bluuebunny/crossref_metadata_2025 huggingface dataset:
Metaphysics of Pain; Semantics of ‘Pain’
Authors: Pelman Alik
Published: April 2015

Functionalism is often used to identify mental states with physical states. A particularly powerful case is Lewis's analytical functionalism. Kripke's view seriously challenges any such identification. The dispute between Kripke and Lewis's views boils down to whether the term ‘pain’ is rigid or nonrigid. It is a strong intuition of ours that if it feels like pain it is pain, and vice versa, so that ‘pain’ should designate, with respect to every possible world, all and only states felt as pain. Hence, in order to settle the dispute, we need to check which of the two – Kripke's use of ‘pain’ as rigid, or Lewis's use of ‘pain’ as nonrigid – better meets this intuition. I show that, despite crucial differences in both their semantic and metaphysical assumptions, surprisingly, both views meet this intuition equally well. Thus it appears that this question of rigidity cannot, in principle, be solved, and so, at least with respect to this particular dispute, the jury is still out on whether mental states are identical to physical states.
Life memories and the ability to act: the meaning of autonomy and participation for older people when living with chronic illness
Authors: Hedman Maria , Pöder Ulrika , Mamhidir Anna‐Greta , Nilsson Annika , Kristofferzon Marja‐Leena , Häggström Elisabeth
Published: April 2015

There is a lack of knowledge about how older people living with chronic illness describe the meaning of autonomy and participation, indicating a risk for reduced autonomy and participation in their everyday life. The purpose of this study was to describe the meaning of autonomy and participation among older people living with chronic illness in accordance with their lived experience. The design was descriptive with a phenomenological approach guided by Giorgi's descriptive phenomenological psychological method. Purposive sampling was used, and 16 older people living with chronic illness who lived in an ordinary home participated in individual interviews. The findings showed that the meaning of autonomy and participation among the older people emerged when it was challenged and evoked emotional considerations of the lived experience of having a chronic illness. It involved living a life apart, yet still being someone who is able, trustworthy and given responsibility – still being seen and acknowledged. The meaning of autonomy and participation was derived through life memories and used by the older people in everyday life for adjustment or adaption to the present life and the future. Our conclusion is that autonomy and participation were considered in relation to older people's life memories in the past, in their present situation and also their future wishes. Ability or disability is of less importance than the meaning of everyday life among older people. We suggest using fewer labels for limitations in everyday life when caring for older people and more use of the phrase ‘ability to act’ in different ways, based on older people's descriptions of the meaning of autonomy and participation.
The residual risk of transfusion‐transmitted cytomegalovirus infection associated with leucodepleted blood components
Authors: Seed C. R. , Wong J. , Polizzotto M. N. , Faddy H. , Keller A. J. , Pink J.
Published: April 2015

Background and Objectives

Cytomegalovirus poses a risk to transfusion safety as its transmission to an immunocompromised recipient may lead to significant clinical sequelae. Once infection is established, it is lifelong and generally asymptomatic. Strategies to reduce the risk of transfusion‐transmitted CMV (TT‐CMV) include donor serological testing and blood component leucodepletion to deplete the transmissible reservoir. We estimate the residual risk for non‐CMV antibody screened, leucodepleted (LD‐only) fresh blood components.

Materials and Methods

We established an approach to estimate the risk of TT‐CMV under various scenarios. We estimated the probability of an infectious component, for both red cells and platelets, as a function of the observed WBC filter failure rate and the probability that such a unit was also contaminated with infectious virus.

Results

Using this model, the estimated combined residual risk of LD‐only red cell and platelet units was very low, 1 in 13 575 000 (95%CI:1 in 1 344 167 000–1 in 1 730 000) as was the individual residual risk estimate for LD‐only red cells, 1 in 7 790 000 (95%CI: 1 in 771 307 000–1 in 993 000) and LD‐only platelets, where a zero risk was estimated (95%CI: 0–1 in 1 074 000).

Conclusion

We describe a novel approach to assess the residual risk of LD‐only components. This can be applied generally using local data. Our risk estimate for LD‐only blood components in Australia is below the threshold of 1 in 1 million, generally considered negligible. This provides a useful indicator of the relative safety of LD‐only components to assist clinical decisions when serologically screened inventory is unavailable.
Cardioprotective effect of hyperthyroidism on the stunned rat heart during ischaemia–reperfusion: energetics and role of mitochondria
Authors: Ragone María Inés , Bonazzola Patricia , Colareda Germán A. , Consolini Alicia E.
Published: April 2015

New Findings

What is the central question of this study?

Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca2+ handling of the postischaemic stunned heart?

What is the main finding and its importance?

Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium–calcium exchanger and mitochondrial K+ channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia.

Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3′‐triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia–reperfusion. Rats were injected s.c. daily with 20 μg kg−1 triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no‐flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca2+ from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low‐[Na+] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium–calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam‐induced dysfunction in HpT hearts was reduced by ciclosporin, suggesting a dependance on activation of the mitochondrial permeability transition pore. Blockade of the mitochondrial Ca2+ uniporter with Ru360 reduced P/Ht and PICR to ∼10% in both HpT and EuT hearts. Blockade of mitochondrial K+ channels with 5‐hydroxydecanoate increased LVEDP and reduced PICR and P/Ht in HpT hearts, while it only increased LVEDP in EuT hearts. The results suggest that hyperthyroidism prevents the stunning with high dependence on the mitochondrial sodium–calcium exchanger and mitochondrial K+ channels. Both HpT and EuT hearts showed a similar and critical role of the uniporter. The HpT hearts have a slow sarcoplasmic reticulum Ca2+ loss and low mitochondrial Ca2+ uptake.
Time-Independent Plasticity Based on Thermodynamic Equilibrium and Its Stability
Authors: Yang Q. , Chang Q. , Liu Y. R. , Feng X. Q.
Published: April 2015

Within the thermodynamic framework with internal variables by Rice (1971, “Inelastic Constitutive Relations for Solids: An Internal Variable Theory and Its Application to Metal Plasticity,” J. Mech. Phys. Solids, 19(6), pp. 433–455), Yang et al. (2014, “Time-Independent Plasticity Related to Critical Point of Free Energy Function and Functional,” ASME J. Eng. Mater. Technol., 136(2), p. 021001) established a model of time-independent plasticity of three states. In this model, equilibrium states are the states with vanishing thermodynamic forces conjugate to the internal variables, and correspond to critical points of the free energy or its complementary energy functions. Then, the conjugate forces play a role of yield functions and further lead to the consistency conditions. The model is further elaborated in this paper and extended to nonisothermal processes. It is shown that the incremental stress–strain relations are fully determined by the local curvature of the free energy or its complementary energy functions at the critical points, described by the Hessian matrices. It is further shown that the extended model can be well reformulated based on the intrinsic time in the sense of Valanis (1971, “A Theory of Viscoplasticity Without a Yield Surface, Part I. General Theory,” Arch. Mech., 23(4), pp. 517–533; 1975, “On the Foundations of the Endochronic Theory of Viscoplasticity,” Arch. Mech., 27(5–6), pp. 857–868), by taking the intrinsic time as the accumulated length of the variation of the internal variables during inelastic processes. It is revealed within this framework that the stability condition of equilibrium directly leads to Drucker (1951, “A More Fundamental Approach to Stress–Strain Relations,” First U.S. National Congress of Applied Mechanics, pp. 487–497) and Il'yushin (1961, “On a Postulate of Plasticity,” J. Appl. Math. Mech., 25(2), pp. 746–750) inequalities, by introducing the consistency condition into the work of Hill and Rice (1973, “Elastic Potentials and the Structure of Inelastic Constitutive Laws,” SIAM J. Appl. Math., 25(3), pp. 448–461). Generalized inequalities of Drucker (1951, “A More Fundamental Approach to Stress–Strain Relations,” First U.S. National Congress of Applied Mechanics, pp. 487–497) and Il'yushin (1961, “On a Postulate of Plasticity,” J. Appl. Math. Mech., 25(2), pp. 746–750) for nonisothermal processes are established straightforwardly based on the connection.
Experimental observation of a generalized Gibbs ensemble
Authors: Langen Tim , Erne Sebastian , Geiger Remi , Rauer Bernhard , Schweigler Thomas , Kuhnert Maximilian , Rohringer Wolfgang , Mazets Igor E. , Gasenzer Thomas , Schmiedmayer Jörg
Published: April 2015

Detecting multiple temperatures

Most people have an intuitive understanding of temperature. In the context of statistical mechanics, the higher the temperature, the more a system is removed from its lowest energy state. Things become more complicated in a nonequilibrium system governed by quantum mechanics and constrained by several conserved quantities. Langen
et al.
showed that as many as 10 temperature-like parameters are necessary to describe the steady state of a one-dimensional gas of Rb atoms that was split into two in a particular way (see the Perspective by Spielman).

Science
, this issue p.
207
; see also p.
185
Bully for
Brontosaurus
!
Authors: Balter Michael
Published: April 2015

A comprehensive study of one branch of the dinosaur family tree resurrects
Brontosaurus
as a valid genus.
Infectious cancer found in clams
Authors: Stokstad Erik
Published: April 2015

A single leukemia afflicts shellfish beds across hundreds of kilometers, puzzling biologists.
New technologies for translational research: Applying high-content screening in cancer research and personalized medicine
Authors: Linding Rune , Kubicek Stefan , Periyasamy Giridharan
Published: April 2015

New techniques and technologies are constantly being introduced that deepen our understanding of disease and therapeutic pathways. Biochemical screening methods have long been used in drug discovery labs, and more recently also in academic settings. Recent advances in both imaging technology and high throughput automation have led to the development of high-content screening (HCS) and integrated liquid handling systems that have broad application in academia and industry. These advances in image acquisition and automation have transformed numerous fields and have yielded increased data capture and throughput. This webinar will discuss how integrated HCS imaging systems that have been coupled with novel computer modeling are being applied to systems biology, translational cancer research, and personalized medicine.
Middle Miocene closure of the Central American Seaway
Authors: Montes C. , Cardona A. , Jaramillo C. , Pardo A. , Silva J. C. , Valencia V. , Ayala C. , Pérez-Angel L. C. , Rodriguez-Parra L. A. , Ramirez V. , Niño H.
Published: April 2015

Early closing between oceans

The Central American Seaway, which once separated the Panama Arc from South America, may have closed 10 million years earlier than is believed. Montes
et al.
report that certain minerals of Panamanian provenance began to appear in South America during the Middle Miocene, 15 to 13 million years ago (see the Perspective by Hoorn and Flantua). The presence of the minerals indicates that rivers were flowing from the Panama Arc into the shallow marine basins of northern South America. One interpretation of this finding is that large-scale ocean flow between the Atlantic and Pacific had ended by then. If this is true, then many models of paleo-ocean circulation and biotic exchange between the Americas need to be reconsidered.

