Configuration-Specific Insight into Single-Molecule Conductance and Noise Data Revealed by the Principal Component Projection Method.

We explore the merits of neural network boosted, principal-component-projection-based, unsupervised data classification in single-molecule break junction measurements, demonstrating that this method identifies highly relevant trace classes according to the well-defined and well-visualized internal correlations of the data set. To this end, we investigate single-molecule structures exhibiting double molecular configurations, exploring the role of the leading principal components in the identification of alternative junction evolution trajectories. We show how the proper principal component projections can be applied to separately analyze the high- or low-conductance molecular configurations, which we exploit in 1/f-type noise measurements on bipyridine molecules. This approach untangles the unclear noise evolution of the entire data set, identifying the coupling of the aromatic ring to the electrodes through the π orbitals in two distinct conductance regions, and its subsequent uncoupling as these configurations are stretched.

Impact of comorbidities on survival following major injury across different types of road users.

BACKGROUND: While comorbidities and types of road users are known to influence survival in people hospitalised with injury, few studies have examined the association between comorbidities and survival in people injured in road traffic crashes. Further, few studies have examined outcomes across different types of road users with different types of pre-existing comorbidities. This study aims to examine differences in survival within 30 days of admission among different road user types with and without different pre-existing comorbidities. METHOD: Retrospective cohort study using data for all major road trauma cases were extracted from the NSW Trauma Registry Minimum Dataset (1 January 2013 - 31 July 2019) and linked to the NSW Admitted Patient Data Collection, and the NSW Registry of Births, Deaths and Marriages - death dataset. Pre-existing comorbidities and road user types were identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and Charlson Comorbidity Index in the Trauma Registry, hospital admission, and death datasets. Logistic regression was used to assess the associations between six types of road users (pedestrian, pedal cycle, two- and three-wheel motorcycle, car and pick-up truck, heavy vehicle and bus, and other types of vehicle) and death within 30 days of hospital admission while controlling for comorbidities. All models used 'car and pick-up truck driver/passenger' as the road user reference group and adjusted for demographic variables, injury severity, and level of impaired consciousness. RESULTS: Within 6253 traffic injury person-records (all aged ≥15 years old, ISS>12), and in final models, injured road users with major trauma who had a history of cardiovascular diseases (including stroke), diabetes mellitus, and higher Charlson Comorbidity Index score, were more likely to die, than those without pre-existing comorbidities. Furthermore, in final models, pedestrians were more likely to die than car occupants (OR: 1.68 - 1.77, 95CI%: 1.26 - 2.29 depending on comorbidity type). CONCLUSIONS: This study highlights the need to prioritize enhanced management of trauma patients with comorbidities, given the increasing prevalence of chronic medical conditions globally, together with actions to prevent pedestrian crashes in strategies to reach Vision Zero.

Structural Memory Effects in Gold-4,4'-Bipyridine-Gold Single-Molecule Nanowires.

We study the vulnerability of single-molecule nanowires against a temporary disconnection of the junction. To this end, we compare the room and low-temperature junction formation trajectories along the opening and closing of gold-4,4'-bipyridine-gold single-molecule nanowires. In the low-temperature measurements, the cross-correlations between the opening and subsequent closing conductance traces demonstrate a strong structural memory effect: around half of the molecular opening traces exhibit similar, statistically dependent molecular features as the junction is closed again. This means that the junction stays rigid and the molecule remains protruding from one electrode even after the rupture of the junction, and therefore, the same single-molecule junction can be reestablished if the electrodes are closed again. In the room-temperature measurements, however, weak opening-closing correlations are found, indicating a significant rearrangement of the junction after the rupture and the related loss of structural memory effects.

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

The morphology of ligamentous sacroiliac lesions - challenge to the antero-posterior compression mechanism.

AIM: This paper evaluates computer tomographic morphology of partial ligamentous lesions of the sacroiliac joint. We hypothesised that in antero-posterior compression (APC) injuries the anterior superior portion of the sacroiliac joint (SIJ) should open up the most as suggested by the vector forces outlined in the Young and Burgess classification. METHODS: All patients who underwent operative fixation of a ligamentous APC pelvic injury between July 2009 and December 2015 in a single Level-1 trauma centre were included. Patients were case matched (1:1) to controls without pelvic injury. SIJ width was measured by two independent reviewers at the anterior superior and anterior inferior part of the SIJ. Wilcoxon ranged test was applied for analysis. RESULTS: 70 patients (35 cases, 35 controls) were evaluated. Median inferior and superior SI joint widths were 5.27 (IQR 3.68-7.80) and 4.05 (IQR 3.13-5.31) mm in cases versus 2.24 (IQR 1.83-2.50) and 2.44 (IQR 2.14-2.65) mm in controls, respectively. The difference between the inferior and superior SI width in cases was larger than in controls (p-value < 0.01, median of -0.22 mm in the control group versus 1.51 mm in the cases). CONCLUSION: Our data suggests that the inferior part of the SIJ opens up after injury more, relative to its superior portion. The vector of the force involved in rotationally unstable pelvic injuries is unlikely to be antero-posterior if the force causes the SI joint to widen up inferiorly first. This should be considered in SIJ fixation and challenges the APC mechanism in pure ligamentous rotationally unstable pelvic ring injuries.

