Universal slow dynamics of chemical reaction networks.

Understanding the emergent behavior of chemical reaction networks (CRNs) is a fundamental aspect of biology and its origin from inanimate matter. A closed CRN monotonically tends to thermal equilibrium, but when it is opened to external reservoirs, a range of behaviors is possible, including transition to a new equilibrium state, a nonequilibrium state, or indefinite growth. This study shows that slowly driven CRNs are governed by the conserved quantities of the closed system, which are generally far fewer in number than the species. Considering both deterministic and stochastic dynamics, a universal slow-dynamics equation is derived with singular perturbation methods and is shown to be thermodynamically consistent. The slow dynamics is highly robust against microscopic details of the network, which may be unknown in practical situations. In particular, nonequilibrium states of realistic large CRNs can be sought without knowledge of bulk reaction rates. The framework is successfully tested against a suite of networks of increasing complexity and argued to be relevant in the treatment of open CRNs as chemical machines.

Instantaneous normal modes of glass-forming liquids during the athermal relaxation process of the steepest descent algorithm.

Understanding glass formation by quenching remains a challenge in soft condensed matter physics. Recent numerical studies on steepest descent dynamics, which is one of the simplest models of quenching, revealed that quenched liquids undergo slow relaxation with a power law towards mechanical equilibrium and that the late stage of this process is governed by local rearrangements of particles. These advances motivate the detailed study of instantaneous normal modes during the relaxation process because the glassy dynamics is considered to be governed by stationary points of the potential energy landscape. Here, we performed a normal mode analysis of configurations during the steepest descent dynamics and found that the dynamics is driven by almost flat directions of the potential energy landscape at long times. These directions correspond to localized modes and we characterized them in terms of their statistics and structure using methods developed in the study of local minima of the potential energy landscape.

Gas-liquid phase separation at zero temperature: mechanical interpretation and implications for gelation.

The relationship between glasses and gels has been intensely debated for decades; however, the transition between these two phases remains elusive. To investigate a gel formation process in the zero-temperature limit and its relation to the glass phase, we conducted numerical experiments on athermal quasistatic decompression. During decompression, the system experiences a cavitation event similar to phase separation and this is a gelation process at zero temperature. A normal mode analysis revealed that the phase separation is signaled by the vanishing of the lowest eigenenergy, similar to plastic events of glasses under shear. One primary difference from the shear-induced plasticity is that the vanishing mode experiences a qualitative change in its spatial energy distribution at the phase separation point. These findings enable us to define the glass-gel phase boundary based on mechanics.

Vibrational density of states of jammed packing at high dimensions: Mean-field theory.

Several mean-field theories predict that the Hessian matrix of amorphous solids converges the Wishart matrix in the limit of the large spatial dimensions d→∞. Motivated by these results, we calculate here the density of states of random packing of harmonic spheres by mapping the Hessian of the original system to the Wishart matrix. We compare our result with that of previous numerical simulations of harmonic spheres in several spatial dimensions d=3, 5, and 9. For small pressure p≪1 (near jamming), we find a good agreement even in d=3, and obtain better agreements in larger d, suggesting that the approximation becomes exact in the limit d→∞.

[A case of metastatic melanoma in the gallbladder].

Malignant melanoma is an aggressive tumor with a high potential for distant metastases. Autopsy studies have shown that gallbladder metastases are found in 15% of patients. However, metastatic melanoma of the gallbladder is rarely discovered in living patients. A 73-year-old man was reported. The patient underwent surgical removal of malignant melanoma on his back and lymphadenectomy of the axillary lymph nodes. In addition, the patient developed cutaneous metastases to the right axillary and the middle of the chest 1.5 years after the surgery. Consequently, nivolumab chemotherapy was started. A computed tomography (CT) scan showed a well-enhanced mass in the gallbladder 4 months after. Abdominal ultrasonography revealed a 13-mm hypoechoic heterogeneous mass in the gallbladder with a hyperechoic layer on the mass surface. Magnetic resonance imaging demonstrated that the gallbladder tumor showed high signal intensity on T1-weighted images, low signal intensity on T2-weighted images, and high signal intensity on diffusion-weighted images. Positron emission tomography-CT revealed the slight uptake of fluorodeoxyglucose at the tumor. Endoscopic ultrasonography showed a hypoechoic tumor infiltrating the submucosal layer. The patient underwent open cholecystectomy. Examination of the resected specimens revealed a black, nodular-type tumor in the gallbladder body. The histopathological diagnosis was malignant melanoma. It was judged as metastatic melanoma of the gallbladder.

Novel elastic instability of amorphous solids in finite spatial dimensions.

