bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy and associated events in women receiving enzyme replacement therapy for late‐onset glycogen storage disease type II (Pompe disease)
Authors: Rohman Philippa J. , Scott Elaine , Richfield Linda , Ramaswami Uma , Hughes Derralynn A.
Published: July 2016

Aim

Glycogen storage disease type II (GSD II or Pompe disease; OMIM; 232 300) is a rare autosomal recessive lysosomal storage disorder resulting from deficiency of α‐glucosidase and accumulation of glycogen in muscle. Clinical symptoms include weakness of skeletal and respiratory muscles and, in infants, cardiomyopathy. Patients with GSD II receive infusions of recombinant α‐glucosidase (enzyme replacement therapy; ERT), which slow the progression of the disease. ERT is given to male and female patients of all ages but as yet little is documented on the effects of continuing ERT during pregnancy. The aim of this case series was therefore to ascertain the pregnancy outcomes of women with GSD II on ERT and to describe adverse events associated with pregnancy, delivery and therapy.

Methods

The medical records of eight women attending the Royal Free Hospital Lysosomal Storage Disorders Unit were reviewed. Four of the eight women had seven pregnancies over a period of 8 years.

Results

In this series GSD II was associated with interventional deliveries but normal neonates. Cessation of ERT in early pregnancy resulted in deterioration of maternal symptoms and emergence of allergic reactions on restarting ERT.

Conclusion

Individualized care plans are required to ensure the best neonatal and maternal outcomes. Consideration should be given to the potential benefits to mother and fetus of continuing ERT during pregnancy.
Graphical Representation and Industrial Design Law Harmonisation
Authors: Kapyrina Natalia
Published: July 2016

Elément essentiel de la demande menant à la délivrance du titre de propriété sur l'apparence d'un produit, l'étude de la représentation graphique permet de s'engager dans plusieurs pistes de réflexion pour avancer sur la question de l'harmonisation du régime international de protection de la forme des produits qui nous entourent. Sans chercher à combler le hiatus entre les dessins et modèles industriels et les œuvres des arts appliqués, nous explorons les mécanismes qui permettront à l'avenir d'alléger les disparités dans la pratique du droit des dessins et modèles, augmentant ainsi son attractivité.

The graphical representation of a design is the central element of any registration procedure leading to an exclusive right to the appearance of a product. Acknowledging that, and concentrating specifically on this formal aspect, helps to advance the complex issue of international design protection harmonisation. Shifting from the search for somehow bridging the gap between industrial designs and works of applied art, we endeavour to explore the mechanisms that shall permit alleviating discrepancies in the practice of sui generis design protections, adding attractiveness to this IP title.
Lactulose reduces bacterial DNA translocation, which worsens neurocognitive shape in cirrhotic patients with minimal hepatic encephalopathy
Authors: Moratalla Alba , Ampuero Javier , Bellot Pablo , Gallego‐Durán Rocío , Zapater Pedro , Roger Manuela , Figueruela Blanca , Martínez‐Moreno Belén , González‐Navajas José M. , Such José , Romero‐Gómez Manuel , Francés Rubén
Published: July 2016

Background & Aims

Minimal hepatic encephalopathy is associated with poor prognosis and mortality in patients with cirrhosis. We aimed at investigating whether bacterial‐DNA translocation affects hyperammonaemia and neurocognitive scores in patients with mHE according to the use of lactulose.

Methods

Observational study including 72 mHE cirrhotic patients, as defined by a psychometric hepatic encephalopathy score (PHES)<−4 and/or a critical flicker frequency (CFF)<39 Hz. Bacterial‐DNA, serum ammonia, pro‐inflammatory cytokines and nitric oxide levels were evaluated. A second cohort of 40 lactulose‐untreated patients were evaluated before and 6–month after lactulose administration (30–60 mL/d).

Results

In the first cohort, bacterial‐DNA rate was significantly higher in patients without lactulose (39% vs 23%, P=.03). Serum ammonia and inflammatory markers were significantly increased in patients with bacterial‐DNA, regardless the use of lactulose, and correlated with the amount of amplified bacterial‐DNA. Neurocognitive scores were significantly worse in bacterial‐DNA positive vs negative patients (PHES −7.6±1.1 vs −5.5±1.0; CFF 32.5±2.6 vs 36.2±2.8, P=.01). Lactulose was associated with improved neurocognitive scores in patients without bacterial‐DNA. Serum ammonia levels inversely correlated with neurocognitive scores in patients with bacterial‐DNA (PHES r=−.84; CFF r=−.72, P=.001). In the second cohort, lactulose reduced bacterial‐DNA translocation (36%–16%, P=.02). Neurocognitive scores were significantly improved in bacterial‐DNA positive patients who cleared bacterial‐DNA during the period on lactulose. Serum ammonia levels correlated with both neurocognitive scores in patients with bacterial‐DNA, either before or after lactulose.

