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Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real‐time measurements of fluorescent and non‐fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real‐time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post‐transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real‐time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery. [ABSTRACT FROM AUTHOR]

Background: Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week. Methods: Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long‐term liver perfusion machine and moreover supportive in the biomedical engineering process. Results: Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 ("poor" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver). Conclusion: Knowing the feasible ranges (upper‐ and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. Methods: A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. Results: A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. Conclusions: These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed. [ABSTRACT FROM AUTHOR]

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood‐based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti‐FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate. [ABSTRACT FROM AUTHOR]

Introduction: The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week. Methods: Porcine livers (n = 42) were procured and perfused with blood at 34°C following aseptic technique and standard operating procedures. The antimicrobial prophylaxis was adapted and improved in a step‐wise manner taking into account the pathogens that were detected during the development phase. Piperacillin‐Tazobactam was applied as a single dose initially and modified to continuous application in the final protocol. In addition, the perfusion machine was improved to recapitulate partially the host's defense system. The final protocol was tested for infection prevention during one week of perfusion. Results: During the development phase, microbial contamination occurred in 27 out of 39 (69%) livers with a mean occurrence of growth on 4 ± 1.6 perfusion days. The recovered microorganisms suggested an exogenous source of microbial contamination. The antimicrobial agents (piperacillin/tazobactam) could be maintained above the targeted minimal inhibitory concentration (8‐16 mg/L) only with continuous application. In addition to continuous application of piperacillin/tazobactam, partial recapitulation of the host immune system ex situ accompanied by strict preventive measures for contact and air contamination maintained sterility during one week of perfusion. Conclusion: The work demonstrates feasibility of sterility maintenance for one week during ex situ normothermic liver perfusion. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate if the time of day a cholecystectomy was performed affects in-hospital complication rates and mortality. Methods: A national quality measurement database was retrospectively studied. Study period was 2010 to 2017. The inclusion criteria were operatively treated cholecystitis or another benign disease of the gallbladder. Further, the time of day the operation was performed must have been documented. We defined nighttime as all interventions performed between 7PM until 6AM. A total of 11′459 patients were included. Development of any complication during hospitalization and in-hospital mortality was the main outcomes. The first part of the study was solely descriptive. In the second part, we applied a 1:1 case–control-matching. A matched group of 274 pairs were further investigated. Results: Only 8.4% of the procedures were performed during nighttime. Complications occurred in 6.7% of all patients. We found twice as many complications in the nighttime group compared to the daytime group. Mortality was 0.56% during daytime and 0.52% during nighttime. In a matched-pair analysis, however, we found no significant differences in the overall mortality rate nor in the occurrence of complications when comparing day- vs. nighttime operations. Conclusions: We found twice as many complications in the nighttime group (12%) compared to the daytime group (6.1%), mainly related to patient risk factors. In contrast to common apprehension, however, nighttime cholecystectomies were not associated with higher mortality rates. [ABSTRACT FROM AUTHOR]

Background: The landscape of surgical training has been subject to many changes over the past 15 years. This study examines resident satisfaction, determinants of satisfaction, demographics, working hours and the teaching rate of common operations in a longitudinal fashion with the aim to identify trends, shortcomings and possible ways to improve the current training system. Methods: The Swiss Medical Association administers an annual survey to all Swiss residents to evaluate the quality of postgraduate medical training (yearly respondents: 687–825, response rate: 68–72%). Teaching rates for general surgical procedures were obtained from the Swiss association for quality management in surgery. Results: During the study period (2003–2018), the number of surgical residents (408–655 (+61%)) and graduates in general surgery per year (42–63 (+50%)) increased disproportionately to the Swiss population. While the 52 working hour restriction was introduced in 2005 reported average weekly working hours did not decline (59.9–58.4 h (−3%)). Workplace satisfaction (6 being highest) rose from 4.3 to 4.6 (+7%). Working climate and leadership culture were the main determinants for resident satisfaction. The proportion of taught basic surgical procedures fell from 24.6 to 18.9% (−23%). Conclusions: The number of residents and graduates in general surgery has risen markedly. At the same time, the proportion of taught operations is diminishing. Despite the introduction of working hour restrictions, the self-reported hours never reached the limit. The low teaching rate combined with the increasing resident number represents a major challenge to the maintenance of the current training quality. [ABSTRACT FROM AUTHOR]