Science
, this issue p.
226
; see also p.
186
Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding
Authors: Xue Yali , Prado-Martinez Javier , Sudmant Peter H. , Narasimhan Vagheesh , Ayub Qasim , Szpak Michal , Frandsen Peter , Chen Yuan , Yngvadottir Bryndis , Cooper David N. , de Manuel Marc , Hernandez-Rodriguez Jessica , Lobon Irene , Siegismund Hans R. , Pagani Luca , Quail Michael A. , Hvilsom Christina , Mudakikwa Antoine , Eichler Evan E. , Cranfield Michael R. , Marques-Bonet Tomas , Tyler-Smith Chris , Scally Aylwyn
Published: April 2015

Genomes in the mist

The mountain gorilla is an iconic species that is at high risk of extinction. Xue
et al.
have sequenced 13 gorillas from two different populations to probe their genetic diversity. The genomes show large tracts of homozygosity and the loss of highly deleterious genetic variants, indicating population bottlenecks and inbreeding. This loss of genetic diversity appears to have started over 20,000 years ago and may have been caused by changes in climate and human-associated effects.

Science
, this issue p.
242
Finding nascent proteins the right home
Authors: Kramer Günter , Guilbride D. Lys , Bukau Bernd
Published: April 2015

A protein complex prevents promiscuous targeting of nascent polypeptides in the cell

[Also see Report by

Gamerdinger
et al.

]
Comparison of Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Modified Live Vaccines against Heterologous Type 1 and Type 2 PRRSV Challenge in Growing Pigs
Authors: Kim Taeyeon , Park Changhoon , Choi Kyuhyung , Jeong Jiwoon , Kang Ikjae , Park Su-Jin , Chae Chanhee
Published: April 2015

The objective of the present study was to compare the efficacy of two commercial type 1 porcine reproductive and respiratory syndrome virus (PRRSV) modified live vaccines against heterologous type 1 and type 2 PRRSV challenge in growing pigs. Vaccination with a type 1 PRRSV vaccine reduced the level of viremia after type 1 PRRSV challenge but did not reduce the level of viremia after the type 2 PRRSV challenge in pigs. Increased levels of interleukin-10 (IL-10) stimulated by type 2 PRRSV coincided with the low numbers of type 2 PRRSV-specific interferon gamma-secreting cells (IFN-γ-SC) in vaccinated pigs after type 2 PRRSV challenge, whereas low levels of IL-10 stimulated by type 1 PRRSV coincided with high numbers of type 1 PRRSV-specific IFN-γ-SC in vaccinated pigs after type 1 PRRSV challenge. Additionally, vaccination with the type 1 PRRSV vaccine effectively reduced the lung lesions and type 1 PRRSV nucleic acids in type 1 PRRSV-challenged pigs but did not reduce lung lesions and type 2 PRRSV nucleic acids in type 2 PRRSV-challenged pigs. There were no significant differences between two commercial type 1 PRRSV vaccines against type 1 and type 2 PRRSV challenge based on virological results, immunological responses, and pathological outcomes. This study demonstrates that vaccinating pigs with the type 1 PRRSV vaccine provides partial protection against respiratory disease with heterologous type 1 PRRSV challenge but no protection with heterologous type 2 PRRSV challenge.
Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation
Authors: Da Costa Bruno , Sausset Alix , Munier Sandie , Ghounaris Alexandre , Naffakh Nadia , Le Goffic Ronan , Delmas Bernard
Published: April 2015

The influenza virus RNA-dependent RNA polymerase catalyzes genome replication and transcription within the cell nucleus. Efficient nuclear import and assembly of the polymerase subunits PB1, PB2, and PA are critical steps in the virus life cycle. We investigated the structure and function of the PA linker (residues 197 to 256), located between its N-terminal endonuclease domain and its C-terminal structured domain that binds PB1, the polymerase core. Circular dichroism experiments revealed that the PA linker by itself is structurally disordered. A large series of PA linker mutants exhibited a temperature-sensitive (
ts
) phenotype (reduced viral growth at 39.5°C versus 37°C/33°C), suggesting an alteration of folding kinetic parameters. The
ts
phenotype was associated with a reduced efficiency of replication/transcription of a pseudoviral reporter RNA in a minireplicon assay. Using a fluorescent-tagged PB1, we observed that
ts
and lethal PA mutants did not efficiently recruit PB1 to reach the nucleus at 39.5°C. A protein complementation assay using PA mutants, PB1, and β-importin IPO5 tagged with fragments of the
Gaussia princeps
luciferase showed that increasing the temperature negatively modulated the PA-PB1 and the PA-PB1-IPO5 interactions or complex stability. The selection of revertant viruses allowed the identification of different types of compensatory mutations located in one or the other of the three polymerase subunits. Two
ts
mutants were shown to be attenuated and able to induce antibodies in mice. Taken together, our results identify a PA domain critical for PB1-PA nuclear import and that is a “hot spot” to engineer
ts
mutants that could be used to design novel attenuated vaccines.

