced by patients with RLS Inhibitors,research,lifescience,medical often lead to noticeable loss of sleep, with the more severely affected patients sleeping no more than 4 to 5 h and experiencing deficits in daily functioning.

Patients also report problems with functioning in sedentary situations, particularly in physically constraining places, and also in the evening when the symptoms are usually exacerbated. As a result, patients may have problems accomplishing their jobs and participating in social and recreational activities.111 Symptoms, along with the impairment Inhibitors,research,lifescience,medical of sleep,

may cause distress Inhibitors,research,lifescience,medical and lead to psychiatric illness and decreased well-being. In the 19th century, Wittmaack described the cooccurrence of RLS with symptoms of depression and anxiety, and suggested the term “anxietas Mdm2 inhibitor tibiarum.”112 Although the first modern study attracting attention to psychiatric comorbidity, showing higher scores on depression and psychoasthenia in RLS patients, was performed 40 years ago,113 little progress has been made since then in attempts to explore this relationship. Despite their high prevalence in the general population, little information is available on the impact of PLMS or RLS on quality Inhibitors,research,lifescience,medical of life. In a recent American Academy of Sleep Medicine review, reference is made to the “striking omission” of quality of life research Inhibitors,research,lifescience,medical and psychological impact with respect to this disorder.114 In two drug trials utilizing a modified version

of the Hamburg Visual Analog Scales, improvements after dopaminergic treatment (first-line therapy for RLS) were noted in activities of daily living, mental function, fatigue, and depressive feelings.115,116 A more recent large survey suggested a substantial impact of RLS on quality of life equivalent to or worse than some other major chronic medical disorders.117 This impact was apparent on all of the SF-36 items, but the more pronounced during deficits occur for measures of vitality/energy and limitations of work and activities due to physical problems, suggesting a major decrease in the level of alertness and energetic engagement with daily function. The data also indicate that patients with RLS are likely to have problems with anxiety or depressed feelings. This is in accordance with other data suggesting that patients with RLS are likely to experience mental health problems.

Marjolin’s ulcer is classified into acute and chronic subgroups. Acute scar carcinoma, which is rarely seen, occurs sooner than one year after injury.7 Acute Marjolin’s ulcer is more often basal cell carcinoma and is associated with more superficial burn scars.5 The latency period is inversely proportional to the patient’s

age at the time of burn injury.1 The mean average period of chronic carcinoma development, more frequent type, is 35.5 years.7 We herein present an otherwise healthy 54-year-old Jewish man, who developed Marjolin’s ulcer only 6 weeks after his burn injury. The patient had superficial scald burn injuries, about 3% of the body surface area, on his right foot and right hand, which Inhibitors,research,lifescience,medical healed with conservative management after 3 weeks. Two weeks later, a 10-mm exophytic fragile nodule, which

bled with minor manipulation, was noted in the dorsal aspect of his right hand. The nodule was excised completely, the wound was closed Inhibitors,research,lifescience,medical primarily, and the tissue was sent for histopathologic evaluations. The histopathology of the lesion was well-differentiated squamous cell carcinoma (figures 1 and ​and2).2). Consequently, re-excision with a 10-mm margin was done, and full-thickness skin graft was performed. The confirmation of complete excision was done by Inhibitors,research,lifescience,medical the pathologist. Now 2 years on since the excision, the patient is systemically well, with no evidence of local recurrence. Figure 1 Ulceration with invasion of malignant keratinizing squamous cells through the dermis (H&E ×100). Figure 2 Nests of well-differentiated squamous cells, producing keratin

