bluuebunny/crossref_metadata_2025 huggingface dataset:
10. The leasehold estate
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter considers the nature and characteristics of a lease, and the ways in which it is created and brought to an end. It discusses the basic requirements for a lease; the creation of leases; the disposition of leases and reversions; the determination of a lease; determination by discharge of contract; determination by joint tenants; ‘contractualisation’ of leases; the effect on subtenant of determination of head lease; and additional types of lease.
12. Enforcement of leasehold covenants
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter discusses how leasehold covenants are enforced. It considers the effect covenants have on: the original parties to the lease; their successors in title (those who acquire the lease or the reversion from the original tenant or landlord); and subtenants (those who hold a sub-lease granted by the original tenant or his successor in title). The chapter also looks at the breach of covenant before assignment and applies the enforcement of covenants to Trant Way tenancies.
13. Remedies for breach of leasehold covenants
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter discusses the remedies available to one party when the other is in breach of duty. It first deals with general contractual remedies which are available in respect of breach of covenant. It then goes on to consider in more detail some special remedies which are peculiar to leases, and in particular the landlord’s power to forfeit the lease, i.e., to bring it to an end and to evict the tenant.
16. Co-ownership
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter discusses rules relating to the co-ownership of land. It covers joint tenancy; tenancy in common; creating a tenancy in common of the beneficial interest under a trust; the cases of Stack v Dowden and Jones v Kernott; the severance of a joint tenancy; the relationship between co-owners; and the ending of co-ownership.
19. Perpetuities and accumulations
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter provides a brief account of the ‘perpetuities and accumulations’ rules. It discusses future interests; the old perpetuities rules; legislative modifications before 2010; the breadth of the application of old rules; rules about the period for which income can accumulate in a trust; and the Perpetuities and Accumulations Act 2009.
21. Proprietary estoppel
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter examines the doctrine of proprietary estoppel. It discusses the nature of proprietary estoppel; the expectations of future rights; the criteria for proprietary estoppel; essential elements; satisfying the equity; the nature of the equity arising from estoppel; and the relationship between proprietary estoppel and constructive trusts.
24. Mortgages and charges
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter examines the types of mortgages or charges of land and interests in land which may be created. It also considers the rules regarding their administration and their protection against later acquirers of interests in the land. The discussions cover legal mortgages and charges; equitable mortgages; the rights of the mortgagor; the rights of the mortgagee; mortgagee’s remedies; the right of certain third parties to redeem; the liability of mortgagees, receivers, and valuers for fraud or negligence; the end of a mortgage
26. Easements and profits à prendre
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter discusses easements and profits à prendre. It explains the nature of easements and profits; legal and equitable interests; enforcement against acquirer of the servient tenement; acquisition by express grant or reservation; acquisition by implied grant or reservation; acquisition by express grant by virtue of the Law of Property Act 1925, s. 62; acquisition by prescription; remedies which may be used to protect an easement or profit; and the extinguishment of easements and profits.
28. The family home
Authors: MacKenzie Judith-Anne
Published: October 2016

Course-focused and comprehensive, the Textbook on series provide an accessible overview of the key areas on the law curriculum. This chapter brings together some matters about the family home, and provides additional information about certain statutory rights which members of a family may have in respect of their homes, contrasting the rights of married couples and civil partners with the more limited rights of cohabitants. In conclusion, the chapter outlines proposals for reform of the law relating to cohabitants’ rights in the family home.
2. Corporate personality and limited liability
Authors: Dignam Alan , Lowry John
Published: October 2016

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter deals with corporate personality and limited liability, two concepts that form the core of company law. It begins with a short historical background on how the process of corporatisation through charters evolved over time, including the emergence of the use of trust as an instrument to confer many of the privileges of incorporation. It then considers the case Salomon v Salomon & Co (1897) which decided on the legitimacy of small businesses with a corporate form, and offers some other good examples of the consequence of separate personality. The chapter also discusses the rights of members and shareholders with respect to ownership of the corporation, focusing on dispersed shareholdings and close companies.
7. Share capital
Authors: Dignam Alan , Lowry John
Published: October 2016

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter examines how company law governs maintenance of a company’s share capital, with emphasis on the distinction between private and public companies. It also discusses various ways in which shareholders might legally receive funds (‘distributions’) from the company, including issuance of shares and payment of shares in kind (that is, goods, property, or services rather than in cash). The relevance of the nominal value of shares issued to shareholders, the issue of paying dividends to shareholders, and disguised return of capital to shareholders are considered as well. The chapter also examines two other means of returning funds to shareholders, reduction of share capital and redemption or purchase by a company of its own shares, before concluding with an assessment of the prohibition and the exceptions concerning the issue of financial assistance for the acquisition of shares in a public company.
13. Corporate management
Authors: Dignam Alan , Lowry John
Published: October 2016