IMPORTANCE
By targeting a discrete domain of the PA polymerase subunit of influenza virus, we were able to identify a series of 9 amino acid positions that are appropriate to engineer temperature-sensitive (
ts
) mutants. This is the first time that a large number of
ts
mutations were engineered in such a short domain, demonstrating that rational design of
ts
mutants can be achieved. We were able to associate this phenotype with a defect of transport of the PA-PB1 complex into the nucleus. Reversion substitutions restored the ability of the complex to move to the nucleus. Two of these
ts
mutants were shown to be attenuated and able to produce antibodies in mice. These results are of high interest for the design of novel attenuated vaccines and to develop new antiviral drugs.
Group A streptococcal endophthalmitis complicating a sore throat in a 2-year-old child
Authors: Fitzgerald Felicity , Harris Kathryn , Henderson Robert , Edelsten Clive
Published: April 2015

A previously well 2-year-old presented to her general practitioner after 5 days of fever, lethargy, sore throat and a slightly red eye. A viral infection was diagnosed. Two days later, she re-presented with a swollen right eyelid and a moderately red eye. Oral amoxicillin and chloramphenicol eye drops were prescribed. The next day, marked periorbital swelling developed. She was admitted to hospital and parenteral ceftriaxone was started. Examination under anaesthetic showed injected globe diffuse corneal clouding and peripheral corneal opacities; ultrasound and CT suggested endophthalmitis. On transfer to a tertiary centre, intraocular vancomycin and subconjunctival cefuroxime were given. Aqueous fluid samples were positive for group AStreptococcus(GAS) by PCR, so parenteral clindamycin was added. GAS endophthalmitis was confirmed 1 day later from the positive intraocular fluid culture results. Visual evoked potentials revealed complete loss of vision. The eye was removed to limit potential spread. She made a good recovery postoperatively and was discharged on oral antibiotics.
Proximal-type epithelioid sarcoma—unusual presentation: unilateral vulvar mass
Authors: Rodrigues Ana Isabel , Lopes Helena Isabel , Lima Olinda , Marta Susana
Published: April 2015

Epithelioid sarcoma of the vulva is a very rare malignant soft tissue tumour, usually initially asymptomatic, which simulates a variety of benign lesions, leading to diagnosis only at later stages. Prognosis is generally poor. We report a case of a 55-year-old postmenopausal woman, who presented with rapid growth of an asymptomatic mass located in the left labia majora. Biopsy of the lesion revealed features characteristic of proximal-type epithelioid sarcoma. Ganglionar, adrenal, pulmonary and hepatic metastases were found at thoracoabdominopelvic CT scan. During hospitalisation, the patient’s clinical condition suffered rapid deterioration and she died on the 16th day of admission.
Not all secondary bone tumours are secondaries. Concurrent metastatic breast carcinoma and chondrosarcoma of the femur
Authors: Nath Preethy , Sankey Elizabeth , Murray Elisabeth , Kurup Harish
Published: April 2015

We present a case of metastatic adenocarcinoma of the breast in a patient who sustained a pathological fracture of the distal femur. Histology of the distal femur lesion excised at the time of endoprosthetic replacement confirmed this to be a primary chondrosarcoma. We have reviewed the literature and identified previously documented cases of concurrent breast carcinoma and chondrosarcoma of bone. A high index of suspicion is warranted and the diagnosis must be first confirmed before rushing to internal fixation (therapeutic or prophylactic) assuming them to be secondary bone lesions from the known primary cancer even in patients with multiple metastases.
Leucocyte adhesion deficiency type 1 with developmental delay secondary to CMV infection and filiation questions
Authors: Strickler Alexis , Gallo Silvanna , King Alejandra , Rosenzweig Sergio D
Published: April 2015

Leucocyte adhesion deficiency (LAD) is a group of rare autosomal recessive (<1:1 000 000 births) inherited disorders characterised by immune deficiency and peripheral neutrophilia. Three types of LAD syndrome have been distinguished. LAD type 1 (LAD-I) is the most common. It results from a mutation in the integrin β 2 (ITGB2) gene that codes the ITGB subunit (CD18 antigen). Since 1970, it has been reported in more than 300 children worldwide. It is characterised by delayed separation of the umbilical cord, recurrent bacterial and fungal infections, defective wound healing, blood neutrophilia and a high mortality rate at an early age. We report the second fatal case of an infant with LAD-I diagnosed in Chile, with developmental delay associated with a congenital cytomegalovirus infection. CD18/CD11 expression was normal. Genetic analysis of CD18 revealed a homozygous mutation in ITGB2, viz.c.1835G>T; p.C612F, and led us to suspect a biological parent other than the legal father and, therefore, an unwanted social situation.
Chemotherapy-induced acute psychosis in a patient with malignant germ cell tumour
Authors: Puangthong Umamon , Pongpirul Krit
Published: April 2015

