Comparison of Human Surrogate Responses in Underbody Blast Loading Conditions.

Impact biomechanics research in occupant safety predominantly focuses on the effects of loads applied to human subjects during automotive collisions. Characterization of the biomechanical response under such loading conditions is an active and important area of investigation. However, critical knowledge gaps remain in our understanding of human biomechanical response and injury tolerance under vertically accelerated loading conditions experienced due to underbody blast (UBB) events. This knowledge gap is reflected in anthropomorphic test devices (ATDs) used to assess occupant safety. Experiments are needed to characterize biomechanical response under UBB relevant loading conditions. Matched pair experiments in which an existing ATD is evaluated in the same conditions as a post mortem human subject (PMHS) may be utilized to evaluate biofidelity and injury prediction capabilities, as well as ATD durability, under vertical loading. To characterize whole body response in the vertical direction, six whole body PMHS tests were completed under two vertical loading conditions. A series of 50th percentile hybrid III ATD tests were completed under the same conditions. Ability of the hybrid III to represent the PMHS response was evaluated using a standard evaluation metric. Tibial accelerations were comparable in both response shape and magnitude, while other sensor locations had large variations in response. Posttest inspection of the hybrid III revealed damage to the pelvis foam and skin, which resulted in large variations in pelvis response. This work provides an initial characterization of the response of the seated hybrid III ATD and PMHS under high rate vertical accelerative loading.

Quantum Optomechanics in a Liquid.

We measure the quantum fluctuations of a single acoustic mode in a volume of superfluid He that is coupled to an optical cavity. Specifically, we monitor the Stokes and anti-Stokes light scattered by a standing acoustic wave that is confined by the cavity mirrors. The intensity of these signals (and their cross-correlation) exhibits the characteristic features of the acoustic wave's zero-point motion and the quantum backaction of the intracavity light. While these features are also observed in the vibrations of solid objects and ultracold atomic gases, their observation in superfluid He opens the possibility of exploiting the remarkable properties of this material to access new regimes of quantum optomechanics.

Optical absorption of composition-tunable InGaAs nanowire arrays.

InGaAs nanowire (NW) arrays have emerged as important active materials in future photovoltaic and photodetector applications, due to their excellent electronic properties and tunable band gap. Here, we report a systematic investigation of the optical absorption characteristics of composition-tunable vertical InGaAs NW arrays. Using finite-difference time-domain simulations we first study the effect of variable composition (Ga-molar fraction) and NW array geometry (NW diameter, period, fill factor) on the optical generation rate. NWs with typical diameters in the range of ∼100-250 nm lead to generation rates higher than the equivalent bulk case for moderate fill factors (NW period of ∼0.3-0.8 µm), while slightly smaller fill factors and increased diameters are required to maintain high generation rates at increased Ga-molar fraction. The optical absorption was further measured using spectrally resolved ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy on NW arrays transferred to transparent substrates. Interestingly, large variations in Ga-molar fraction (0 < x(Ga) < 0.5) have a negligible influence, while minute changes in NW diameter of less than ±20 nm affect the absorption spectra very strongly, leading to pronounced shifts in the peak absorption energies by more than ∼700 meV. These results clearly highlight the much larger sensitivity of the optical absorption behavior to geometric parameters rather than to variations in the electronic band gap of the underlying NW array.

A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer.

Background: Perioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients. Patients and methods: We analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients. Results: A risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17-0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21-0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17-0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17-0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23-0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02-0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies. Conclusion: The identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.

[Pacemaker, defibrillator and co : Perioperative handling of cardiac implantable electronic devices]. / Schrittmacher, Defi & Co : Der perioperative Umgang mit "cardiac implantable electronic devices".

The number of patients treated with cardiac implantable electronic devices (CIED) is continously increasing. Knowledge of the medical indications and technical mode of functioning of these devices is a basic prerequisite for the safe perioperative care of this patient cohort. The CIEDs are subjected to a multitude of disturbing influences in the perioperative setting. This can result in potentially dangerous complications, such as exit block and oversensing. The safe performance of interventions is possible as long as some basic rules are followed. An interdisciplinary approach involving all participating disciplines is necessary in order to adequately deal with the high demands placed on the logistics.

[Are There Gender-Specific Differences in Complications Following Abdominal Surgery?]. / Gibt es geschlechterspezifische Unterschiede bei Komplikationen in der offenen Viszeralchirurgie?