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes. [ABSTRACT FROM AUTHOR]

The ability of the liver to restore its original volume following tissue loss has been associated with the Hippo‐YAP1 pathway, a key controller of organ size. Yes‐associated protein 1 (YAP1)—a growth effector usually restrained by Hippo signaling—is believed to be of particular importance; however, its role in liver regeneration remains ill‐defined. To explore its function, we knocked down YAP1 prior to standard 70%‐hepatectomy (sHx) using a hepatocyte‐specific nanoformulation. Knockdown was effective during the major parenchymal growth phase (S‐phase/M‐phase peaks at 32 hours/48 hours post‐sHx). Liver weight gain was completely suppressed by the knockdown at 32 hours, but was reaccelerated toward 48 hours. Likewise, proliferative markers, Ccna2/b2 and YAP1 target gene expression were downregulated at 32 hours, but re‐elevated at 48 hours post‐sHx. Nonetheless, knockdown slightly compromised survival after sHx. When assessing a model of resection‐induced liver failure (extended 86%‐hepatectomy, eHx) featuring deficient S‐ and M‐phase progression, YAP1 was not induced at 32 hours, but upregulated at 48 hours post‐eHx, confirming its dissociation from M‐phase regulation. Therefore, YAP1 is vital to push hepatocytes into cycle and through the S‐phase, but is not required for further cell cycle progression during liver regeneration. The examination of YAP1 in human livers suggested its function is conserved in the regenerating mammalian liver. [ABSTRACT FROM AUTHOR]

Abstract: Defective regeneration of small‐for‐size (SFS) liver remnants and partial grafts remains a key limiting factor in the application of liver surgery and transplantation. Exogenous melatonin (MLT) has protective effects on hepatic ischemia‐reperfusion injury (IRI), but its influence on graft regeneration is unknown. The aim of the study is to investigate the role of MLT in IRI and graft regeneration in settings of partial liver transplantation. We established three mouse models to study hepatic IRI and regeneration associated with partial liver transplantation: (I) IR+PH group: 60 minutes liver ischemia (IR) plus 2/3 hepatectomy (PH); (II) IR+exPH group: 60 minutes liver IR plus extended hepatectomy (exPH) associated with the SFS syndrome; (III) SFS‐LT group: Arterialized 30% SFS liver transplant. Each group was divided into MLT or vehicle‐treated subgroups. Hepatic injury, inflammatory signatures, liver regeneration, and animal survival rates were assessed. MLT reduced liver injury, enhanced liver regeneration, and promoted interleukin (IL) 6, IL10, and tumor necrosis factor‐α release by infiltrating, inflammatory Ly6C+ F4/80+ monocytes in the IR+PH group. MLT‐induced IL6 significantly improved hepatic microcirculation and survival in the IR+exPH model. In the SFS‐LT group, MLT promoted graft regeneration and increased recipient survival along with increased IL6/GP130‐STAT3 signaling. In IL6−/− mice, MLT failed to promote liver recovery, which could be restored through recombinant IL6. In the IR+exPH and SFS‐LT groups, inhibition of the IL6 co‐receptor GP130 through SC144 abolished the beneficial effects of MLT. MLT ameliorates SFS liver graft IRI and restores regeneration through monocyte‐released IL6 and downstream IL6/GP130‐STAT3 signaling. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety of surgical performance by residents of different training level performing common general surgical procedures. Methods: Data were consecutively collected from all patients undergoing general surgical procedures such as laparoscopic cholecystectomy, laparoscopic appendectomy, inguinal, femoral and umbilical hernia repair from 2005 to 2011 at the Department of Surgery of the University Hospital of Zurich, Switzerland. The operating surgeons were grouped into junior residents, senior residents and consultants. The comprehensive complication index (CCI) representing the overall number and severity of all postoperative complications served as primary safety endpoint. A multivariable linear regression analysis was used to analyze differences between groups. Additionally, we focused on the impact of senior residents assisting junior residents on postoperative outcome comparing to consultants. Results: During the observed time, 2715 patients underwent a general surgical procedure. In 1114 times, a senior resident operated and in 669 procedures junior residents performed the surgery. The overall postoperative morbidity quantified by the CCI was for consultants 5.0 (SD 10.7), for senior residents 3.5 (8.2) and for junior residents 3.6 (8.3). After adjusting for possible confounders, no difference between groups concerning the postoperative complications was detected. There is also no difference in postoperative complications detectable if junior residents were assisted by consultants then if assisted by senior residents. Discussion: Patient safety is ensured in general surgery when performed by surgical junior residents. Senior residents are able to adopt the role of the teaching surgeon in charge without compromising patients' safety. [ABSTRACT FROM AUTHOR]