Conclusion

Bacterial‐DNA translocation worsens neurocognitive scores in mHE patients and it is reduced by lactulose, enhancing the relevance of controlling bacterial antigen translocation in these patients.
Bioerosion by the sea urchin Diadema mexicanum along Eastern Tropical Pacific coral reefs
Authors: Alvarado Juan José , Cortés Jorge , Guzman Hector , Reyes‐Bonilla Héctor
Published: July 2016

Bioerosion is a natural process in coral reefs. It is fundamental to the health of these ecosystems. In the Eastern Tropical Pacific (ETP) coral reefs, the most important bioeroders are sponges, bivalves, sea urchins and the fish Arothron meleagris. In the 1980s, El Niño caused high coral mortality and an increase in macroalgal growth. As a result, greater sea urchin bioerosion occurred. This weakened the reef framework. Considering the high vulnerability of the ETP coral reefs, the goal of this study was to determine the current bioerosion impact of the sea urchin Diadema mexicanum along the western coasts of Mexico, El Salvador, Costa Rica and Panamá. The balance between coral bioaccretion and sea urchin bioerosion was also calculated. Between 2009 and 2010, in 12 coral reefs localities, D. mexicanum density, bottom cover and rugosity were quantified along band transects. The daily bioerosion rate was obtained from the amount of carbonates evacuated by sea urchins per unit time. The rate of coral accretion was calculated by multiplying the coral growth rate of the dominant genus by the density of their skeleton and by their specific coral cover. The localities were dissimilar (R = 0.765, P < 0.001) in terms of live coral cover, crustose calcareous algae, turf cover, rugosity index, and density and size of D. mexicanum. At all sites, with the exception of Bahía Culebra (Costa Rica), coral bioerosion was less than coral bioaccretion. Diadema mexicanum plays a dominant role in the balance of carbonates in the ETP, but this depends on reef condition (protection, overfishing, eutrophication) and so the impacts can be either positive or negative.
Surgery Combined with Radiotherapy to Treat Spinal Tumors: A Review of Published Reports
Authors: Bian Chong , Chen Nong , Li Xi‐lei , Zhou Xiao‐gang , Lin Hong , Jiang Li‐bo , Liu Wang‐mi , Chen Qian , Dong Jian
Published: July 2016

Spinal tumors result in high morbidity and a high rate of lower limb paralysis. Both surgical therapy and radiation therapy (RT) are used to treat spinal tumors; however, how best to combine these two therapies to maximize the benefits and minimize the risks is still being debated. It is also difficult to decide the optimal timing, course and dose of RT, especially in pregnant women and children. The aim of this review is to assist surgeons who are dealing with spinal tumors by providing comprehensive information about advanced techniques for administering RT with greater precision and safety, and about the impact of various ways of combining surgery and RT on therapeutic outcomes. We here review published reports about treating spinal tumors with a combination of these two forms of therapy and attempt to draw appropriate conclusions concerning selection of optimal treatment protocols. Our conclusion is that postoperative radiotherapy, especially with high‐precision, low‐dose and multiple fractions, and brachytherapy are promising therapies to combined with surgery.
Characterization of MicroRNA Expression Profiles in Patients with Giant Cell Tumor
Authors: Qin Shu , He Neng‐bin , Yan Hong‐liang , Dong Yang
Published: July 2016

Objective

Giant cell tumors of bone (GCTs) are bone destructive neoplasms, the bone resorption being mediated by osteoclasts. Given that microRNAs are crucially involved in tumorigenesis and the modulation of cell fate and behavior, they are promising candidates for regulation of osteoclastogenesis. However, no reliable miRNAs profile for GCT is available. Our study aimed to evaluate osteoclastogenesis‐related miRNA expression in GCTs of Chinese patients.

Methods

From January 2013 to December 2014, 11 patients with GCTs were treated in our department and grouped into a GCT group. A control group comprising four patients with benign tumors of the iliac bone was established. The diagnoses were initially established by imaging examinations and intraoperative frozen sections and later confirmed by standard histologic examination. The GCT group (five male and six female patients) were aged from 17 to 61 years (mean, 32.9 years; SD, 12.8 years). Six patients with GCT underwent intralesional curettage surgery and the other five wide resection. According to Campanacci grading, four patients had Grade I tumors, three Grade II, and three Grade III. The average age of the control group was 28.75 years (SD, 14.24 years); all of them were diagnosed as having benign tumors and underwent iliac grafting. The morphology of the excised tissue was evaluated by examining standardized hematoxylin and eosin (HE) stained paraffin‐embedded samples. In all, three osteoclastogenesis‐related RNAs and 20 microRNAs (miRNAs) were extracted from the patients. The strength of expression was assessed by quantitative reverse transcription polymerase chain reaction (PCR
) and the results assessed by a Student's t test.

Results

Examination of HE stained sections revealed that the higher the Campanacci grade, the more numerous and bigger the osteoclasts (P < 0.05). PCR results indicated large amounts of osteoclast‐related mRNA (cathepsin K, tartrate‐resistant acid phosphatase and matrix metalloproteinase9) in GCTs (P < 0.05). Expression of six miRNAs was significantly weaker in the GCT than the control group (P < 0.05). The expression of has‐mir‐16‐5p and has‐let‐7a‐5p was correlated with Campanacci grade in the GCT patients (P = 0.009 and 0.034, respectively). The expression of these two miRNAs may indicate severity of bone destruction.