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter deals with corporate management, focusing on those individuals who are responsible for making key strategic decisions within the company, namely the members of the board of directors. It begins by tracing the emergence of the professional managerial organ, with emphasis on the separation of ownership and control and the recognition of directorial autonomy. It then considers the relationship between directors and the general meeting, how directors are appointed, categories of directors, principle and policy governing directors’ remuneration, and the fiduciary nature of the office. The issues surrounding corporate governance are also examined, along with the approach of company law in the UK with regards to the structure and functions of the board of directors. Finally, the chapter discusses vacation, removal from office, and disqualification of directors as well as recent statutory reforms (the Small Business, Enterprise and Employment Act 2015) aimed at bolstering the disqualification regime.
16. Corporate governance 2: the UK corporate governance debate
Authors: Dignam Alan , Lowry John
Published: October 2016

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter explores the corporate governance debate in the UK in terms of industry and the government. After presenting the background to the UK debate, it considers UK corporate theory and the industry and government response to the corporate governance debate. It then examines the Sarbanes-Oxley Act that became law in the United States in July 2002; the UK Government’s independent review of non-executive directors (the Higgs Review); the link between corporate governance failure and the recent financial crisis; and the Walker Report (2009) which reviewed problems within the UK financial industry. Finally, it outlines a number of reforms that have been adopted between 2009 and 2012 concerning the financial crisis in general and the Walker Report in particular.
17. Corporate rescue and liquidations in outline
Authors: Dignam Alan , Lowry John
Published: October 2016