Background: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. Methods: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. Results: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 ( p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality ( p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. Conclusions: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus. Methods: A systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations. Results: A total of 157 full texts were screened. Thirty-seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal-directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia. Conclusions: The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol. [ABSTRACT FROM AUTHOR]

Background We aim to assess the incidence, current treatment, and outcome of diverticulitis in highly immunosuppressed lung transplant recipients. Methods Retrospective analysis of a prospective database of 403 lung transplant recipients transplanted between 1992 and 2013 with a mean follow-up of 100 months ( SD 58.0). Results 4.46% of lung transplant recipients (n=18) developed diverticulitis. Eight lung transplant recipients developed uncomplicated diverticulitis, which were all treated successfully with antibiotics. Three patients (37.5%) underwent elective sigmoid resection with severe Grade 3b complications after two of five (40%) surgical procedures. Diverticulitis recurrence occurred in five patients (60%). In total, 10 lung transplant recipients presented with 11 episodes of perforated diverticulitis with a 30-day mortality rate of 9.1%. Hartmann procedure was performed in eight lung transplant recipients. Sigmoid resection with primary anastomosis and protective ileostomy was performed in three patients with Hinchey I. Two of these patients developed anastomotic leakage with a secondary Hartmann procedure. Conclusion Due to high leakage rate after resection with primary anastomosis and protective ileostomy in our cohort of lung transplant recipients with perforated diverticulitis, the Hartmann procedure seems to be the safer option. In contrast, in uncomplicated diverticulitis, non-operative treatment can be considered as a safe and highly successful treatment option, even for recurrences. [ABSTRACT FROM AUTHOR]

Authors' response to 'Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry' Abbreviations ALPPS associating liver partition and portal vein ligation for staged hepatectomy BSA body surface area sFLR standardized future liver remnant share sTLV standardized total liver volumen We have read with interest the letter to the editor written by Olthof et al.1 regarding our study based on the ALPPS registry to identify predictive growth factors of the future liver remnant (FLR).2 The authors challenge the methodology and clinical relevance of our findings. Standardized total liver volume (sTLV) is helping to estimate the total liver volume using BSA. [Extracted from the article]