Recently, progress has been made in the understanding of anomalous vibrational excitations in amorphous solids. In the lowest-frequency region, the vibrational spectrum follows a non-Debye quartic law, which persists up to zero frequency without any frequency gap. This gapless vibrational density of states (vDOS) suggests that glasses are on the verge of instability. This feature of marginal stability is now highlighted as a key concept in the theories of glasses. In particular, the elasticity theory based on marginal stability predicts the gapless vDOS. However, this theory yields a quadratic law and not the quartic law. To address this inconsistency, we presented a new type of instability, which is different from the conventional one, and proposed that amorphous solids are marginally stable considering the new instability in the preceding study [M. Shimada, H. Mizuno and A. Ikeda, Soft Matter, 2020, 16, 7279]. In this study, we further extend and detail the results for these instabilities. By analyzing various examples of disorder, we demonstrate that real glasses in finite spatial dimensions can be marginally stable by the proposed novel instability.

Vibrational spectrum derived from local mechanical response in disordered solids.

The low-frequency vibrations of glasses are markedly different from those of crystals. These vibrations have recently been categorized into two types: spatially extended vibrations, whose vibrational density of states (vDOS) follows a non-Debye quadratic law, and quasilocalized vibrations (QLVs), whose vDOS follows a quartic law. The former are explained by elasticity theory with quenched disorder and microscopic replica theory as being a consequence of elastic instability, but the origin of the latter is still debated. Here, we show that the latter can also be directly derived from elasticity theory with quenched disorder. We find another elastic instability that the theory encompasses but that has been overlooked so far, namely, the instability of the system against a local dipolar force. This instability gives rise to an additional contribution to the vDOS, and the spatial structure and energetics of the mode originating from this instability are consistent with those of the QLVs. Finally, we construct a model in which the additional contribution to the vDOS follows a quartic law.

Low-frequency vibrations of jammed packings in large spatial dimensions.

Amorphous packings prepared in the vicinity of the jamming transition play a central role in theoretical studies of the vibrational spectrum of glasses. Two mean-field theories predict that the vibrational density of states g(ω) obeys a characteristic power law, g(ω)∼ω^{2}, called the non-Debye scaling in the low-frequency region. Numerical studies have, however, reported that this scaling breaks down at low frequencies, due to finite-dimensional effects. In this study, we prepare amorphous packings of up to 128000 particles in spatial dimensions from d=3 to d=9 to characterize the range of validity of the non-Debye scaling. Our numerical results suggest that the non-Debye scaling is obeyed down to a frequency that gradually decreases as d increases, and possibly vanishes for large d, in agreement with mean-field predictions. We also show that the prestress is an efficient control parameter to quantitatively compare packings across different spatial dimensions.

Laparoscopic repair of a large perineal hernia after laparoscopic abdominoperineal resection: A case report.

A 75-year-old woman underwent laparoscopic abdominoperineal resection. Four months after abdominoperineal resection, the patient complained of a perineal bulge and urination disorder. Abdominal CT showed protrusion of the small intestine and bladder to the perineum. The patient underwent laparoscopic hernia repair with mesh. The size of the hernial orifice was 7.0 × 9.0 cm, and it had no solid rim. The mesh was tacked ventrally to the pectineal ligament and dorsally to the sacrum, and then sutured on the lateral side. The hernia has not recurred 10 months after the operation. Laparoscopic repair is a good treatment choice for secondary perineal hernia and fixing the mesh to the pectineal ligament, and the sacrum prevents the mesh from sagging.

Anomalous vibrational properties in the continuum limit of glasses.

The low-temperature thermal properties of glasses are anomalous with respect to those of crystals. These thermal anomalies indicate that the low-frequency vibrational properties of glasses differ from those of crystals. Recent studies revealed that, in the simplest model of glasses, i.e., the harmonic potential system, phonon modes coexist with soft localized modes in the low-frequency (continuum) limit. However, the nature of low-frequency vibrational modes of more realistic models is still controversial. In the present work, we study the Lennard-Jones (LJ) system using large-scale molecular-dynamics (MD) simulation and establish that the vibrational property of the LJ glass converges to coexistence of the phonon modes and the soft localized modes in the continuum limit as in the case of the harmonic potential system. Importantly, we find that the low-frequency vibrations are rather sensitive to the numerical scheme of potential truncation, which is usually implemented in the MD simulation, and this is the reason why contradictory arguments have been reported by previous works. We also discuss the physical origin of this sensitiveness by means of a linear stability analysis.

Solitary choroidal metastasis from gastric adenocarcinoma: a case report.