pearls (H&E ×100). Marjolin’s ulcer is a potentially aggressive malignant tumor, which has a typically long latency period. Although Inhibitors,research,lifescience,medical acute Marjolin’s ulcer (latent period less than one year) is very uncommon, Inhibitors,research,lifescience,medical we believe that the appearance of any nodules or ulceration on a healed burn area at any age or site and with any latent period should be excised and evaluated histologically. Conflict of Interest: None declared.
Inguinal bladder hernia is a rare clinical condition. Indeed, only 1-3% of all inguinal hernias are reported to involve the bladder.1 The incidence may reach 10% among obese men older than 50 years of age, however.2,3 Massive inguinoscrotal bladder hernia, also known as scrotal cystocele, is a Megestrol Acetate very rare condition.1 In this condition, one portion of the bladder or a diverticulum forms all or a part of the scrotal hernia. Even more uncommon is inguinal bladder hernia descending into the scrotum. Small bladder hernia is usually asymptomatic, whereas large scrotal bladder hernia presents with intermittent scrotal or inguinal bulging and lower urinary tract symptoms and occasionally patients complain of double voiding. Diagnosis is find more confirmed with cystography and ultrasonography. Surgical repair of hernia is the best choice for treatment.

130 Other chronobiological changes that have been identified

are phase-delay,131 decreased selleck inhibitor amplitude of variables,41 and possible changes in ultradian rhythms.132 Some facts cannot be interpreted either in favor or against the hypothesis of changes in chronobiology in mood disorders. For example, only a very small proportion of subjects became depressed during free-running experiments. Also, severe Inhibitors,research,lifescience,medical psychiatric manifestations during jet lag occur only very rarely. Finally, electroconvulsive therapy can have acute and immediate beneficial effects in melancholia, either by a release of endogenous compounds or by a form of resetting of cerebral or biological clocks activities. There are also arguments against a direct role of biological clocks in mood disorders. Inhibitors,research,lifescience,medical Seasonal affective disorder Seasonal affective disorder (SAD) is among disorders with a circannual period. This was recently described by Rosenthal and his collaborators.133 They defined it as a syndrome characterized by recurrent depression that occurs annually, generally at the same time each year, for several years. They Inhibitors,research,lifescience,medical described 29 patients, most of them presenting depression from early fall during all winter,

with hypersomnia, hyperphagia, and carbohydrate craving. The temperature pattern was normal during depression,134,135 or showed a decrease in amplitude.136 This mood disorder is considered to have a high prevalence, which somehow does not correspond to the impression of some psychiatrists, perhaps because they do not recognize SAD, or because Inhibitors,research,lifescience,medical SAD patients consult psychiatrists less than do other dépressives. The pathophysiology of SAD might involve a phase-delay of circadian rhythms.77 Light therapy is useful,137 as are selective serotonin reuptake inhibitors (SSRIs). Premenstrual syndromes The DSM-III-R label of late luteal phase dysphoric disorder was replaced by the actual

wording of premenstrual dysphoric disorder (PMDD) in the DSM-IV 138 In the ICD-10, 139 premenstrual tension or premenstrual syndrome is listed under the disorders Inhibitors,research,lifescience,medical of the genitourinary system. The term premenstrual syndrome is often used to describe the less severe presentations of the syndrome. These different terms describe a series of symptoms and signs Phosphoprotein phosphatase in women of reproductive age that occur during the luteal phase of their cycle and disappear on the first day or days of menstruation. In some women, these symptoms are limited to a few days before menstruation, while in others, they start at the time of ovulation. The clinical manifestations vary in severity, PMDD being characterized by quite severe changes in mood, with depression, anxiety, and suspiciousness; women tend to be irritable, cry, and feel desperate, with the impression of losing control of their existence. One of the diagnostic criteria for PMDD is impairment of quality of life.

Furthermore, as no absolute measures of brain activity are provided with BOLD, the relative change needs to be interpreted with caution. Pharmacologic fMRI is a potentially powerful methodology when integrated with well-designed

and informative pharmacologic paradigms. Neuroimaging genomics The application of fMRI in genetic paradigms is growing rapidly. Initial studies have examined Inhibitors,research,lifescience,medical genetic effects indirectly by comparing activation patterns in probands with schizophrenia, unaffected siblings, and healthy comparison subjects with no family history of schizophrenia. Such studies have demonstrated, for example, that there were abnormalities in siblings that were less severe than those seen in affected individuals. This supports the Inhibitors,research,lifescience,medical application of fMRI as a quantitative phenotypic marker of schizophrenia.4,15,26,27 The draft sequence of the human genome offers unprecedented opportunities for direct evaluation of the effects of genetic variability on brain activity. Early work exploiting this potential has demonstrated such effects in healthy people