Studies in mice indicate gender-specific differences in surgical complications with a distinct advantage for females. In patient care, however, gender has been an underrated aspect of complication management in abdominal surgery as far. Proven differences between the sexes regarding anatomy, hormonal regulation, constitutional polymorphisms, immune response and psychology suggest different types and incidence of complications and seem to justify studies on the topic. This review aims to compare a selection of current original articles reporting on complications following abdominal surgery separately for the genders. However, data in the literature are sparse and in part very heterogeneous. With data on colorectal carcinoma being most comprehensive, for stomach, oesophagus and finally pancreas fewer data can be found. Summing up all organ systems, the following cautious conclusions can be drawn. Men tend to suffer from postoperative complications more frequently. Men have more cases of anastomotic leakage, whereas women suffer from anastomotic stenosis more often. Currently, however, existing data do not justify any adaptation of patient management. Thus, taking gender aspects into account in designing new trials is paramount in order to obtain robust gender-specific data on incidence and types of complications.

[Gender Aspects in Gastrointestinal Tumours and Their Prognosis in Regard to Multimodal Treatment Concepts]. / Genderaspekte bei Tumoren des Gastrointestinaltrakts und ihre Prognose, insbesondere im Rahmen multimodaler Therapiekonzepte.

Systematic analyses of gender effects in gastrointestinal malignancies are currently lacking, partly because sex and gender have not been used as stratification criteria in major studies on the topic. It is, however, indisputable that gastrointestinal tumours differ in risk factors, incidence and prognosis between the genders. This review summarises the most important findings on differences related to biological sex and sociocultural gender and discusses anatomic specifics with immediate significance for surgical interventions. Epidemiological differences in upper gastrointestinal malignancies are most prominent in regard to histological subtypes, directly affecting diagnostics, therapy, and prognosis. Women have a better prognosis in many of these tumour subtypes. For colorectal carcinoma, sex hormones, specifically oestrogens, appear to play a distinct role in tumourigenesis. Histopathological analysis of the expression of oestrogen receptor beta (ERß) in the tumour tissue has attracted interest since it was shown that women with low ERß expression have a better prognosis than men with comparable ERß status. Data on the higher incidence of right-sided colon carcinoma and non-polypoid neoplasms in women could lead to improved screening programmes. Men and women cite differing reasons for avoidance of screening colonoscopies, thus gender specific approaches could improve colon cancer prevention programmes. Data on differing bioavailability of 5-fluorouracil between the genders are useful to minimise adverse effects of chemotherapy and should be accounted for in dosage. Further systematic analysis of gender effects on gastrointestinal tumours is warranted and would be a substantial step towards personalised oncological surgery.

Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas.

BACKGROUND: Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. METHODS: In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. RESULTS: Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. CONCLUSIONS: Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker.

A specific expression profile of heat-shock proteins and glucose-regulated proteins is associated with response to neoadjuvant chemotherapy in oesophageal adenocarcinomas.

BACKGROUND: Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response. METHODS: Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR. RESULTS: CTX response strongly correlated with survival (P=0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P=0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P=0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P=0.016 and P=0.004). CONCLUSION: Our findings may enhance the understanding of CTX response mechanisms, might be helpful to predict CTX response and might have translational relevance as they highlight the role of potentially targetable cellular stress proteins in the context of CTX response.

Preoperative therapy of esophagogastric cancer: the problem of nonresponding patients.

INTRODUCTION: Preoperative treatment is nowadays standard for locally advanced esophagogastric cancer in Europe. Surprisingly, little attention has been paid to nonresponders so far. The aim of our retrospective exploratory study was the comparison of responder, nonresponder, and primary resected patients in respect of outcome considering the tumor entity. PATIENTS AND METHODS: From 2001-2011, 607 patients with locally advanced esophagogastric carcinoma (adenocarcinoma of the esophagogastric junction (AEG), n = 293; squamous cell cancer (SCC), n = 111; gastric cancer, n = 203) after preoperative treatment (n = 281) or primary resection (n = 326) were included. Histopathological response evaluation (Becker criteria) was available for 263. RESULTS: A total of 76/263 (28.9 %) were responders (<10 % residual tumor). There was an association of response with increased R0 resections (p < 0.001) but also with a higher complication rate (p = 0.008) compared to nonresponse and primary surgery. Mortality was not influenced. Increased R0 resections after response were confirmed in every tumor entity (AEG, p = 0.010; SCC, p = 0.023; gastric cancer, p = 0.006). Median survival was best for responders with 43.5 months [95 % confidence interval (CI), 27.9-59.1], followed by nonresponders with 24.3 months (95 % CI, 21.6-27.0) and primary resected patients with 20.8 months (95 % CI, 17.7-23.9; p = 0.002). AEG (p = 0.012) and gastric cancer (p = 0.017) revealed identical results, but in the subgroup of SCC, the survival of nonresponders (median, 11.6 months; 95 % CI, 6.9-16.3) was even worse than for primary resected patients (median, 23.8 months; 95 % CI, 1.7-46.0; p = 0.012). CONCLUSION: The histopathological response rate was low. Generally, nonresponding patients with AEG or gastric cancer seem not to have a disadvantage compared to primary resected patients, but nonresponders with SCC have a worse prognosis, which strengthens the demand for a critical patient selection in surgery for this tumor entity.

Controlling fast transport of cold trapped ions.