BACKGROUND: Metastatic choroidal carcinomas that originated from the gastrointestinal tract are extremely rare. We report a case of suspected solitary choroidal metastasis from gastric adenocarcinoma. CASE PRESENTATION: The patient was a 60-year-old man who had undergone laparoscopic distal gastrectomy with D1+ lymphadenecetomy for gastric cancer. The clinical stage was T1bN0M0 (TNM classification), but the pathological stage was T4aN0M0 beyond expectation. Adjuvant chemotherapy with oral Tegafur, Gimeracil, Oteracil potassium (TS-1®) was initiated. But he suddenly complained of decreased visual acuity in his right eye about 8 months later. This was suspected to be caused by choroidal metastasis of gastric adenocarcinoma. Chemotherapy with paclitaxel (PTX) and intensity-modulated radiotherapy (IMRT) achieved complete remission and spared the patient from going blind. CONCLUSIONS: This case demonstrates that we should be aware of the possibility of choroidal metastases, when visual symptoms arise during treatment of gastric cancer.

Underwater robotic suturing.

BACKGROUND: Laparoscopic and robotic surgeries have become popular, and this popularity is increasing. However, the environment in which such surgeries are performed is rarely discussed. Similar to arthrosurgery performed in water, artificial ascites could be a new environment for laparoscopic surgery. This study was performed to determine whether robotic surgery is applicable to complicated suturing underwater. MATERIAL AND METHODS: A da Vinci Surgical System S was used. A weighted fabric sheet was placed at the bottom of a tank. Identical sets were made for each environment: One tank was dry, and the other was filled with water. The suturing task involved placement of a running silk suture around the perimeter of a small circle. The task was performed eight times in each environment. The task time and integrity score were determined. The integrity score was calculated by evaluating accuracy, tightness, thread damage, and uniformity; each factor was evaluated using a five-point scale. RESULTS: Although statistically significant differences were not shown in either task time or integrity score between the underwater and air environments, robotic suturing underwater is not inferior to performance in air. CONCLUSIONS: The feasibility of robotic suturing underwater was confirmed under the herein-described experimental conditions.

Going back to home to die: does it make a difference to patient survival?

BACKGROUND: Many patients wish to stay at home during the terminal stage of cancer. However, there is concern that medical care provided at home may negatively affect survival. This study therefore explored whether the survival duration differed between cancer patients who received inpatient care and those who received home care. METHODS: We retrospectively investigated the place of care/death and survival duration of 190 cancer patients after their referral to a palliative care consultation team in a Japanese general hospital between 2007 and 2012. The patients were classified into a hospital care group consisting of those who received palliative care in the hospital until death, and a home care group including patients who received palliative care at home from doctors in collaboration with the palliative care consultation team. Details of the place of care, survival duration, and patient characteristics (primary site, gender, age, history of chemotherapy, and performance status) were obtained from electronic medical records, and analyzed after propensity score matching in the place of care. RESULTS: Median survival adjusted for propensity score was significantly longer in the home care group (67.0 days, n = 69) than in the hospital care group (33.0 days, n = 69; P = 0.0013). Cox's proportional hazard analysis revealed that the place of care was a significant factor for survival following adjustment for covariates including performance status. CONCLUSIONS: This study suggests that the general concern that home care shortens the survival duration of patients is not based on evidence. A cohort study including more known prognostic factors is necessary to confirm the results.

Saline-filled laparoscopic surgery: A basic study on partial hepatectomy in a rabbit model.

BACKGROUND: There is still a poor understanding of the effects of pneumoperitoneum with insufflation of carbon dioxide gas (CO2) on malignant cells, and pneumoperitoneum has a negative impact on cardiopulmonary responses. A novel saline-filled laparoscopic surgery (SAFLS) is proposed, and the technical feasibility of performing saline-filled laparoscopic partial hepatectomy (LPH) was evaluated in a rabbit model. MATERIAL AND METHODS: Twelve LPH were performed in rabbits, with six procedures performed using an ultrasonic device with CO2 pneumoperitoneum (CO2 group) and six procedures performed using a bipolar resectoscope (RS) in a saline-filled environment (saline group). Resection time, CO2 and saline consumption, vital signs, blood gas analysis, complications, interleukin-1 beta (IL-1ß) and C-reactive protein (CRP) levels were measured. The effectiveness of the resections was evaluated by the pathological findings. RESULTS: LPH was successfully performed with clear observation by irrigation and good control of bleeding by coagulation with RS. There were no significant differences in all perioperative values, IL-1ßand CRP levels between the two groups. All pathological specimens of the saline group showed that the resected lesions were coagulated and regenerated as well as in the CO2 group. CONCLUSIONS: SAFLS is feasible and provides a good surgical view with irrigation and identification of bleeding sites.

Evaluation of A Novel Information-Sharing Instrument for Home-Based Palliative Care: A Feasibility Study.