by comparing activation patterns between genotypically characterized groups. Studies Inhibitors,research,lifescience,medical applying genetic strategies used functional polymorphisms to group individuals for comparisons. For example, a common Val108/158Met substitution in the gene for catechol-O-methyltransferase (COMT) leads to decreased activity of this enzyme in dopamine catabolism and has been linked to decreased prefrontal cortical activity. Studies therefore examined COMT val/met polymorphism and prefrontal cortex Inhibitors,research,lifescience,medical activation.28,29 Individuals homozygous for the met allele had diminished prefrontal and hippocampal engagement while performing episodic Inhibitors,research,lifescience,medical memory encoding and retrieval compared with val/val subjects. In schizophrenia, where disease risk is likely conferred by multiple interacting susceptibility genes, it is necessary to study convergent potential pathways from gene effects to clinical manifestations. Several at-risk genes implicated in schizophrenia are related

to neuronal function including COMT, dysbindin, neuregulin 1 (NRG1), BDNF, RGS4, and DISC-L Initial work in schizophrenia demonstrated effects of the COMT polymorphism on cognition and prefrontal function and risk for schizophrenia. Using a similar approach (-)-p-Bromotetramisole Oxalate a risk haplotype was examined in GRM3, a gene encoding a metabotropic glutamate receptor. The findings were of reduced neuronal function in prefrontal cortex and impaired activation in the hippocampus during http://www.selleckchem.com/products/PCI-24781.html performance of a verbal memory task. The risk allele in the NRG 1 promoter region was associated with decreased activation of prefrontal and temporal lobe cortex. This research has great potential for constructing mechanistic models for the pathophysiology of schizophrenia.

People with CG feel the world could be made right instantly

by the reappearance of the deceased, whereas those with Daporinad price Depression have no such illusions. We know much more about neurobiology of depression than grief, but initial studies show them to be different. Sleep disturbance is associated with REM sleep abnormalities in depression but not in CG.23 Activation of dopamine circuitry has been seen in CG24 and not in major depression. Also, importantly, medication treatment has differential effects on depression and grief symptoms.25 Table II outlines similarities and differences Inhibitors,research,lifescience,medical between grief and depression. TABLE II. Difference between grief and depression. Depression can co-occur with CG and exacerbate CG symptoms. Inhibition of positive emotions robs the person with CG of a source of emotional nourishment. The negative cognitive bias in depression increases the tendency to ruminate over the circumstances or consequences of the death. Depression saps energy and fuels avoidance behavior. Depression also interferes with interpersonal relationships, and Inhibitors,research,lifescience,medical companionship Inhibitors,research,lifescience,medical is an important facilitator of successful mourning.

In all of these ways co-occurring depression can worsen CG and interfere with its resolution. When death is violent, CG also needs to be differentiated from PTSD. When someone experiences the sudden unexpected death of a loved one, they may develop PTSD. However, this needs to be differentiated from CG as there is some overlap in symptoms. People with CG experience intrusive images of the deceased Inhibitors,research,lifescience,medical loved one. They often engage in avoidance behavior and feel estranged from others. Many report sleep disturbance or difficulty concentrating. Close confrontation

Inhibitors,research,lifescience,medical with death inevitably registers as a personal threat. However, fear of personal physical danger is very rare in CG. Instead, bereaved people primarily experience sadness and yearning focused on the sustaining relationship they lost. CG symptoms differ correspondingly from those of PTSD, yet conceptually, CG’s closest neighbor is PTSD, not depression, as CG, like PTSD is a specific kind of response to a specific kind of life event. That said, a physical trauma that threatens physical harm and causes heightened fear and hypervigilance, is a very different specific event than a loss. A physical trauma is second contained and limited in space and time such that distance in time and space markedly reduce the threat. By contrast, a loss is never over, and the response to loss is quite different from the response to danger. An important loss, by definition, affects a person’s experience of themselves and the world. Most people are deeply and immutably changed after losing a loved one. Experiencing a trauma is very different. Most people who experience trauma do not develop symptoms. Almost everyone who loses a loved one experiences grief.