Conclusion

Overall, the clinical utility of six novel miRNA markers for GCTs was demonstrated. Of these, strength of expression of hsa‐mir‐16‐5p and hsa‐let‐7a‐5p may indicate the grade of bone resorption.
Open Surgery for Osteoid Osteoma with Three Dimensional C‐arm Scan under the Guidance of Computer Navigation
Authors: Lin Nong , Ye Zhao‐ming , Qu Hao , Yan Xiao‐bo , Pan Wei‐bo , Huang Xin , Liu Meng
Published: July 2016

Objective

To evaluate the clinical outcomes of open surgery for osteoid osteoma with three‐dimensional (3‐D) C‐arm scan under the guidance of computer navigation.

Methods

The clinical data of 14 patients who had undergone 3‐D C‐arm scan under the guidance of computer navigation during open surgery for osteoid osteoma from March 2012 to June 2015 were analyzed retrospectively. There were nine male and five female subjects aged from 9 to 55 years (mean, 26 years). Eight of the tumors were located in the femur, four in the tibia, one in the humerus and one in the scapula. Preoperative pain visual analogue scale (VAS) scores ranged from 2 to 6 (mean ± SD, 4.7 ± 1.1). Conventional surgical approaches were used to expose the tumor surfaces depending on their locations. Involved regions were scanned by 3‐D C‐arm fluoroscopy during the procedure and then the tumors were accurately located and their niduses removed under the guidance of computer navigation. Afterwards, repeat 3‐D C‐arm scans of the surgical region were performed to confirm tumor eradication. None of the patients received postoperative intravenous analgesia. Eight patients received oral non‐steroidal anti‐inflammatory drugs on the day of surgery, these drugs being discontinued on the second postoperative day. Postoperative pathological diagnoses were recorded. At the follow‐up visits, imaging and VAS scores were obtained to evaluate the therapeutic effect and any evidence of recurrence.

Results

All the patients successfully underwent computer navigation‐guided surgery. The duration of surgery ranged from 60 to 135 min (mean, 94 min) and the amount of bleeding from 50 to 150 mL (mean, 80 mL). None of the patients needed bone grafting or internal fixation. No complications were seen. All patients were followed up for 4 to 36 months (mean, 16 months). Postoperative pathological diagnoses of osteoid osteoma were made in 12 patients; thus, the rate of pathologically confirmed diagnosis was 86%. VAS scores decrease to an average of 1.4 ± 0.6 3 days after surgery and were zero for all patients 4 months after surgery. No tumor recurrence was found by X‐ray or CT scan examination during follow‐up.

Conclusions

The niduses of osteoid osteomas can be eradicated by open surgery with 3‐D C‐arm scan under the guidance of computer navigation with minimal damage to bone structure and a high rate of pathologically confirmed diagnoses.
Advances in Bone‐targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma
Authors: Li Cheng‐jun , Liu Xiao‐zhou , Zhang Lei , Chen Long‐bang , Shi Xin , Wu Su‐jia , Zhao Jian‐ning
Published: July 2016

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone‐targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone‐targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi‐pathway targets is an important research aspect of designing new bone‐targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone‐targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma.
Delay in Diagnosis and Its Effect on Clinical Outcome in High‐grade Sarcoma of Bone: A Referral Oncological Centre Study
Authors: Goedhart Louren M , Gerbers Jasper G , Ploegmakers Joris J W , Jutte Paul C
Published: July 2016

Objective

To investigate delay in diagnosis by both patients and doctors, and to evaluate its effect on outcomes of high‐grade sarcoma of bone in a single‐referral oncological center.

Methods

Fifty‐four patients with osteosarcoma, 29 with Ewing sarcoma and 19 with chondrosarcoma were enrolled in this retrospective study. Delay in diagnosis was defined as the period between initial clinical symptoms and histopathological diagnosis at our center. The delays were categorized as patient‐ or doctor‐related. Short total delays were defined as <4 months; prolonged delays >4 months were assumed to have prognostic relevance.

Results

Total delay in diagnosis was 688.0 days in patients with chondrosarcoma, which is significantly longer than the 163.3 days for osteosarcoma (P < 0.01) and 160.2 days for Ewing sarcoma (P < 0.01). Most doctor‐related delays were at the pre‐hospital stage, occurring at the general practitioner (GP)'s office. However, prolonged total delays (≥4 months) did not result in lower survival rates. Five‐year‐overall survival rates were 67.0% for osteosarcoma, 49.0% for Ewing sarcoma and 60.9% for chondrosarcoma. Survival was significantly lower for patients with metastatic disease for all three types of sarcoma.

Conclusion

Prolonged delay in diagnosis does not result in lower survival. Metastatic disease has a pronounced effect on survival. Aggressive tumor behavior results in shorter delays. Minimizing GP‐related delays could be achieved by adopting a lower threshold for obtaining plain radiographs at the pre‐hospital stage.
Biological Reconstruction in Bone Sarcomas: Lessons from Three Decades of Experience
Authors: San‐Julian Mikel , Vazquez‐Garcia Blanca
Published: July 2016

Objective

To review research on all patients treated by biological reconstruction after resection of bone sarcomas between 1987 and 2015 at our hospital.