Titles in the Core Text series take the reader straight to the heart of the subject, providing focused, concise, and reliable guides for students at all levels. This chapter deals with the regulatory regime governing corporate rescue and liquidations. It first considers two procedures that were introduced by the Insolvency Act 1986 aimed at implementing the objective of corporate rescue: the administration order and the company voluntary arrangement, the former of which has been fundamentally reformed by the Enterprise Act 2002. It then discusses voluntary winding-up by companies, members, and creditors under the 1986 Act, as well as the grounds on which the court may initiate compulsory winding-up. The chapter also examines the consequences of a winding-up petition on dispositions of company property; winding-up in the public interest; the duties and functions of the liquidator; provisions allowing avoidance of transactions entered into prior to liquidation; the personal liability of directors under the Insolvency Act 1986; and distribution of surplus assets following liquidation. Finally, it outlines a number of amendments to the 1986 Act.
4. Transparency
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter focuses on the various requirements for provision of company information for purposes of transparency, particularly with respect to constitution, membership, officers and finances. The required information must be provided to Companies House, where it can be inspected by anyone on payment of the prescribed fees, or at the company’s registered office or an alternative inspection place. Some other information required by the Companies Act 2006, the Insolvency Act 1986, the Insolvency Rules 1986, and related statutory instruments include directors’ service contracts, the company’s registered name and registered number, to be given on business letters, order forms, and websites.
8. Transfer of shares
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter discusses some of the procedures to be followed when transferring some or all of a company member’s shares to another person, and the three important factors on which such procedures depend: whether or not the transfer occurs via sale on the London Stock Exchange; whether the whole or only part of the member’s holding is being transferred; and whether the shares are certificated or uncertificated. After describing share certificates and uncertificated shares, the chapter considers the provisions of Section 544(1) of the Companies Act 2006 regarding share transfer, along with the problem of who should bear the loss when a forged or fraudulent transfer of shares is committed. It also explores transmission of shares on death or bankruptcy and the abolition of bearer share warrants. Finally, it tackles takeovers of public companies and compulsory acquisition of remaining shares.
9. Accounts
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter discusses the requirements calling for directors of a company to prepare accounts once a year, to be presented to the company’s members and filed at Companies House (unless the company is unlimited). The technical rules on the preparation of financial statements are explained. The role of the Financial Reporting Council as the regulator for accountancy, auditing, and financial reporting is also considered. The chapter outlines the accounting requirements, in which every company must keep reasonably accurate accounting records of all financial transactions, from which the directors must prepare annual accounts for each of the company’s financial years. The requirements for group accounts and the procedures for revising accounts that are found to be erroneous are examined as well. The chapter considers a particularly significant case: Caparo Industries plc v Dickman [1990] 2 AC 605.
11. Borrowing and security
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter considers borrowing as an important method of financing a company’s activities and security as a right of recourse against company property if the loan is not repaid on time. It begins by discussing security for financial obligations, paying particular attention to security contracts, the redemption or discharge of security, and the realisation of security. It then turns to the registration of non-possessory security contracts, the priorities of legal and equitable charges, and floating charges as a form of security and their crystallisation. The extent to which the assets of anyone considering extending credit to a company are already charged as security is also explained. The chapter considers three particularly significant court cases: Evans v Rival Granite Quarries Ltd [1910] 2 KB 979; Re Spectrum Plus Ltd [2005] UKHL 41, [2005] 2 AC 680; and Re Yorkshire Woolcombers Association Ltd [1903] 2 Ch 284.
12. Marketable loans
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter is about arrangements by which a company borrows a large sum of money long term from investors, who in turn expect to receive interest payments in addition to the principal. Marketable loans are typically issued in large quantities by financial institutions and specialist investors, and considered wholesale rather than retail investments, and the interests they generate are termed ‘debt securities’, ‘bonds’, or ‘debentures’. This chapter also discusses transfers of debt securities (except when they are convertibles), the nominal value of stocks, the duty of trustees to stockholders, the issuance of stock certificates in connection with marketable loans, and convertibles. Regulations governing contracts for the allotment of debt securities, information for debenture holders, and prospectuses and listing particulars are also examined.
14. Shareholders
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter focuses on the members or shareholders of a company and the way in which they take decisions on the company’s affairs by written resolution using a statutory procedure. It begins by considering the rules which determine who is a member of a company and the information on the members which a company must record. It then describes the mandatory rules of company law that allow members to participate in decision making with regards to a company’s affairs; members’ class rights and the alteration of such rights; and the definitions of holding company, subsidiary, and whollyowned subsidiary. Relevant provisions of the Companies Act 2006 governing written resolutions of private companies, meetings and annual general meetings, voting, adjournment of meetings, and authorisation of political donations by companies are also discussed. The chapter analyses a number of particularly significant cases.
18. Remedies for maladministration
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter considers the remedies available when maladministration occurs, with emphasis on the existence of the company as a separate person. It examines circumstances where a wrong has been done to the company or to individual members, focusing on the proper claimant principle established in Foss v Harbottle (1843) 2 Hare 461, and the possible action that can be taken against company officers who have committed a wrong. It also explains the causes for which a member can file derivative claims; the right of a member to petition the court for relief under the Companies Act 2006 (CA 2006), part 30 (ss 994 to 999); the concept of winding up; the irregularity principle; and when the Secretary of State can intervene in maladministration cases. The chapter cites relevant legislation (Companies Act 1985, Insolvency Act 1986, and CA 2006) and a number of particularly significant court cases.
19. Acting for a company: agency and attribution
Authors: French Derek , Mayson Stephen W. , Ryan Christopher L.
Published: October 2016

This chapter deals with the legal relationship of agency that exists between the company and the agent, explaining the process involved in an agent’s authentication and the execution of documents for the company he or she represents. It then considers two ways in which a company may become contractually bound to another person (a ‘contractor’) under the provisions of the Companies Act 2006: through a written contract to which the company’s common seal is affixed, or when someone has made a contract on behalf of the company. It also discusses the company’s capacity to enter into contracts, with emphasis on the ultra vires rule, and attribution by a court so as to impose criminal liability on a company. A number of court cases relevant to the discussion are cited.
Cosmology with the Square Kilometre Array by SKA-Japan
Authors: Yamauchi Daisuke , Ichiki Kiyotomo , Kohri Kazunori , Namikawa Toshiya , Oyama Yoshihiko , Sekiguchi Toyokazu , Shimabukuro Hayato , Takahashi Keitaro , Takahashi Tomo , Yokoyama Shuichiro , Yoshikawa Kohji
Published: October 2016

In the past several decades, the standard cosmological model has been established and its parameters have been measured to a high precision, while there are still many fundamental questions in cosmology; such as the physics in the very early universe, the origin of the cosmic acceleration, and the nature of dark matter. The forthcoming radio telescope, the Square Kilometre Array (SKA), which will be the world's largest, will be able to open a new frontier in cosmology and will be one of the most powerful tools for cosmology in the coming decade. The cosmological surveys conducted by the SKA would have the potential not only to answer these fundamental questions but also deliver precision cosmology. In this article we briefly review the role of the SKA from the viewpoint of modern cosmology. The cosmological science led by the SKA-Japan Consortium (SKA-JP) Cosmology Science Working Group is also discussed.
Loss of Conventional Melanocytic Markers in Malignant Melanoma and Lymph Node Metastasis; an Uncommon but Dangerous Pitfall
Authors: Chang Oliver , Argenyi Zsolt
Published: October 2016