Introduction: Morbidity and mortality rates after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are important quality parameters to compare peritoneal surface malignancy centers. A major problem to assess postoperative outcomes among centers is the inconsistent reporting due to two coexisting systems, the diagnose-based common terminology criteria for adverse events (CTCAE) classification and the therapy-oriented Clavien-Dindo classification. We therefore assessed and compared both reporting systems. Patients and Methods: Complications after CRS/HIPEC were recorded in 147 consecutive patients and independently graded by an expert board using both systems. In a next step, a group of residents, experienced surgeons, and medical oncologists evaluated a set of twelve real complications, either with the Clavien-Dindo or CTCAE classification. Results: The postoperative complication rate after CRS/HIPEC was 37 % (54/147), 6.8 % (10/147) were reoperated, and three (2 %) patients died. The most frequent complications were intestinal fistula or abscess, pulmonary complications, and ileus. Grading of complications with the CTCAE classification resulted in a significantly higher major morbidity rate compared to the Clavien-Dindo classification (25 vs. 8 %, p = 0.001). Evaluating a set of complications, residents, surgeons, and oncologists correctly assessed significantly more complications with the Clavien-Dindo compared to the CTCEA classification ( p < 0.001). In addition, all participants evaluated the Clavien-Dindo classification as more simple. Residents ( p < 0.001) and surgeons ( p < 0.01) required less time with the Clavien-Dindo classification; there was no difference for oncologist. Conclusion: In conclusion, our data indicate that there is a different interpretation of severity grades of complications after CRS/HIPEC between the two classifications. There is a need for a common language in the field of CRS/HIPEC, which should be defined by a new consensus to compare surgical outcomes. [ABSTRACT FROM AUTHOR]

Background: Standardized reporting of intraoperative adverse events is important to enhance transparency. To the best of our knowledge, there is no validated definition and classification of intraoperative complications. Methods: We conducted a two-round Delphi study to develop a definition and classification of intraoperative complications. Experts were contacted by email and sent a link to the online questionnaire. In a pilot study, two independent raters applied the definition and classification in a sample of 60 surgical interventions of low, intermediate, and high complexity and evaluated practicability. Interrater agreement of the classification was determined (raw categorical agreement, weighted kappa, and intraclass correlation). Results: In the Delphi study, 40 of 52 experts (77 % return rate) from 14 countries took part in each round. The Delphi study resulted in a comprehensive definition of intraoperative complications as any deviation from the ideal intraoperative course occurring between skin incision and skin closure. The classification foresees four grades depending on the need for treatment (no need, grade I; need for treatment, grade II) and the severity of the complication (life-threatening/permanent disability, grade III; death, grade IV). The pilot study showed good practicability (6 on a 7-point scale) and a high raw agreement of 87 %, a weighted kappa of 0.83 [95 % confidence interval (CI) 0.73-0.94] and an intraclass correlation coefficient of 0.83 (95 % CI 0.73-0.90). Conclusions: While the Delphi process enabled to develop definitions and classification of intraoperative complications by severity, further research including a multicentre international full-scale validation needs to be conducted with the ultimate goal to contribute to standardized reporting in surgical practice and research. [ABSTRACT FROM AUTHOR]

Background: Reporting of surgical outcomes is important for healthcare decision making and includes the reporting of complications. Several classifications have been proposed and validated for postoperative, but not intraoperative, complications. The aim of the present study is to assess the current practice of complication reporting in surgical trials. Methods: We evaluated the reporting of intra- and postoperative complications in all registered randomized controlled trials that included investigate surgery or invasive interventions in at least one study arm and were published in 2010 in the Annals of Surgery, JAMA Surgery, and the British Journal of Surgery. Results: A total of 46 trials were identified; intra- and postoperative complications were reported separately in 42 % and pooled in 15 %. In 37 % intraoperative, in 2 % postoperative, and in 4 % both intra- and postoperative, complications were not reported at all. Exact definitions were provided in 13 % for intraoperative and in 50 % for postoperative complications. A classification was used in 9 % for intra- and in 54 % for postoperative complications, most frequently according to severity. The type of intervention (surgical vs. other) or whether the primary outcome was the assessment of complications had no significant impact on reporting definitions of adverse events. Conclusions: Intraoperative complications are frequently pooled with postoperative complications, ill-defined, or not reported at all, hampering informed decision making. As further research, we propose to develop and validate a classification of intraoperative complications. This will facilitate the evaluation of safety and the continuous quality control of surgical interventions with the ultimate goal to contribute to patient safety. [ABSTRACT FROM AUTHOR]