Methods

One thousand one hundred and sixty‐seven cortical allografts and 166 cortical autografts were retrospectively analyzed. Radiological studies had been performed to determine the timing of consolidation of the grafts at both the metaphyseal and diaphyseal osteotomies. A prospective isotopic study with 99 Tc was done in order to evaluate the revascularization of allografts. Histological, immunohistochemistry and fluorescence techniques were used on retrieved allografts to evaluate their integration. Complications, functional results and possible relationships with human leukocyte antigen (HLA) compatibility, were also reviewed.

Results

The mean age of these patients with bone sarcomas was 19 years (range, 3–69 years). The mean length of cortical allografts was 19.5 cm (range, 4–42 cm) and of autografts 8 cm (range, 6–15 cm). The mean consolidation time of diaphyseal osteotomies was 16 months. The mean time to consolidation was 5 months for vascularized autografts and 12 months for non‐vascularized grafts. New bone formation was observed at the host bone–allograft junction. Complications included non‐union (16.2%), fractures (8.2%) and infections (11.8%). The incidence of complications was higher in the non‐compatible group; however, no significant relationship was found between HLA compatibility (or lack thereof) and the occurrence of complications.

Conclusions

Allografts are a good option for reconstruction after removal of larger tumors. It is necessary to take into account the mechanisms of incorporation and the measures that can be taken to reduce complications.
Musculoskeletal Hydatid Cysts Resembling Tumors: A Report of Five Cases
Authors: Toğral Güray , Arıkan Şefik M , Ekiz Timur , Kekeç Ahmet F , Ekşioğlu Mehmet F
Published: July 2016

Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce. This paper presented 5 patients (3 males, 2 females) with a mean age of 41.6 years with tumor‐like lesions of HC. Three of them had left ilium and acetabulum involvement, one involved left femur, and one involved left thigh muscle compartments. Pain was the main symptom and was seen in all patients. Clinical examination, radiologic evaluation, and histologic analysis were performed for diagnosis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, hip arthrodesis, reconstruction using hemipelvic replantation with femoral prosthesis and distal femur endoprosthetic replacement. After surgery, the operation region was washed by 20% hypertonic saline, and debridement was performed carefully without contamination. All patients received albendazole treatment. Cases were followed up 1 to 9 years for the recurrence. Walking difficulty and pain were the main symptoms during the follow‐up. One patient was symptom‐free. A reoccurrence in the perioperative soft tissue was detected in only one patient and control visits with antihelmintic treatment were recommended. We would like to emphasize that HC should be kept in mind for the differential diagnosis of the cystic or tumoral lesions of the musculoskeletal system, particularly in the endemic regions. Prompt diagnosis is of paramount importance for preventing destruction and complications.
Too Close for Comfort: Does the Intensity of Municipal Advisor and Underwriter Relationship Impact Borrowing Costs?
Authors: Moldogaziev Tima T. , Luby Martin J.
Published: July 2016

This research explores the intensity of the relationship between municipal advisors and underwriters, as well as their quality and location, to assess the resulting impact on borrowing costs for negotiated debt. The findings from this research have practical policy implications related to the proper composition of a local government's debt financing team. In addition, the empirical findings shed light on central aspects in debt management networks as determined by the round‐trip transaction (RTT) theory, which point at new levers that subnational policy makers may use to gain efficiencies when accessing the municipal debt market.
Public Borrowing for Private Organizations: Costs and Structure of Tax‐Exempt Debt Through Conduit Issuers
Authors: Ely Todd L. , Calabrese Thad D.
Published: July 2016

Conduits are public organizations that issue debt on behalf of third‐party borrowers, both government and private. Additional transaction costs from using conduits offset lower interest costs. We find debt issuance costs 25 percent higher for private organizations than the broader municipal debt market, primarily from fees charged by conduits. Further, existing issuance cost reporting focuses on upfront costs, which fail to capture the significance of annual conduit fees. Also, private borrowers have debt structures that keep more principal outstanding over longer periods of time. Despite additional costs, conduits still provide these private borrowers with substantial interest cost savings.
Addressing Supply–Demand Imbalance: Designing Efficient Remanufacturing Strategies
Authors: Jia Justin , Xu Susan H. , Guide V. Daniel R.
Published: July 2016

The management of remanufacturing inventory system is often challenged by mismatched supply (i.e., returned units, called cores) and demand. Typically, the demand for remanufactured units is high and exceeds the supply early in a product's lifetime, and drops below the supply late in the lifetime. This supply–demand imbalance motivates us to study a switching strategy to facilitate the decision‐making process. This strategy deploys a push mode at the early stage of a product's lifetime, which remanufactures scarce cores to stock to responsively satisfy the high demand, and switches to a pull mode as the product approaches obsolescence to accurately match the low demand with supply. In addition, the strategy further simplifies the decision‐making process by ignoring the impact of leftover cores at the end of each decision period. We show that the optimal policy of the switching strategy possesses a simple, multi‐dimensional base‐stock structure, which aims to remanufacture units from the i best‐quality categories up to the ith state‐independent base‐stock level. An extensive numerical study shows that the switching strategy delivers close‐to‐optimal and robust performance: the strategy only incurs an average profit loss of 1.21% and a maximum of 2.27%, compared with the optimal one. The numerical study also shows when a pure push or pull strategy, a special case of the switching strategy, delivers good performance. The study offers the managerial insight that firms can use simple, easy‐to‐implement strategies to efficiently manage the remanufacturing inventory system.
Public Transfers and Participation Decisions in Botswana's Subsistence Economy
Authors: Seleka Tebogo B. , Lekobane Khaufelo R.
Published: July 2016