Although malignant melanomas exhibit a wide range of immunophenotypes, concurrent loss of all 3 conventional melanocytic markers (S-100, Melan-A, and HMB-45) is relatively rare. We report a case of primary malignant melanoma with lymph node metastasis, both exhibiting loss of immunoreactivity for conventional melanocytic markers, while aberrantly expressing epithelial antigenicity (pancytokeratin, CAM 5.2).
Concomitant Cutaneous Langerhans Cell Hystiocytosis and Leukemia Cutis
Authors: Pina-Oviedo Sergio , Torres-Cabala Carlos A. , Miranda Roberto N. , Tetzlaff Michael T. , Singh Selina , Rapini Ronald P. , Prieto Victor G. , Aung Phyu P.
Published: October 2016

Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 109/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis. A skin biopsy showed leukemia cutis in mid and deep dermis. Immunohistochemistry positive for CD4, CD33, CD117, and myeloperoxidase (MPO) supported myeloid and monocytic differentiation. Clusters of Langerhans cells positive for S100, CD1a, CD4, langerin and aberrant CD33 and MPO were found admixed with the AML cells. Langerhans cells were negative for BRAF V600E by immunohistochemistry. The diagnosis of leukemia cutis and concomitant LCH was established. The aberrant expression of CD33 and MPO shared by AML and LCH suggests a possible relationship among these 2 lesions. No LCH or Langerhans cell differentiation was found in the bone marrow. The patient achieved complete remission 4 months after chemotherapy and the skin lesions resolved. To our knowledge, we present for the first time a case of concomitant cutaneous LCH and leukemia cutis.
Vaginal erbium laser as second-generation thermotherapy for the genitourinary syndrome of menopause: a pilot study in breast cancer survivors
Authors: Gambacciani Marco , Levancini Marco
Published: October 2016

Objective:

The aim of this study was to evaluate the efficacy and acceptability of a second generation of vaginal laser treatment, the vaginal erbium laser, as a nonablative photothermal therapy for the management of genitourinary syndrome of menopause in postmenopausal breast cancer survivors.

Methods:

The study was performed using an erbium laser crystal yttrium-aluminum-garnet (XS Fotona Smooth, Fotona, Ljubljana, Slovenia) with a wavelength of 2,940 nm. Forty-three postmenopausal breast cancer survivors were treated with three laser applications every 30 days. Symptoms were assessed before the treatment and after 1, 3, 6, 12, and 18 months, using two methods, subjective Visual Analog Scale (VAS) and objective Vaginal Health Index Score (VHIS). The procedures were performed on an outpatient basis without anesthesia or drug use before or after the intervention.

Results:

From baseline values of 8.5 ± 1.0 cm, vaginal dryness VAS scores were 4.4 ± 1.2 cm after the third treatment and 5.5 ± 1.5 cm 12 months after the treatment (P < 0.01 vs basal values), whereas they were 7.5 ± 1.8 cm after 18 months from the last laser application (NS vs basal values). From baseline values of 7.5 ± 1.5 cm, dyspareunia VAS values decreased to 4.2 ± 0.9 cm after the third treatment and 5.1 ± 1.8 cm 12 months from the last laser application (P < 0.01 vs basal values), whereas they were 6.5 ± 1.8 cm after 18 months from the last laser application (NS vs basal values). VHIS, from baseline values of 8.1 ± 1.3, was 21.0 ± 1.4 after the third treatment and 18 ± 1.8 12 months from the last laser application (P < 0.01 vs basal values), whereas they were 14.8 ± 1.5 cm after 18 months from the last laser application (NS vs basal values). No adverse events were recorded during the study.

Conclusions:

This study suggests that the vaginal erbium laser is effective and safe for the treatment of genitourinary syndrome of menopause in breast cancer survivors.
Effects of aerobic exercise training on ACE and ADRB2 gene expression, plasma angiotensin II level, and flow-mediated dilation: a study on obese postmenopausal women with prehypertension
Authors: Azadpour Noushin , Tartibian Bakhtyar , Koşar Şükran Nazan
Published: October 2016

Objective:

The purpose of this study is to determine the effect of 10 weeks of moderate-intensity aerobic exercise training (MIET) on blood pressure (BP), angiotensin-converting enzyme (ACE) and β2-adrenergic receptor (ADRB2) gene expression in leukocytes, plasma angiotensin II (Ang II), and flow-mediated dilation (FMD) in obese postmenopausal women (PMW) with prehypertension.