Voltage-Controlled Binary Conductance Switching in Gold-4,4'-Bipyridine-Gold Single-Molecule Nanowires.

We investigate gold-4,4'-bipyridine-gold single-molecule junctions with the mechanically controllable break junction technique at cryogenic temperature (T = 4.2 K). We observe bistable probabilistic conductance switching between the two molecular binding configurations, influenced both by the mechanical actuation and by the applied voltage. We demonstrate that the relative dominance of the two conductance states is tunable by the electrode displacement, whereas the voltage manipulation induces an exponential speedup of both switching times. The detailed investigation of the voltage-tunable switching rates provides an insight into the possible switching mechanisms.

The effect of haemorrhagic shock and resuscitation on fracture healing in a rabbit model: an animal study.

Aims: Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship. Materials and Methods: A total of 18 male New Zealand white rabbits underwent femoral osteotomy with intramedullary fixation with 'shock' (n = 9) and control (n = 9) groups. Shock was induced in the study group by removal of 35% of the total blood volume 45 minutes before resuscitation with blood and crystalloid. Fracture healing was monitored for eight weeks using serum markers of healing and radiographs. Results: Four animals were excluded due to postoperative complications. The serum concentration of osteocalcin was significantly elevated in the shock group postoperatively (p < 0.0001). There were otherwise no differences with regard to serum markers of bone healing. The callus index was consistently increased in the shock group on anteroposterior (p = 0.0069) and lateral (p = 0.0165) radiographs from three weeks postoperatively. The control group showed an earlier decrease of callus index. Radiographic scores were significantly greater in the control group (p = 0.0025). Conclusion: In a rabbit femoral osteotomy model with intramedullary fixation, haemorrhagic shock and resuscitation produced larger callus but with evidence of delayed remodelling. Cite this article: Bone Joint J 2018;100-B:1234-40.

An interobserver reliability comparison between the Orthopaedic Trauma Association's open fracture classification and the Gustilo and Anderson classification.

AIMS: To evaluate interobserver reliability of the Orthopaedic Trauma Association's open fracture classification system (OTA-OFC). PATIENTS AND METHODS: Patients of any age with a first presentation of an open long bone fracture were included. Standard radiographs, wound photographs, and a short clinical description were given to eight orthopaedic surgeons, who independently evaluated the injury using both the Gustilo and Anderson (GA) and OTA-OFC classifications. The responses were compared for variability using Cohen's kappa. RESULTS: The overall interobserver agreement was ĸ = 0.44 for the GA classification and ĸ = 0.49 for OTA-OFC, which reflects moderate agreement (0.41 to 0.60) for both classifications. The agreement in the five categories of OTA-OFC was: for skin, ĸ = 0.55 (moderate); for muscle, ĸ = 0.44 (moderate); for arterial injury, ĸ = 0.74 (substantial); for contamination, ĸ = 0.35 (fair); and for bone loss, ĸ = 0.41 (moderate). CONCLUSION: Although the OTA-OFC, with similar interobserver agreement to GA, offers a more detailed description of open fractures, further development may be needed to make it a reliable and robust tool. Cite this article: Bone Joint J 2018;100-B:242-6.

Reamed locked intramedullary nailing for studying femur fracture and its complications.