Botswana has an extensive set of publicly provided cash and in‐kind food transfers geared at providing a safety net to poor and vulnerable groups. While such programs have improved household welfare, from a theoretical perspective they could have also created work disincentives or welfare dependency among recipient families. This article tackles this issue by modeling the impact of publicly provided cash and in‐kind food transfers on farmer participation decisions in the subsistence crop economy in Botswana, using a probit regression and agricultural census data for 2004. Results show that social pensions have had no impact on farmer participation decisions, most likely because they are too small to influence household behavior. However, government food rations (GFRs) have reduced the probability of farmer participation in subsistence crop production, and, hence, have created work disincentive among recipient subsistence families. Specifically, recipient families of GFRs are 8.1 percentage points less likely to participate in crop production than non‐recipient households.
A Description of Suicides in the Army National Guard During 2007–2014 and Associated Risk Factors
Authors: Griffith James
Published: July 2016

Suicide, due to its increased occurrence in recent years, has been a chief concern of the U.S. military. While there have been many published studies on the topic, conspicuously absent are studies that have included reserve military personnel. To fill this gap, this study reports descriptive statistics of personnel information and events surrounding 706 Army National Guard suicides that had occurred from 2007 through 2014. Comparative personnel information for random samples of nonsuicides for similar years (8 years, 1,000 cases per year) allowed examining factors associated most with suicide. Findings were very similar to those observed in the active duty Army and civilian populations. Primary risk factors for suicide were as follows: age (young), gender (male), and race/ethnicity (White). Most suicides occurred in nonmilitary status (86%) involving personal firearms (72%). Most frequent events surrounding the suicide were as follows: poor military performance (36% of all suicides), parent–family relationship problems (28%), substance abuse (27%), past behavioral health problem (20%), current behavioral health problems (10%), income problems (22%), and full‐time employment problems (18%). Implications of findings for suicide prevention are discussed.
Evidentiality and Raising to Object as A′‐Movement: A Romanian Case Study
Authors: Alboiu Gabriela , Hill Virginia
Published: July 2016

Romanian displays a construction in which the subject of an embedded indicative clause surfaces with accusative form in the matrix clause. This resembles Exceptional Case Marking (ECM) and occurs with matrix verbs of knowledge and perception. We argue that: (i) such derivations arise from Raising to Object (RtoO) across the phasal indicativeCP; (ii) RtoO in Romanian is an instance of A′‐movement with A‐movement effects derived from the v‐related nature of the A′‐Probe; and (iii) the trigger for movement is related to a shift in evidentiality rather than Case requirements.
Long‐lasting extreme anemia during the therapy of acute lymphoblastic leukemia in a Jehovah's Witness patient
Authors: Chojnowski Krzysztof , Janus Agnieszka , Bliźniewska Katarzyna , Robak Marta , Treliński Jacek
Published: July 2016

BACKGROUND

The treatment of patients with acute leukemia, who due to their religious beliefs refuse to accept blood transfusion, is a great challenge for hematologists.

CASE REPORT

We present a case of acute pre‐T‐lymphoblastic leukemia in a Jehovah's Witness who did not accept blood transfusion during chemotherapy. Standard induction and consolidation chemotherapy was used (according to the PALG ALL‐6 regiment).

RESULTS

During consolidation cycles, darbepoietin alfa, intravenous iron, and total parenteral nutrition was administered. Extreme (Hb < 5 g/dL), long‐lasting (41 days) anemia was observed with the lowest Hb concentration amounting to 1.3 g/dL (lasting 7 days).

CONCLUSION

We believe this to be the lowest Hb value observed, particularly one that persisted for such a long period of time and resulted in the patient surviving without consequences. The patient remains in complete remission for more than 2 years after diagnosis.
Impact of the bacteriology of diabetic foot ulcers in limb loss
Authors: Hinojosa Carlos A. , Boyer‐Duck Estefania , Anaya‐Ayala Javier E. , Nunez‐Salgado Ana , Laparra‐Escareno Hugo , Torres‐Machorro Adriana , Lizola Rene
Published: July 2016