Methods:

Twenty-four obese prehypertensive PMW (aged 50-70 y; body mass index ≥30 kg/m2) randomly assigned to control (n = 12) and exercise (n = 12) groups. Exercise group performed MIET (25-40 min/d, 3 d/wk at 50%-70% of heart rate reserve) for 10 weeks. Control group maintained their normal daily physical activity level. Body composition, VO2
max, BP, ACE and ADRB2 gene expression, plasma Ang II, and FMD were measured before and after the training program.

Results:

After MIET, systolic and diastolic BPs decreased by 4.6% and 2.4%, respectively (P < 0.001). Plasma Ang II level decreased by 45.7%, whereas FMD increased by 86% in the exercise group (P < 0.001). Exercise training resulted in a threefold increase in ADRB2 and a fourfold decrease in ACE gene expressions (P < 0.05). Training-induced changes in BP inversely associated with the changes in FMD and ADRB2 (r values range −0.55 to −0.78), and positively associated with Ang II and ACE (r values range 0.68-0.86) (P < 0.001).

Conclusions:

Ten weeks of MIET modulates ACE and ADRB2 gene expression, decreases Ang II plasma levels, and improves endothelial function in obese PMW, and these alterations are associated with reduction in BP.
Time-to-First Discontinuation, Adherence and Persistence in New Users of Second-Generation Antipsychotics
Authors: Ndukwe Henry C. , Nishtala Prasad S.
Published: October 2016

Consensus guidelines which are applicable in New Zealand and worldwide recommend that the duration of exposure to antipsychotics not exceed 12 weeks, unless justified for mental illnesses like schizophrenia and severe psychotic symptoms which require longer treatment. There has been limited information on time-to-first discontinuation (TTFD) for second-generation antipsychotics (SGAs) in a real world population setting in older people. The study objective was to compare TTFD, adherence, and persistence for individual SGA new users among people 65 years and older. A cohort of 30,297 SGA new users was followed up for antipsychotic discontinuation from January 1, 2006, to December 31, 2012. Data for oral formulations were extracted using health care databases from the New Zealand Ministry of Health. The TTFD, adherence, and persistence were defined using (dispensing gap ≥ 91 days, variable medication possession ratio ≥ 0.8, and gap duration < 91 days between refills), respectively. Kaplan-Meier curves and Cox regression analysis were used to estimate and adjust for outcomes. The overall TTFD in SGA new users was 192.3 days (95% confidence interval [CI], 177.6–206.9), mean age at dispensing was 80.9 years (SD, 8.1 years), and 60.3% were women. The TTFD for was shortest for risperidone, 101.3 days (95% CI, 85.0–117.7; P = 0.03) compared with clozapine, 68.3 days (95% CI: 43.7, 92.9). The adjusted all-cause TTFD risk for risperidone, olanzapine, quetiapine, or ziprasidone (hazard ratios, 0.54, 0.29, 0.22, and 0.08, respectively) was significantly lower than clozapine. The TTFD risk in the nonadherent compared with the adherent group was more than 3 times.
Teflon Injection into the Trachea Causes Predictable Fibroblastic Response and Collagen Deposition
Authors: Longoria Javier A. , Fujiwara Miwa , Guerra Catalina , Lee Jeffrey L. , Sassoon Catherine S.H. , Mazdisnian Farhad
Published: October 2016

Background:

Expiratory central airway collapse is an increasingly recognized abnormality of the central airways and may be present in as many as 22% of patients evaluated for chronic obstructive pulmonary disease and/or asthma. Many current treatment options require invasive procedures that have been shown to cause significant morbidity and mortality. To test the hypothesis that Teflon injection will induce sufficient fibroblast proliferation and collagen deposition, we evaluated the time course on the effect of Teflon injection in the posterior membranous trachea on the histopathology of the tracheobronchial tree.

Methods:

Six Yucatan Pigs were assigned to undergo general anesthesia and injection of 0.3 to 0.5 mL of sterile Teflon paste in 50% glycerin into the posterior membranous tracheal wall. A control pig received an equivalent volume of glycerin. Animals were euthanized in predefined intervals and tracheas were excised and examined under light microscopy for identifying fibroblast proliferation and collagen deposition.