We realize fast transport of ions in a segmented microstructured Paul trap. The ion is shuttled over a distance of more than 10(4) times its ground state wave function size during only five motional cycles of the trap (280 µm in 3.6 µs). Starting from a ground-state-cooled ion, we find an optimized transport such that the energy increase is as low as 0.10±0.01 motional quanta. In addition, we demonstrate that quantum information stored in a spin-motion entangled state is preserved throughout the transport. Shuttling operations are concatenated, as a proof-of-principle for the shuttling-based architecture to scalable ion trap quantum computing.

New trends for staging and therapy for localized gastroesophageal cancer: the role of PET.

Treatment options for localized gastroesophageal cancers reach from limited resection to multimodality treatment. Accurate clinical assessment, prognostic and predictive information are needed to select the most appropriate treatment approach. Positron emission tomography (PET) in combination with computed tomography (CT) in a hybrid imaging modality PET-CT may refine the staging accuracy and add prognostic information. Moreover, experiences from diverse centers indicate that PET also might improve significantly the assessment of response to preoperative chemotherapy and chemoradiotherapy. This article outlines the current value of PET in the staging and multidisciplinary care of gastroesophageal cancer. At this stage, it remains unclear whether the prognosis of patients can be improved by implementing PET in the management of localized disease. Prospective multicenter studies have to be carried out to validate metabolic cut-off values and to prove the benefit of PET-guided treatment decisions.

[Lipid emulsion therapy for local anaesthetic toxicity. (LipidRescue)]. / Lipidlösungen zur Therapie der Lokalanästhetikaintoxikation. (LipidRescue).

Intoxication due to local anaesthetic drugs poses a rare but potentially life-threatening complication. In particular long-acting local anaesthetics can cause refractory cardiac arrest due to their lipophilic properties. This is often preceded by neurological symptoms such as confusion, vertigo and tonic-clonic seizures. The clinical efficacy of lipid emulsions in resuscitation from local anaesthetic toxicity has been documented in multiple publications. The injection of local anaesthetics should be stopped immediately upon the first presentation of symptoms. Securing the airway is mandatory to avoid hypoxia and concurrent acidosis. A seizure should be controlled with adequate doses of anticonvulsants. In case of cardiac arrest standard protocols for cardiopulmonary resuscitation have to be implemented immediately. The use of lipid emulsion can then be initiated as a supplement to standard resuscitation. It is recommended that lipid emulsions are instantly accessible in all facilities where local anaesthetics are administered.

Limited resection and free jejunal graft interposition for squamous cell carcinoma of the cervical oesophagus.

BACKGROUND: Therapeutic strategies for cervical oesophageal squamous cell carcinoma (SCC) are controversial. Treatment options range from definitive radiotherapy to multimodal treatment. Outcome after limited resection and reconstruction with a free jejunal graft interposition was evaluated retrospectively. METHODS: Patients with clinical T1-4 Nx M0 tumours treated between 1986 and 2006 were included. RESULTS: Of 109 patients, 94 underwent preoperative chemoradiotherapy and 15 had a primary resection. Complete or partial preservation of the larynx was achieved in 93 patients (85.3 per cent). Minor and major complications occurred in 74.3 per cent, with 44.0 per cent of all patients having more than one complication. Reoperation was necessary in 29.4 per cent. The 30-day mortality rate was 1.8 per cent, and the in-hospital mortality rate 2.8 per cent. The complete R0 resection rate was 72.5 per cent. Median overall survival was 34.3 months; 1-, 3- and 5-year survival rates were 83.8, 47.0 and 47.0 per cent respectively. Survival was not influenced by complications (P = 0.401) or reoperation (P = 0.428). CONCLUSION: Despite high complication and reoperation rates, the mortality rate was low, even after preoperative chemoradiation. This complex surgical strategy is a treatment option for cervical SCC in oncological centres with an infrastructure providing multidisciplinary management.

Eperythrozoon coccoides: influence on course of infection of Plasmodium chabaudi in mouse.

Mice infected with Plasmodium chabaudi obtained from two sources were found to be contaminated with Eperythrozoon coccoides. At each transfer of blood parasitized with plasmodia, eperythrozoa were also passed. In the presence of these organisms, the malarial infection assumed a low-level, chronic course infrequently resulting in death of the mice. When the eperythrozoa were eliminated through treatment with oxophenarsine hydrochloride, the malarial infection took an acute course always ending in death.

Porphyromonas gingivalis Impairs Oral Epithelial Barrier through Targeting GRHL2.

Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis (Pg)-induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides (Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, ß-proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.

Unraveling the role of connective tissue growth factor in diabetic nephropathy.

Marked upregulation of the secreted extracellular matrix-associated protein connective tissue growth factor (CTGF) in the glomerulus coincides with the onset of diabetic nephropathy. Recent studies, including the one by Yokoi et al., shed light on the role of CTGF in glomerular injury.

Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial.

Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.