AIM: To examine the feasibility and usefulness of a novel region-based pathway: the Regional Referral Clinical Pathway for Home-Based Palliative Care. METHOD: This was a feasibility study to evaluate the frequency of variances and the perceived usefulness of pathway using in-depth interviews. All patients with cancer referred to the palliative care team between 2011 and 2013 and received home care services were enrolled. RESULT: A total of 44 patients were analyzed, and pathway was completed in all the patients. The target outcome was achieved in 61.4% while some variances occurred in 54.5%. Nine categories were identified as the usefulness of the pathway, such as reviewing and sharing information and promoting communication, education, motivation, and relationships. CONCLUSION: This novel pathway is feasible and seems to be useful.

Robot-assisted thyroidectomy with novel camera-port retractor.

We performed gasless transaxillary robot-assisted thyroidectomy with a novel camera-port retractor (CP retractor). Herein, we describe the new instrument and its efficacy, which was evaluated by performing robot-assisted thyroidectomy. From October 2009 to August 2012, a total of 12 patients underwent robot-assisted thyroidectomy using the da Vinci Surgical System. The CP retractor was used in all cases, and we use the Maryland bipolar forceps and the microbipolar forceps on both arms for dissection of the surrounding tissues as well as for cutting and coagulation to avoid injury to the vessels and the nerves. The CP retractor provided excellent visualization without robotic arm instrument interference. The novel retractor is useful and safe, and the use of bipolar instruments is an effective option for robotic dissection around the nerves in the robot-assisted thyroidectomy.

[A case of advanced gastric cancer diagnosed as stage IV responding to combined modality therapy and surviving for a long duration].

A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

Robot-assisted thoracoscopic hybrid esophagectomy in the semi-prone position under pneumothorax.

We performed robot-assisted thoracoscopic hybrid esophagectomy using the da Vinci Surgical System and demonstrated the potential benefit of this minimally invasive lymphadenectomy. Between April 2010 and October 2011, four patients with intrathoracic esophageal cancer underwent hybrid esophagectomy in the semi-prone position using a 3-arm standard da Vinci and a conventional thoracoscopic maneuver. All thoracoscopic procedures were completed using a robot-assisted technique. Robot-assisted thoracoscopic esophagectomy in the semi-prone position is safe and technically feasible. A hybrid procedure that combined standard da Vinci with conventional thoracosopic maneuvers overcomes the difficulties associated with using a standard da Vinci.

[Use of orally disintegrating olanzapine tablet for patients with cancerous peritonitis and postoperative gastric cancer receiving home palliative care].

In May, 2009, a man in his 30s presented to the department of outpatient palliative care of this hospital. His chief complaints were of severe nausea and abdominal fullness associated with cancerous peritonitis following surgery for gastric cancer. Abdominal fullness was reduced after the initiation of a continued subcutaneous administration of octreotide acetate, but combination therapy with metoclopramide and domperidone did not relieve nausea. The administration of olanzapine orally disintegrating tables (OLZ-ODT) at a dose of 10 mg twice daily was associated with the tendency to reduce nausea. As the symptoms were relieved, palliative care at his home was initiated. The patient's self-discontinuation of OLZ-ODT because the nausea was relieved resulted in its aggravation, but it was relieved again when the administration was resumed. Subsequently, home care was possible for approximately two and half a months without aggravation. Maintaining nausea control well leads to higher-quality care. OLZ-ODT appears to not only be effective for relieving nausea associated with cancerous peritonitis, but is also important for disseminating palliative care at home.

Resected pleomorphic carcinoma of the gallbladder.

Pleomorphic carcinoma is a rare lesion and the literature contains few reports of pleomorphic carcinoma of the gallbladder. The present study reports a rare case of primary pleomorphic carcinoma of the gallbladder for which we were able to perform curative surgery. A 77-year-old woman with dementia developed nausea and anorexia, and computed tomography demonstrated irregular thickening of the gallbladder wall. Drip infusion cholangiography and endoscopic retrograde cholangiopancreatography revealed no stenosis of the common and intrahepatic bile ducts. We suspected carcinoma of the gallbladder without lymph node metastasis and invasion to the common bile duct. We guessed it to be resectable and performed open laparotomy. At operation, the fundus of the gallbladder was adherent to the transverse colon, but no lymph node and distant metastases were detected. Therefore, we performed curative cholecystectomy with partial colectomy. Histopathology and immunostaining showed coexistence of an adenocarcinoma, squamous cell carcinoma and sarcomatous tumor of spindle-shaped cell, as well as transition zones between these tumors. We diagnosed stage I pleomorphic carcinoma of the gallbladder. No recurrence has been observed for one and a half years. The biological behavior of pleomorphic carcinoma of the gallbladder remains unknown. It will be necessary to accumulate more case reports of this tumor in order to define diagnostic criteria.