Results:

Compared with the control pig, the Teflon injection site showed tissue reaction of fibrohistiocytic proliferation and subsequent collagen deposition in all animals. Furthermore, the increased fibroblast proliferation and collagen deposition were time dependent (P<0.01).

Conclusion:

This pilot study demonstrates histopathologic changes in the trachea after Teflon injection, comprised of increased fibroblast activity and collagen deposition that could be of potential use in creating greater airway rigidity in patients with sever diffuse excessive dynamic airway collapse.
Posterior Fossa Spontaneous Cerebrospinal Fluid Leaks
Authors: Wick Cameron C. , Killeen Daniel E. , Clark Michael , Kutz Joe Walter , Isaacson Brandon
Published: October 2016

Objective:

Describe the diagnosis and management of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks that originate from the posterior fossa.

Study Design:

Retrospective case review.

Setting:

Tertiary university hospital.

Patients:

Adult patients from 2005 to 2015 who underwent surgical repair of a spontaneous lateral skull base CSF leak with intraoperative confirmation of a posterior fossa leak source.

Intervention:

Surgical repair.

Main Outcome Measures:

CSF leak resolution.

Results:

Five patients had CSF leaks from the posterior fossa. The mean age at presentation was 54 years old (range, 19–79), the mean body mass index (BMI) was 32.6 (standard deviation [SD], 8.4), and the mean follow-up length was 34.6 months (SD, 19.4). Presentations did not differ from CSF leaks through middle fossa defects, including three patients with a history of meningitis and all patients with clear otorrhea following tympanostomy tube placement. All patients had resolution of the leak after surgical repair, but two patients required revision surgery for persistent leaks and one patient had a postoperative infection. Surgical approaches included one middle fossa, two transmastoid, one combined middle fossa/transmastoid, and one transcanal. Radiographic studies suggested a posterior fossa source in all cases but findings were often subtle.

Conclusion:

Posterior fossa CSF leaks represent a rare subset of spontaneous lateral skull base leaks. Diligent radiographic review and intraoperative assessment of the posterior fossa plate are crucial. The size and location of the defect dictates the optimal surgical approach. Surgeons should consider a posterior fossa source in failed repairs or when the initial surgery did not fully evaluate the posterior fossa plate.
Why are patients still getting and dying from acute kidney injury?
Authors: Kellum John A.
Published: October 2016

Purpose of review

Acute kidney injury is common and is associated with increased morbidity and mortality. Rates of acute kidney injury in most settings remain high and in some settings are increasing. Moreover, outcomes associated with acute kidney injury remain relatively poor. This review focuses on recent advances in understanding of acute kidney injury and discusses possible interventions based on these advances.

Recent findings

Acute kidney injury is not a disease with a single etiology and clinical course but rather a loose collection of syndromes whose unifying phenotype is an acute loss of glomerular filtration. Traditional taxonomy based on anatomic locations (pre, intra, and post) in reference to the kidney is overly simplistic and has given way to specific ‘endotypes’ including hepatorenal, cardiorenal, nephrotoxic, and sepsis-associated and these syndromes all have unique pathophysiologies and treatments. Our tendency to lump all of these clinical syndromes into a single disease and seek a single treatment has led to the profound lack of progress observed in terms of improving outcomes. The hope is that this is about to change.

Understanding the epidemiology, pathogenesis, and pathophysiology of acute kidney injury is critical to achieving improved outcomes for the millions of patients who develop this loose constellation of syndromes.
Does Sotalol Still Have a Role in the Management of Arrhythmias?
Authors: Semasinghe Bandaralage Sahan P. , Nirthanan Selvanayagam , Niranjan Selvanayagam
Published: October 2016

Despite proven effectiveness in treating tachyarrhythmias, sotalol is proarrhythmic and can cause torsades de pointes. Given the emergence of studies that show no benefit from rhythm control strategies in managing atrial fibrillation, as well as the introduction of nonpharmacological approaches to treating arrhythmias, we felt it necessary to ascertain if there was any role for sotalol given its side effects. Review of the literature regarding sotalol use in the prevention and treatment of supraventricular and ventricular tachyarrhythmias seems to show that more effective and safer agents and nonpharmacological alternatives are currently available. However, sotalol still seems to be useful in preventing supraventricular tachyarrhythmias postcardiac surgery and in reverting hemodynamically stable sustained ventricular tachycardias in the setting of coronary artery disease. Its role in the prevention of tachyarrhythmias in the setting of arrhythmogenic right ventricular cardiomyopathy requires further investigation.
Who cares about the history of science?
Authors: Chang Hasok
Published: October 2016