Morbidity associated with femur fractures in polytrauma patients is known to be high. The many unsolved clinical questions include the immunological effect of the fracture and its fixation, timing of fracture fixation, management of fracture non-union, effect of infection and critical size of bone defects. The aim of this study was to establish a clinically-relevant and reproducible animal model with regards to histological, biomechanical and radiological changes during bone healing. A custom-designed intramedullary nail with interlocking system (RabbitNail, RISystem AG, Davos Platz, Switzerland) was used for fixation, following femur fracture. New Zealand White rabbits were assigned to two groups: 1. closed fracture model (CF; non-survival model: n = 6, survival model: n = 3) with unilateral mid-shaft femur fracture created by blunt force; 2. osteotomy model (OT; survival model: n = 14) with unilateral transverse osteotomy creating femur fracture. There were no intraoperative complications and full-weight bearing was achieved in all survival rabbits. Significant periosteal reaction and callus formation were confirmed from 2 weeks postoperatively, with a significant volume formation (739.59 ± 62.14 mm3) at 8 weeks confirmed by micro-computed tomography (µ-CT). 2 months after fixation, there was no difference between the osteotomised and contralateral control femora in respect to the maximum torque (3.47 ± 0.35 N m vs. 3.26 ± 0.37 N m) and total energy (21.11 ± 3.09 N m × degree vs. 20.89 ± 2.63 N m × degree) required to break the femur. The data confirmed that a standardised internal fixation technique with an intramedullary nail for closed fracture or osteotomy produced satisfactory bone healing. It was concluded that important clinically-relevant studies can be conducted using this rabbit model.

Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Erratum to: 2016 WSES guidelines on acute calculous cholecystitis.

[This corrects the article DOI: 10.1186/s13017-016-0082-5.].

2016 WSES guidelines on acute calculous cholecystitis.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

Seeking the driver in tumours with apparent normal molecular profile on comparative genomic hybridization and targeted gene panel sequencing: what is the added value of whole exome sequencing?

BACKGROUND: Molecular tumour profiling technologies have become increasingly important in the era of precision medicine, but their routine use is limited by their accessibility, cost, and tumour material availability. It is therefore crucial to assess their relative added value to optimize the sequence and combination of such technologies. PATIENTS AND METHODS: Within the MOSCATO-01 trial, we investigated the added value of whole exome sequencing (WES) in patients that did not present any molecular abnormality on array comparative genomic hybridization (aCGH) and targeted gene panel sequencing (TGPS) using cancer specific panels. The pathogenicity potential and actionability of mutations detected on WES was assessed. RESULTS: Among 420 patients enrolled between December 2011 and December 2013, 283 (67%) patients were analysed for both TGPS and aCGH. The tumour sample of 25 (8.8%) of them presented a flat (or low-dynamic) aCGH profile and no pathogenic mutation on TGPS. We selected the first eligible 10 samples-corresponding to a heterogeneous cohort of different tumour types-to perform WES. This allowed identifying eight mutations of interest in two patients: FGFR3, PDGFRB, and CREBBP missense single-nucleotide variants (SNVs) in an urothelial carcinoma; FGFR2, FBXW7, TP53, and MLH1 missense SNVs as well as an ATM frameshift mutation in a squamous cell carcinoma of the tongue. The FGFR3 alteration had been previously described as an actionable activating mutation and might have resulted in treatment by an FGFR inhibitor. CREBBP and ATM alterations might also have suggested a therapeutic orientation towards epigenetic modifiers and ataxia-telangectasia and Rad3-related inhibitors, respectively. CONCLUSION: The therapeutic added value of performing WES on tumour samples that do not harbour any genetic abnormality on TGPS and aCGH might be limited and variable according to the histotype. Alternative techniques, including RNASeq and methylome analysis, might be more informative in selected cases.

Evolution of nanoscale clusters in γ' precipitates of a Ni-Al-Ti model alloy.

The evolution of phase separation and ordering processes determines the structure and properties of Ni-based superalloys. Here we use atom probe tomography to clarify the origin of γ particles occurring in ordered (L12) γ' precipitates in a Ni86.1Al8.5Ti5.4 alloy. Particularly, we elucidate the evolution from nanoscaled Ni-rich heterogeneities (Ni-rich clusters) to γ spheres and then γ plates inside γ' precipitates from the compositional and the thermodynamic point of view. We find that Ni supersaturation of γ' precipitates is relieved by formation of Ni-rich clusters, which results in an energetically more favorable state. Subsequently, coalescence introduces necking between the Ni-rich clusters and leads to the formation of γ particles. Our results demonstrate that phase separation of γ' precipitates is characterized by different stages with various governing driving forces.

Vascular endothelial growth factor levels in tears of patients with retinal vein occlusion.