Infections in feet of patients with diabetes mellitus is common, complex and costly. The aim of this study to investigate the isolated microorganisms in infected diabetic foot ulcers, and the impact of these infectious agents in limb loss in a tertiary medical center in Mexico City. We conducted a retrospective review in diabetic patients with infected foot ulcers from 1997 to 2014. Diabetic foot was defined according to the World Health Organization (WHO), the bacteriology of wound cultures and the impact of microorganisms in limb loss (major amputation) was studied. Patient's demographics, comorbidities, wound characteristics, and other factors associated in clinical outcomes were determined. A total of 165 subjects with soft tissue infections and/or osteomyelitis and positive cultures were included. One hundred and five (64%) were male, with a mean age of 60 year old +/− 15. One hundred fifty‐nine (96%) had Type 2 diabetes mellitus, 68 (41%) history of peripheral arterial disease (PAD) and 97 (59%) patients had osteomyelitis. In 89 patients (54%), cultures were polymicrobial and one single organism was isolated in 76 cultures (46%). During the follow up, 96 (58%) patients preserved their limbs and 69 (42%) required major amputation (above or below knee). Sixty percent of patients that suffered from limb loss had polymicrobial culture (p = 0.13). Growth of Escherichia coli and Enterococcus faecium (p = 0.03) and E. coli and Morganella morgagnii (p = 0.03) was associated to limb loss. Among monomicrobial cultures, infections associated with Proteous mirabilis had higher rate of progression to limb loss (p = 0.03). PAD was associated to limb loss (p = 0.001). Management of diabetic foot requires a multimodality approach. In this study, in patients that received appropriate antibiotic therapy and optimal surgical management, we observed that history of PAD, polymicrobial and isolated P. mirabilis infections were variables associated with higher rate of limb loss.
Research on the Deposit Insurance Pricing Under the Marketing RMB Interest Rate
Authors: Sun Lingyan , Shi Tianning , Shi Panlu
Published: July 2016

The deposit insurance pricing is the core issue of deposit insurance system, it determines the success or failure of the deposit insurance system in a way. In the current deposit insurance pricing methods, we treat the interest rates as a constant. With the interest rate marketization in China, the deposit insurance pricing methods have also changed accordingly. In this paper, we will give a functional representation of the impact of RMB interest rate marketization on interest rate by fitting the coefficients of the cubic function. Then we will use the data of 2013 to prove it. For the points that do not conform to this rule, we also have some explanations related to the major economic events at that time.
Vibration Suppression of an Underactuated Dynamic System Using Virtual Actuators
Authors: Khoshnood A. M. , Azad I. , Hasani S. M.
Published: July 2016

Sloshing is one of the critical problems in aerospace vehicles with liquid containers. Motion of the liquid in resonance situations can degrade the stability and performance of attitude control systems. Two important characteristics of this time varying phenomenon are sensorless and underactuated properties which lead to difficulty of attitude control system design. In this paper, a new technique based on soft sensor and virtual actuator is used to suppress the effects of fuel sloshing in an aerospace launch vehicle (ALV). For this purpose, a nonlinear dynamic model of the vehicle with mechanical model of the fuel sloshing is considered as a multibody dynamic system. The preliminary attitude control system of the vehicle is extended using the new vibration suppression technique and a numerical simulation of the nonlinear model is carried out. Results of the simulation show that the undesired effects of the fuel sloshing are effectively decreased using the proposed vibration suppression technique.
Inverse Prediction of Temperature Through Time Rescaling of High-Temperature Experimental Data
Authors: Myrick J. A. , Keyhani M. , Frankel J. I.
Published: July 2016

This paper presents experimental data from a two-layer test sample made up of a copper layer and an AISI type 316 stainless steel (SS) layer that was heated with a laser power source. Experiments were conducted to generate high-temperature benchmark data that ranged from room temperature to 820 °C. The concept of time rescaling was employed to account for the dependence of thermal diffusivity on temperature in order to utilize the calibration integral equation method (CIEM). The future time regularization method was used to obtain a stable prediction for the surface temperature. An estimate for the future time regularization parameter was acquired through analysis of the in-depth calibration test thermocouple (TC) response. Results for three test cases consisting of selected pairs of calibration data and reconstruction data (to be predicted) are presented and discussed. Four different values of the future time regularization parameter were employed in the three test cases. The proposed nonlinear (NL) formulation improved the prediction accuracy when compared to the constant properties formulation of the CIEM. It should be emphasized that no knowledge of TC probe depth or TC response properties is required.
Athlete Characteristics and Team Competitive Performance as Moderators for the Relationship Between Coach Transformational Leadership and Athlete Performance
Authors: Bormann Kai C. , Schulte-Coerne Paul , Diebig Mathias , Rowold Jens
Published: July 2016

The goal of this study is to examine the effects of coaches’ transformational leadership on player performance. To advance existing research, we examine (a) effects on individual and team performance and (b) consider joint moderating effects of players’ win orientation and teams’ competitive performance on the leadership– individual performance link. In a three-source sample from German handball teams, we collected data on 336 players and 30 coaches and teams. Results showed positive main effects of transformational leadership’s facet of articulating a vision (AV) on team and individual performance and negative main effects of providing an appropriate model (PAM) on team performance. With regard to moderating effects, AV increased and PAM decreased individual performance when both moderators were low, and intellectual stimulation had a positive effect when both were high. This study expands insights into the potential and limitation of transformational leadership with a strong focus on the role of situational contingencies.
Motivation Mediates the Perfectionism–Burnout Relationship: A Three-Wave Longitudinal Study With Junior Athletes
Authors: Madigan Daniel J. , Stoeber Joachim , Passfield Louis
Published: July 2016

Perfectionism in sports has been shown to predict longitudinal changes in athlete burnout. What mediates these changes over time, however, is still unclear. Adopting a self-determination theory perspective and using a three-wave longitudinal design, the current study examined perfectionistic strivings, perfectionistic concerns, autonomous motivation, controlled motivation, and athlete burnout in 141 junior athletes (mean age = 17.3 years) over 6 months of active training. When multilevel structural equation modeling was employed to test a mediational model, a differential pattern of between- and within-person relationships emerged. Whereas autonomous motivation mediated the negative relationship that perfectionistic strivings had with burnout at the between- and within-person level, controlled motivation mediated the positive relationship that perfectionistic concerns had with burnout at the between-persons level only. The present findings suggest that differences in autonomous and controlled motivation explain why perfectionism predicts changes in athlete burnout over time.
Panel slams plan for human research rules
Authors: Malakoff David
Published: July 2016