The history of science has many functions. Historians should consider how their work contributes to various functions, going beyond a simple desire to understand the past correctly. There are both internal and external functions of the history of science in relation to science itself; I focus here on the internal, as they tend to be neglected these days. The internal functions can be divided into orthodox and complementary. The orthodox function is to assist with the understanding of the content and methods of science as it is now practised. The complementary function is to generate and improve scientific knowledge where current science itself fails to do so. Complementary functions of the history of science include the raising of critical awareness, and the recovery and extension of past scientific knowledge that has become forgotten or neglected. These complementary functions are illustrated with some concrete examples.
How well can we quantify dust deposition to the ocean?
Authors: Anderson R. F. , Cheng H. , Edwards R. L. , Fleisher M. Q. , Hayes C. T. , Huang K.-F. , Kadko D. , Lam P. J. , Landing W. M. , Lao Y. , Lu Y. , Measures C. I. , Moran S. B. , Morton P. L. , Ohnemus D. C. , Robinson L. F. , Shelley R. U.
Published: October 2016

Deposition of continental mineral aerosols (dust) in the Eastern Tropical North Atlantic Ocean, between the coast of Africa and the Mid-Atlantic Ridge, was estimated using several strategies based on the measurement of aerosols, trace metals dissolved in seawater, particulate material filtered from the water column, particles collected by sediment traps and sediments. Most of the data used in this synthesis involve samples collected during US GEOTRACES expeditions in 2010 and 2011, although some results from the literature are also used. Dust deposition generated by a global model serves as a reference against which the results from each observational strategy are compared. Observation-based dust fluxes disagree with one another by as much as two orders of magnitude, although most of the methods produce results that are consistent with the reference model to within a factor of 5. The large range of estimates indicates that further work is needed to reduce uncertainties associated with each method before it can be applied routinely to map dust deposition to the ocean. Calculated dust deposition using observational strategies thought to have the smallest uncertainties is lower than the reference model by a factor of 2–5, suggesting that the model may overestimate dust deposition in our study area.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Nitrite isotopes as tracers of marine N cycle processes
Authors: Casciotti Karen L.
Published: October 2016

Nitrite (NO
2
−
) is a key intermediate in the marine nitrogen (N) cycle. It is produced and consumed throughout the ocean by the dominant processes driving the distribution, availability and speciation of N. However, the accumulation of nitrite is typically confined to depths near the base of the sunlit euphotic zone and in oxygen-deficient zones. These features are known as the primary and secondary nitrite maximum (PNM and SNM), respectively. The processes controlling nitrite accumulation in these features are not fully understood, but are thought to depend on the microbial community composition and its response to environmental conditions. A variety of approaches have been applied to understanding these features since their discovery, with the stable N and oxygen (O) isotope measurements of nitrite being added to this toolkit most recently. Large variations in nitrite N isotope ratios (
15
N/
14
N) and dramatic depletions in
15
N contrast with more consistent nitrite O isotope ratios (
18
O/
16
O) in the SNM. These signals provide unique information about the mechanisms of nitrite consumption in the SNM. By contrast, nitrite in the PNM shows less variation in
15
N/
14
N, but variations in
18
O/
16
O that provide insight into the mechanisms and rates of N cycling there. This review presents a synthesis of nitrite isotope measurements in the marine environment, highlighting the insights that have been gained from these measurements.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Coastal ocean and shelf-sea biogeochemical cycling of trace elements and isotopes: lessons learned from GEOTRACES
Authors: Charette Matthew A. , Lam Phoebe J. , Lohan Maeve C. , Kwon Eun Young , Hatje Vanessa , Jeandel Catherine , Shiller Alan M. , Cutter Gregory A. , Thomas Alex , Boyd Philip W. , Homoky William B. , Milne Angela , Thomas Helmuth , Andersson Per S. , Porcelli Don , Tanaka Takahiro , Geibert Walter , Dehairs Frank , Garcia-Orellana Jordi
Published: October 2016