A 25-year-old Thai woman with ovarian germ cell tumour presented with behavioural changes after receiving an intensive dose of neoadjuvant chemotherapy with bleomycin, etoposide and cisplatin, for a relapse. Her initial symptoms of mood fluctuation and insomnia were noticed while hospitalised for the third cycle, and became more severe. She was very irritable, highly distracted and forgetful. She exhibited flights of ideas and hyperactivity, including compulsive shopping. She also had paranoid ideations, auditory hallucinations, and thoughts of being wealthy and close to the prime minister. She was not depressed. She was diagnosed with axis I psychotic disorder not otherwise specified. The incremental dosage of olanzapine from 5 to 20 mg/day was given but failed to control her psychotic symptoms during the first week, and was therefore switched to risperidone. At 4 mg/day, her symptoms were dramatically controlled. This novel evidence suggests the rare possibility of an association between chemotherapy and the development of psychotic attacks.
Identification of vitamin C transporters in the human airways: a cross-sectional in vivo study
Authors: Larsson Nirina , Rankin Gregory D , Bicer Elif M , Roos-Engstrand Ester , Pourazar Jamshid , Blomberg Anders , Mudway Ian S , Behndig Annelie F
Published: April 2015

Objectives

Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs.

Setting and participants

Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre.

Primary and secondary outcome measures

The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers.

Results

Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations.

Conclusions

This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.
False negative rate for intraoperative sentinel lymph node frozen section in patients with breast cancer: a retrospective analysis of patients in a single Asian institution
Authors: Wong Jolene , Yong Wei Sean , Thike Aye Aye , Iqbal Jabed , Salahuddin Ahmed Syed , Ho Gay Hui , Madhukumar Preetha , Tan Benita Kiat Tee , Ong Kong Wee , Tan Puay Hoon
Published: April 2015

Background and objective

Intraoperative frozen section of the sentinel lymph node (SLN) in clinically node negative breast cancer patients detects metastatic disease and enables axillary lymph node dissection to be performed in the same operative setting. Internationally, the false negative rate (FNR) for SLN biopsy ranges from 5.5% to 43%. The size of SLN metastasis has been identified as a key factor affecting FNR. We review our institutional experience on the accuracy of intraoperative SLN biopsy.

Methods

Data were collected retrospectively from patients undergoing SLN biopsy performed at Singapore General Hospital. The SLN was identified using blue dye, radioisotope or both. Frozen section was performed intraoperatively. When SLN was positive for metastasis on frozen section, completion axillary clearance was performed. False negative cases were defined as patients in whom a negative frozen section result was obtained, whose final permanent paraffin section was positive. We determined the FNR of SLN frozen section and evaluated the factors associated with it.

Results

A total of 2202 SLN biopsies were performed between January 2005 and June 2012. There were 89 false negative cases, of which there were 23 (25.8%) cases of isolated tumour cells (ITCs), 49 (55.1%) cases of micrometastasis, and 17 (19.1%) cases of macrometastasis. The overall FNR was 13.5%. FNR was 79.3% in ITCs, 59.8% in micrometastasis, and 3.1% in macrometastatic disease. Non-ductal histological subtype, absence of lymphovascular invasion and the size of SLN metastasis were identified as significant independent factors associated with a higher FNR.

Conclusions

FNRin our institution is acceptable when compared to other large centres. Failure to detect metastasis in frozen section in more than half of our patients was due to ITCs and micrometastasis.
Republished: Monotherapy with stenting in subarachnoid hemorrhage (SAH) after middle cerebral artery dissection
Authors: Puri Ajit S , Gounis Matthew J , Massari Francesco , Howk Mary , Weaver John , Wakhloo Ajay K
Published: April 2015

Isolated middle cerebral artery dissection is a rare clinical entity, with descriptions limited to a few case reports and case series. Symptomatic dissection in the anterior circulation can present as an ischemic stroke in a young population; however, it is rarely associated with subarachnoid hemorrhage. We describe a young patient who presented with acute headache from a subarachnoid hemorrhage that was ultimately determined to be due to a vascular dissection in the middle cerebral artery. The initial angiogram showed vascular irregularities in this area with stenosis. Repeat imaging 4 days after presentation identified a pseudoaneurysm proximal to the stenosis. The patient was successfully treated with a self-expanding nitinol stent and followed up with serial angiography during postoperative recovery in the hospital; additional angiograms were performed approximately 1 and 6 months after treatment. Serial angiograms demonstrated incremental healing of the dissection. The patient was discharged and remains neurologically intact at the 6-month follow-up.
Glucocorticoid-induced osteoporosis
Authors: Briot Karine , Roux Christian
Published: April 2015

Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the first cause in young people. Bone loss and increased rate of fractures occur early after the initiation of corticosteroid therapy, and are then related to dosage and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurements, as it is also related to alteration of bone quality and increased risk of falls. In patients with rheumatoid arthritis, a treat-to-target strategy focusing on low disease activity including through the use of low dose of prednisone, is a key determinant of bone loss prevention. Bone loss magnitude is variable and there is no clearly identified predictor of the individual risk of fracture. Prevention or treatment of osteoporosis should be considered in all patients who receive prednisone. Bisphosphonates and the anabolic agent parathyroid hormone (1–34) have shown their efficacy in the treatment of corticosteroid-induced osteoporosis. Recent international guidelines are available and should guide management of corticosteroid-induced osteoporosis, which remains under-diagnosed and under-treated. Duration of antiosteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the underlying inflammation evolution.
First‐year student diary
Authors: Perrett Rosie
Published: April 2015

Spring is finally here: the sun is shining and generally everyone seems a lot perkier says Rosie Perrett, first‐year student at Liverpool. Whether that's related to the Easter break is not clear as the past month has been as busy as ever.
Complexities of Some Problems Related to Synchronizing, Non-Synchronizing and Monotonic Automata
Authors: Türker Uraz Cengiz , Yenigün Hüsnü
Published: April 2015

In this study, we first introduce several problems related to finding reset words for deterministic finite automata, and present motivations for these problems for practical applications in areas such as robotics and bio-engineering. We then analyse computational complexities of these problems.

Second, we consider monotonic and partially specified automata. Monotonicity is known to be a feature simplyfing the synchronizability problems. On the other hand for partially specified automata, synchronizability problems are known to be harder than the completely specified automata. We investigate the complexity of some synchronizability problems for automata that are both monotonic and partially specified. We show that checking the existence, computing one, and computing a shortest reset word for a monotonic partially specified automaton is NP-hard.

We also show that finding a reset word that synchronizes 𝓚 number of states (or maximum number of states) of a given monotonic non-synchronizable automaton to a given set of states is NP-hard.
Enhancement of transport properties introduced complex defect in (6, 3) carbon nanotubes
Authors: Cheng Cai-Ping , Hu Hui-Fang , Zhang Zhao-Jin , Wang Xiaowei , Chen Ying , Liu Quanhui , Peng Ping
Published: April 2015

By applying density functional theory (DFT) combined with nonequilibrium Green's function method, we have investigated the electronic structures and quantum transport properties of (6, 3) spiral chiral single-walled carbon nanotubes (SCSWCNTs) in the presence of carboxyl ( COOH )-containing defect complexes. COOH - B - MV complex defect in (6, 3) single-walled carbon nanotubes (SWCNT) was energetically favorable than COOH - B - SW and COOH - B - Per complexes. Our calculated results proved that the complex partially improved the transport properties of (6, 3) SWCNTs with COOH - B - MV complex, but reduced the efficient transmission channels of (6, 3) SWCNTs with COOH - B - SW and COOH - B - Per complexes. It is anticipated that metallic-like (6, 3) SWCNT with COOH -containing complex defects can exhibit large range variations in transport behaviors, which are strongly dependent on the coupling between COOH group and B - MV complex defect. These tremendous properties suggest potential application of COOH -containing B -doped complexes in CNTs-based nanoelectronic devices.
Subharmonic solutions of the prescribed curvature equation
Authors: Corsato Chiara , Omari Pierpaolo , Zanolin Fabio
Published: April 2015

We study the existence of subharmonic solutions of the prescribed curvature equation [Formula: see text] According to the behavior at zero, or at infinity, of the prescribed curvature [Formula: see text], we prove the existence of arbitrarily small classical subharmonic solutions, or bounded variation subharmonic solutions with arbitrarily large oscillations.
CERAMIC THIN FILMS REALIZED BY MEANS OF PULSED PLASMA DEPOSITION TECHNIQUE: APPLICATIONS FOR ORTHOPEDICS
Authors: BIANCHI MICHELE , LOPOMO NICOLA , BOI MARCO , GAMBARDELLA ALESSANDRO , MARCHIORI GREGORIO , BERNI MATTEO , PAVAN PIERO , MARCACCI MAURILIO , RUSSO ALESSANDRO
Published: April 2015

Joint prosthesis are usually subjected to several failing mechanisms, including wear of the ultra-high molecular weight polyethylene (UHMWPE) insert. The main goal of this study was to assess the possibility to improve the tribological properties of titanium component by depositing zirconia thin films on its surface by pulsed plasma deposition (PPD) method. Zirconia-coated titanium spheres were tested against UHMWPE disks, both in dry and wet conditions. Zirconia films exhibited a homogenous sub-micrometric grain size distribution and low roughness. Interestingly, zirconia-coated titanium spheres showed lower wear rate of the UHMWPE component, compared to uncoated titanium spheres, supporting the feasibility of the proposed approach.
TOTAL OSSICULAR REPLACEMENT PROSTHESIS OF THE MIDDLE EAR: A BIOMECHANICAL ANALYSIS
Authors: GENTIL FERNANDA , MARQUES MARCO , PARENTE MARCO , MARTINS PEDRO , SANTOS CARLA , JORGE RENATO NATAL
Published: April 2015