National Academies report urges creation of new national commission on ethical studies.
Heartmaker's next step: a ray ‘biohybrid’
Authors: Pennisi Elizabeth
Published: July 2016

Light-controlled cardiac muscle cells guide swimming of raybot.
In Canada, peer-review changes stir outrage
Authors: Kondro Wayne
Published: July 2016

Reforms by nation's lead biomedical funder result in shoddy reviews, critics say.
Hurdling obstacles
Authors: Shell Ellen Ruppel
Published: July 2016

Meet Marcia McNutt, scientist, administrator, editor, and now National Academy of Sciences president.
Aftershocks
Earth-Shattering Events Earthquakes, Nations, and Civilization
Andrew Robinson
Thames and Hudson, 2016. 256 pp.
Authors: D'Amico Sebastiano
Published: July 2016

A far-reaching history explores the cultural, economic, and political effects of earthquakes
Thermally stable single-atom platinum-on-ceria catalysts via atom trapping
Authors: Jones John , Xiong Haifeng , DeLaRiva Andrew T. , Peterson Eric J. , Pham Hien , Challa Sivakumar R. , Qi Gongshin , Oh Se , Wiebenga Michelle H. , Pereira Hernández Xavier Isidro , Wang Yong , Datye Abhaya K.
Published: July 2016

Hot single-atom catalysts

For heterogeneous catalysts made from precious metal nanoparticles adsorbed on metal oxides, high temperatures are the enemy. The metal atoms become mobile and the small particles grow larger, causing a loss in surface area and hence in activity. Jones
et al.
turned this process to their advantage and used these mobile species to create single-atom platinum catalysts. The platinum on alumina supported transfers in air at 800°C to ceria supports to form highly active catalysts with isolated metal cations.

Science
, this issue p.
150
Regulatory Interaction between the Cellular Restriction Factor IFI16 and Viral pp65 (pUL83) Modulates Viral Gene Expression and IFI16 Protein Stability
Authors: Biolatti Matteo , Dell'Oste Valentina , Pautasso Sara , von Einem Jens , Marschall Manfred , Plachter Bodo , Gariglio Marisa , De Andrea Marco , Landolfo Santo
Published: July 2016

A key player in the intrinsic resistance against human cytomegalovirus (HCMV) is the interferon-γ-inducible protein 16 (IFI16), which behaves as a viral DNA sensor in the first hours postinfection and as a repressor of viral gene transcription in the later stages. Previous studies on HCMV replication demonstrated that IFI16 binds to the viral protein kinase pUL97, undergoes phosphorylation, and relocalizes to the cytoplasm of infected cells. In this study, we demonstrate that the tegument protein pp65 (pUL83) recruits IFI16 to the promoter of the UL54 gene and downregulates viral replication, as shown by use of the HCMV mutant v65Stop, which lacks pp65 expression. Interestingly, at late time points of HCMV infection, IFI16 is stabilized by its interaction with pp65, which stood in contrast to IFI16 degradation, observed in herpes simplex virus 1 (HSV-1)-infected cells. Moreover, we found that its translocation to the cytoplasm, in addition to pUL97, strictly depends on pp65, as demonstrated with the HCMV mutant RV-VM1, which expresses a form of pp65 unable to translocate into the cytoplasm. Thus, these data reveal a dual role for pp65: during early infection, it modulates IFI16 activity at the promoter of immediate-early and early genes; subsequently, it delocalizes IFI16 from the nucleus into the cytoplasm, thereby stabilizing and protecting it from degradation. Overall, these data identify a novel activity of the pp65/IFI16 interactome involved in the regulation of UL54 gene expression and IFI16 stability during early and late phases of HCMV replication.

IMPORTANCE
The DNA sensor IFI16, a member of the PYHIN proteins, restricts HCMV replication by impairing viral DNA synthesis. Using a mutant virus lacking the tegument protein pp65 (v65Stop), we demonstrate that pp65 recruits IFI16 to the early UL54 gene promoter. As a putative counteraction to its restriction activity, pp65 supports the nucleocytoplasmic export of IFI16, which was demonstrated with the viral mutant RV-VM1 expressing a nuclearly retained pp65. These data reveal a dual role of pp65 in IFI16 regulation: in the early phase of HCMV infection, it contributes to viral evasion from IFI16 restriction activity, while at later time points, it promotes the nuclear delocalization of IFI16, thereby stabilizing and protecting it from degradation. In the present work, we further clarify the mechanisms HCMV relies on to overcome intracellular innate immune restriction and provide new insights into the relevance of DNA-sensing restriction factor IFI16 during HCMV infection.
The Molecular Determinants of Antibody Recognition and Antigenic Drift in the H3 Hemagglutinin of Swine Influenza A Virus
Authors: Abente Eugenio J. , Santos Jefferson , Lewis Nicola S. , Gauger Phillip C. , Stratton Jered , Skepner Eugene , Anderson Tavis K. , Rajao Daniela S. , Perez Daniel R. , Vincent Amy L.
Published: July 2016