PURPOSE: We measured vascular endothelial growth factor (VEGF) levels in tear fluid and serum in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: Eight patients with RVO due to secondary macular oedema were examined. VEGF levels were measured by enzyme-linked immunosorbent assay. All patients had a full ophthalmic examination (visual acuity, slit lamp biomicroscopy, perimetry, and fluorescein angiography). Central retinal thickness (CRT) was examined using optical coherence tomography (OCT). Tear and serum samples were collected and examinations were performed at diagnosis and 1 and 4 weeks later. RESULTS: VEGF levels in the tears of RVO eyes were significantly higher than in fellow eyes at diagnosis and after both 1 and 4 weeks (paired t test, p1 = 0.01, p2 = 0.02, p3 = 0.006). We found a weak but significant positive correlation between VEGF levels in tear fluid and serum of patients with RVO (r = 0.21), while this correlation tended to be stronger between the fellow eyes and serum levels (r = 0.33). CONCLUSION: To the best of our knowledge, we are the first to report an increased level of VEGF in the tear fluid of patients with RVO. Alterations of VEGF levels in tears may be useful for determining stages of RVO. This non-invasive and objective method may also be helpful for estimating the severity of macular oedema and efficacy of treatment.

Preventable mortality in geriatric hip fracture inpatients.

There is a high rate of mortality in elderly patients who sustain a fracture of the hip. We aimed to determine the rate of preventable mortality and errors during the management of these patients. A 12 month prospective study was performed on patients aged > 65 years who had sustained a fracture of the hip. This was conducted at a Level 1 Trauma Centre with no orthogeriatric service. A multidisciplinary review of the medical records by four specialists was performed to analyse errors of management and elements of preventable mortality. During 2011, there were 437 patients aged > 65 years admitted with a fracture of the hip (85 years (66 to 99)) and 20 died while in hospital (86.3 years (67 to 96)). A total of 152 errors were identified in the 80 individual reviews of the 20 deaths. A total of 99 errors (65%) were thought to have at least a moderate effect on death; 45 reviews considering death (57%) were thought to have potentially been preventable. Agreement between the panel of reviewers on the preventability of death was fair. A larger-scale assessment of preventable mortality in elderly patients who sustain a fracture of the hip is required. Multidisciplinary review panels could be considered as part of the quality assurance process in the management of these patients.

Damage control surgery for abdominal emergencies.

BACKGROUND: Damage control surgery is a management sequence initiated to reduce the risk of death in severely injured patients presenting with physiological derangement. Damage control principles have emerged as an approach in non-trauma abdominal emergencies in order to reduce mortality compared with primary definitive surgery. METHODS: A PubMed/MEDLINE literature review was conducted of data available over the past decade (up to August 2013) to gain information on current understanding of damage control surgery for abdominal surgical emergencies. Future directions for research are discussed. RESULTS: Damage control surgery facilitates a strategy for life-saving intervention for critically ill patients by abbreviated laparotomy with subsequent reoperation for delayed definitive repair after physiological resuscitation. The six-phase strategy (including damage control resuscitation in phase 0) is similar to that for severely injured patients, although non-trauma indications include shock from uncontrolled haemorrhage or sepsis. Minimal evidence exists to validate the benefit of damage control surgery in general surgical abdominal emergencies. The collective published experience over the past decade is limited to 16 studies including a total of 455 (range 3-99) patients, of which the majority are retrospective case series. However, the concept has widespread acceptance by emergency surgeons, and appears a logical extension from pathophysiological principles in trauma to haemorrhage and sepsis. The benefits of this strategy depend on careful patient selection. Damage control surgery has been performed for a wide range of indications, but most frequently for uncontrolled bleeding during elective surgery, haemorrhage from complicated gastroduodenal ulcer disease, generalized peritonitis, acute mesenteric ischaemia and other sources of intra-abdominal sepsis. CONCLUSION: Damage control surgery is employed in a wide range of abdominal emergencies and is an increasingly recognized life-saving tactic in emergency surgery performed on physiologically deranged patients.

Update on the definition of polytrauma.

PURPOSE: The definition and use of the term "polytrauma" is inconsistent and lacks validation. This article describes the historical evolution of the term and geographical differences in its meaning, examines the challenges faced in defining it adequately in the current context, and summarizes where the international consensus process is heading, in order to provide the trauma community with a validated and universally agreed upon definition of polytrauma. CONCLUSION: A lack of consensus in the definition of "polytrauma" was apparent. According to the international consensus opinion, both anatomical and physiological parameters should be included in the definition of polytrauma. An Abbreviated Injury Scale (AIS) based anatomical definition is the most practical and feasible given the ubiquitous use of the system. Convincing preliminary data show that two body regions with AIS >2 is a good marker of polytrauma-better than other ISS cutoffs, which could also indicate monotrauma. The selection of the most accurate physiological parameters is still underway, but they will most likely be descriptors of tissue hypoxia and coagulopathy.