The main goal of the present study is to analyze and characterize the behavior of the middle ear, when a total ossicular replacement prosthesis (TORP) is used in the ossicular chain, in order to troubleshoot conductive hearing loss. Using a finite element model (FEM), a dynamic study of the middle ear was made. The displacement values were obtained at the umbo and stapes footplate, for a sound pressure level of 80 dB sound pressure level (SPL) applied at the tympanic membrane, when a cartilage in membrane-prosthesis interface of different diameters and thicknesses was used. The results were compared with the healthy middle ear model. The usage of this model aims to achieve a set of techniques that promotes the best possible performance of prosthesis in the middle ear. The present study allows to conclude that the rehabilitation of the middle ear with TORP can lead to the best results when used with 4 mm diameter cartilages, with a thin thickness of 0.3 mm.
DESIGN OF A NOVEL FORCE PLATFORM FOR GAIT ANALYSIS: FEM ANALYSIS
Authors: TAMBURINI PAOLA , STAGNI RITA , CAPPELLO ANGELO
Published: April 2015

The gait analysis of subjects with short and non-uniform gait is difficult using the common commercial force platforms. The present work consists in the design, based on finite element method (FEM) analysis, of a force platform of two different dimensions (0.40 × 0.40 m and 0.80 × 0.40 m) considering static and dynamic simulation of their behavior. The aim of this project is to improve, with a simple, low cost and flexible structure, the instrumentation available for the gait analysis of children, neurologic patients and in general the most common clinical cases. The applicability of gait analysis to children, neurologic patients ECC can be improved by the flexibility of force platforms without losing the performance provided by traditional force platforms (e.g., for postural analysis).
STENOSIS EFFECTS ON THE FLUID MECHANICS OF THE COMMON CAROTID ARTERY BIFURCATION FOR UNSTEADY FLOWS
Authors: ANTONOVA N. , XU D. , VELCHEVA I. , KALIVIOTIS E. , TOSHEVA P.
Published: April 2015

The time-varying blood flow in the common carotid artery (CCA) bifurcation is numerically studied on the basis of Navier-Stokes equations for four different cases, including cases with stenoses at different sites in the vicinity of the bifurcation. The cases studied were: (a) without stenoses, (b) with one stenosis upstream the bifurcation, (c) with two opposite stenoses upstream the bifurcation and (d) with an additional stenosis on the apex of the bifurcation. The mesh was generated via a geometry reconstruction and imported into a computational fluid dynamics (CFD) solver. The numerical results of the blood flow in the CCA bifurcation gave a detailed picture of the axial velocity and presented as velocity and vorticity magnitudes. More specifically, it was observed that the appearance of stenotic regions upstream the bifurcation affect both the velocity and vorticity characteristics, whereas a stenoses on the apex of the bifurcation seems to have a small effect on the vorticity characteristics downstream the flow.
ASSESSMENT OF MITRAL REGURGITATION THROUGH DOPPLER ECHOCARDIOGRAPHY: FEASIBILITY, PITFALLS AND DIAGNOSTIC ADVANTAGES
Authors: BARBARESI ELENA , CANNIZZO MARINA , SCHINZARI MATTEO , LONGHI SIMONE , MASETTI MARCO , MINGARDI FRANCESCA , GRIGIONI FRANCESCO , RAPEZZI CLAUDIO , RUSSO ANTONIO
Published: April 2015

Background: Echodoppler quantification of mitral regurgitation (MR) is still controversial, in particular little is known about correlation between quantitative and semi-quantitative methods. Methods and Results: 95 patients (pts) aged 58 +/- 13 years, 56% male, with at least moderate organic MR were enrolled in the period between Oct 2006 and Nov 2014. The etiology of MR was flail of MV leaflet. Regurgitant volume (RV) and effective regurgitant orifice (ERO) quantified by PISA (RV 56 ± 17 mL, ERO 0.32 ± 0.09 cm2), Doppler (RV 58 ± 17 mL, ERO 0.34 ± 0.12 cm2) and Volumetric (RV 48 ± 17 mL, ERO 0.27 ± 0.1 cm2) methods, were similar, particularly by quantitative Doppler and PISA (R2 0.89, p < 0.001). By semiquantitative methods jet area 4C was 9.1 ± 4.4 cm2, jet area/left atrium (LA) area 41 ± 20%, vena contracta (VC) was 5 ± 4.2 mm; pulmonary vein (PV) systolic flow reversal was present in 44% of patients. Only VC width among semiquantitative methods showed a sufficient correlation with RV (R2 0.52, p < 0.001), weaker with ERO (R2 0.46, p < 0.001). Conclusion: MR should be always evaluated by quantitative methods, particularly doppler and PISA RV and ERO, which showed the best correlation. Among semiquantitative methods only VC width represents a good option to RV or ERO evaluation by quantitative methods.
MODELING GLIOBLASTOMA RESPONSE TO RADIOTHERAPY BY COMBINING A TWO-COMPARTMENT KINETIC MODEL AND MULTIPARAMETRIC NMR DATA
Authors: CORAZZA ANDREA , MANCO LUIGI , SGHEDONI ROBERTO , IORI MAURO , NITROSI ANDREA , BERTOLINI MARCO , TURRA ALESSANDRO , FAINARDI ENRICO , GIAMPIERI ENRICO , REMONDINI DANIEL , CASTELLANI GASTONE
Published: April 2015