Influenza A virus (IAV) of the H3 subtype is an important respiratory pathogen that affects both humans and swine. Vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA) is the primary method used to control disease. However, due to antigenic drift, vaccine strains must be periodically updated. Six of the 7 positions previously identified in human seasonal H3 (positions 145, 155, 156, 158, 159, 189, and 193) were also indicated in swine H3 antigenic evolution. To experimentally test the effect on virus antigenicity of these 7 positions, substitutions were introduced into the HA of an isogenic swine lineage virus. We tested the antigenic effect of these introduced substitutions by using hemagglutination inhibition (HI) data with monovalent swine antisera and antigenic cartography to evaluate the antigenic phenotype of the mutant viruses. Combinations of substitutions within the antigenic motif caused significant changes in antigenicity. One virus mutant that varied at only two positions relative to the wild type had a >4-fold reduction in HI titers compared to homologous antisera. Potential changes in pathogenesis and transmission of the double mutant were evaluated in pigs. Although the double mutant had virus shedding titers and transmissibility comparable to those of the wild type, it caused a significantly lower percentage of lung lesions. Elucidating the antigenic effects of specific amino acid substitutions at these sites in swine H3 IAV has important implications for understanding IAV evolution within pigs as well as for improved vaccine development and control strategies in swine.

IMPORTANCE
A key component of influenza virus evolution is antigenic drift mediated by the accumulation of amino acid substitutions in the hemagglutinin (HA) protein, resulting in escape from prior immunity generated by natural infection or vaccination. Understanding which amino acid positions of the HA contribute to the ability of the virus to avoid prior immunity is important for understanding antigenic evolution and informs vaccine efficacy predictions based on the genetic sequence data from currently circulating strains. Following our previous work characterizing antigenic phenotypes of contemporary wild-type swine H3 influenza viruses, we experimentally validated that substitutions at 6 amino acid positions in the HA protein have major effects on antigenicity. An improved understanding of the antigenic diversity of swine influenza will facilitate a rational approach for selecting more effective vaccine components to control the circulation of influenza in pigs and reduce the potential for zoonotic viruses to emerge.
A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability
Authors: Ding Shilei , Tolbert William D. , Prévost Jérémie , Pacheco Beatriz , Coutu Mathieu , Debbeche Olfa , Xiang Shi-Hua , Pazgier Marzena , Finzi Andrés
Published: July 2016

Previous studies have shown that highly conserved residues in the inner domain of gp120 are required for HIV-1 envelope glycoprotein (Env) transitions to the CD4-bound conformation (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell
37:
656–667, 2010,
http://dx.doi.org/10.1016/j.molcel.2010.02.012
; A. Desormeaux, M. Coutu, H. Medjahed, B. Pacheco, A. Herschhorn, et al., J Virol
87:
2549–2562, 2013,
http://dx.doi.org/10.1128/JVI.03104-12
). Moreover, W69, a highly conserved residue located at the interface between layer 1 and layer 2 of the inner domain, was recently shown to be important for efficient Env recognition by CD4-induced (CD4i) antibodies capable of potent antibody-dependent cellular cytotoxicity (W. D. Tolbert, N. Gohain, M. Veillette, J. P. Chapleau, C. Orlandi, et al., 2016, Structure
24:
697–709,
http://dx.doi.org/10.1016/j.str.2016.03.005
; S. Ding, M. Veillette, M. Coutu, J. Prevost, L. Scharf, et al., 2016, J Virol
90:
2127–2134,
http://dx.doi.org/10.1128/JVI.02779-15
). We evaluated the contribution of the hydrophobicity of W69 to conformational changes of Env by replacing it with a series of residues with aliphatic or aromatic side chains of decreasing chain length. We have found that the hydrophobicity of residue 69 is important for Env processing, CD4 binding, and its transition to the CD4-bound conformation. The most deleterious effect was observed when W69 was replaced with alanine or glycine residues. However, the functions lost due to W69 mutations could be progressively restored with amino acids of increasing aliphatic chain length and fully recovered with residues bearing an aromatic ring. Interestingly, poor CD4 binding of W69A could be fully restored by introducing a compensatory mutation within layer 2 (S115W). Structural studies of HIV-1 gp120 core
e
W69A/S115W mutant bound to the CD4 peptide mimetic M48U1 and Fab of anti-cluster A antibody N60-i3 revealed no perturbations to the overall structure of the double mutant compared to the wild-type protein but identified higher mobility within the interface between layer 1 and layer 2, the bridging sheet region, and the CD4 binding site.

IMPORTANCE
HIV-1 Env transitions to the CD4-bound conformation are required for viral entry. Previous studies identified a highly conserved residue of the inner domain, W69, as being involved in these conformational transitions (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37:656–667, 2010,
http://dx.doi.org/10.1016/j.molcel.2010.02.012
). Here, we show that W69, located at the interface between gp120 and gp41 in the PGT151-bound trimer, plays a critical role in the interprotomer signaling induced by CD4 binding. This new information might be useful in immunogen design.