Glioblastoma are the most common and malignant primary brain tumor, and actual treatments consist of surgery (when possible), radiotherapy and chemotherapy. Recent discoveries in biology revealed the important role of radioresistant cancer stem cell in the tumor proliferation and also showed that differentiated tumor cells can revert to a stem-like state because of radiation. These discoveries can be used to create mathematical models to study and plan new optimized radiotherapy schedules. In literature, some models have already been developed on murine population. The aim of this study was to reproduce these models, to perform a sensitivity analysis to find the most sensitive parameters and to adapt them to standard schedules used with human patients. We found that the most sensitive parameters are those involving tumor cell proliferation, radio-sensibility and quiescence times of both stem and tumor cells.
CARBON DIOXIDE ANGIOGRAPHY: SIMULATION OF OPERATIVE CONDITIONS FOR DIAGNOSTIC IMAGE OPTIMIZATION
Authors: BIANCHINI DAVID , ROSSI PIER LUCA , FELICIANI GIACOMO , LOMBI ALESSANDRO , CORAZZA IVAN , ZANNOLI ROMANO
Published: April 2015

Carbon dioxide angiography is based on the visualization (i.e., the radiographic contrast) of gas bubbles injected in blood vessels. By using an experimental X-ray bench, the energy response of a flat panel detector has been measured (Varian CB4030) and, with a dedicated phantom and a software simulation, the image contrast of vessels is injected with Iodine and CO 2. Moreover, the dynamical behavior of a moving gas bubble has been studied with the software simulator. The results show that the contrast generated by carbon dioxide is about one fourth of that obtained with iodine, demonstrating that CO 2 angiography should use different radiological settings with respect to iodine angiography. In particular, a kVp increase has a lower reduction of contrast-to-noise-ratio (CNR) with carbon dioxide than with iodinated contrast medium (CM), suggesting possible technological improvements both on radiological emission and image enhancement methods.
ULTRASONIC WAVE IS DETERMINED BY FABRIC TENSOR: AN APPLICATION TO CALCANEUS
Authors: YOON YOUNG JUNE
Published: April 2015

The fabric tensor is a good measure for determining the mechanical properties of cancellous bone. Ultrasound is one method used to measure these mechanical properties. Ultrasound-generated speed of sound (SOS) measures the mechanical properties of cancellous bone. Thus, in this paper, we started with the fact that the fast wave in poroelastic theory is identical to the bulk wave velocity. We then formulate the equation for the fast wave in terms of fabric tensor for the calcaneus. The formulation in this paper is simpler than previously published results and will be easy to use in future experiments.
RESTORATION OF THE SEAL FUNCTION OF THE ACETABULAR LABRUM: IN VITRO STUDY
Authors: SIGNORELLI CECILIA , LOPOMO NICOLA , COLLE FRANCESCA , BONTEMPI MARCO , VISANI ANDREA , ZAFFAGNINI STEFANO , MARCACCI MAURILIO , SAFRAN MARC R.
Published: April 2015

An effective acetabular labrum is able to create a seal between the peripheral and central compartment of the hip joint. The goal of this study was to determine the effects of labral tears, repair and labrectromy on labrum function by using a navigation system and a load cell. The hip joint center displacement (mm) and the distraction load (N) was measured in 8 cadaveric hips during distraction maneuvers. These measurements were repeated after creating an anterolateral tear, cercalge repair, vertical mattress repair and labrectomy, respectively. Compared to the intact condition, 3% and 15% higher displacement was provoked during distraction test after labral–chondral separation and labrectomy. Moreover, significantly less force was required to distract the femur after cercalge repair (25%), vertical mattress repair (22%) and labrectomy (40%). A breach of the integrity of labral function was shown to lead to decreased femoral stability relative to the acetabulum during extreme ranges of motion.
A RAPID AND AUTOMATED METHOD TO DETERMINE APPROPRIATE EXERCISE PARAMETERS FOR TAILORED SUBSTRATE CONSUMPTION DURING AEROBIC EXERCISE
Authors: VITTORI L. N. , MANNERS D. N. , BELLI G. , CORAZZA I. , MAIETTA LATESSA P.
Published: April 2015

The growing prevalence of obesity and metabolic disorders such as type II diabetes, is associated with reduced exercise and maximal fat oxidation rate (Fatmax). The aim of this study was to verify the reliability of a new test protocol (Fatmaxwork) using the INCA software package. Twenty four sedentary subjects was enrolled and performed the following tests using a VO2000 metabolimeter: (1) An incremental test of 20 min to determine the individual Fatmax and maximum rate of fat oxidation (MFO) with new Fatmaxwork test; (2) a constant load test of 60 min. For our subjects, the average fat zone was estimated by INCA at 54.2 ± 4.9% max HR, RER 0.86 ± 0.09, 130 ± 64 W. The results from the constant load test differed by 0.01 ± 1.92 for respiratory gas exchange rate (RER) and -0.22 ± 1.92% for heart rate (HR). This study showed that the Fatmaxwork test can be used to predict Fatmax in untrained overweight subjects and INCA is a reliable and accurate software package.