Continental shelves and shelf seas play a central role in the global carbon cycle. However, their importance with respect to trace element and isotope (TEI) inputs to ocean basins is less well understood. Here, we present major findings on shelf TEI biogeochemistry from the GEOTRACES programme as well as a proof of concept for a new method to estimate shelf TEI fluxes. The case studies focus on advances in our understanding of TEI cycling in the Arctic, transformations within a major river estuary (Amazon), shelf sediment micronutrient fluxes and basin-scale estimates of submarine groundwater discharge. The proposed shelf flux tracer is 228-radium (
T
1/2
 = 5.75 yr), which is continuously supplied to the shelf from coastal aquifers, sediment porewater exchange and rivers. Model-derived shelf
228
Ra fluxes are combined with TEI/
228
Ra ratios to quantify ocean TEI fluxes from the western North Atlantic margin. The results from this new approach agree well with previous estimates for shelf Co, Fe, Mn and Zn inputs and exceed published estimates of atmospheric deposition by factors of approximately 3–23. Lastly, recommendations are made for additional GEOTRACES process studies and coastal margin-focused section cruises that will help refine the model and provide better insight on the mechanisms driving shelf-derived TEI fluxes to the ocean.

This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Phylogenetic Characterization of the Energy-taxis Receptor Aer inPseudomonasand Phenotypic Characterization inP. pseudoalcaligenesKF707
Authors: Booth Sean C. , Turner Raymond J.
Published: October 2016

Chemotaxis allows bacteria to sense gradients in their environment and respond by directing their swimming. Aer is a receptor that, instead of responding to a specific chemoattractant, allows bacteria to sense cellular energy levels and move towards favourable environments. InPseudomonas, the number of apparent Aer homologs differs between the only two species it had been characterized in,P. aeruginosaandP. putida. Here we combined bioinformatic approaches with deletional mutagenesis inP. pseudoalcaligenesKF707 to further characterize Aer. It was determined that the number of Aer homologs varies between 0-4 throughout thePseudomonasgenus, and they were phylogenetically classified into 5 subgroups. We also used sequence analysis to show that these homologous receptors differ in their HAMP signal transduction domains. Genetic analysis also indicated that some Aer homologs have likely been subject to horizontal transfer.P. pseudoalcaligenesKF707 was unique among species for having three Aer homologs as well as the receptors CttP and McpB. Phenotypic characterization in this species showed the most prevalent homolog of Aer was key, but not essential for energy-taxis. This study demonstrates that energy-taxis inPseudomonasvaries between species and provides a new naming convention and associated phylogenetic details for Aer chemoreceptors.
Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular development and homeostasis
Authors: Sleigh James N. , Gómez-Martín Adriana , Schiavo Giampietro
Published: October 2016

It remains a mystery how dominantly inherited mutations in the housekeeping geneGARS, which encodes glycyl-tRNA synthetase (GlyRS), mediate selective peripheral nerve toxicity resulting in the currently incurable Charcot-Marie-Tooth disease type 2D (CMT2D). A recent study identified the transmembrane receptor protein neuropilin 1 (Nrp1) as a substrate for aberrant extracellular binding of mutant GlyRS. Formation of the Nrp1/mutant GlyRS complex antagonises the interaction of Nrp1 with one of its main natural ligands, vascular endothelial growth factor-A (VEGF-A), contributing to neurodegeneration. Reduced binding of Nrp1 to VEGF-A is known to disrupt blood vessel development and growth. We therefore analysed capillary architecture at early and later symptomatic time points in CMT2D mouse muscles, retina, and sciatic nerve, as well as in embryonic hindbrain. Assessing capillary diameter, density, and branching, we observed no differences between wild-type and mutant animals from embryonic development to three months, spanning the duration over which numerous sensory and neuromuscular phenotypes manifest. This work indicates that mutant GlyRS-mediated disruption of Nrp1/VEGF-A signalling is permissive to capillary maturation and maintenance in CMT2D mice.

Summary Statement

Although the multi-functional neuropilin 1/VEGF-A signalling pathway is impaired by dominant pathogenic GlyRS variants, the vascular system remains unperturbed inGarsmutant mice.
Centrifuge: rapid and sensitive classification of metagenomic sequences
Authors: Kim Daehwan , Song Li , Breitwieser Florian P. , Salzberg Steven L.
Published: October 2016

Centrifuge is a novel microbial classification engine that enables rapid, accurate, and sensitive labeling of reads and quantification of species on desktop computers. The system uses an indexing scheme based on the Burrows-Wheeler transform (BWT) and the Ferragina-Manzini (FM) index, optimized specifically for the metagenomic classification problem. Centrifuge requires a relatively small index (4.2 GB for 4078 bacterial and 200 archaeal genomes) and classifies sequences at very high speed, allowing it to process the millions of reads from a typical high-throughput DNA sequencing run within a few minutes. Together, these advances enable timely and accurate analysis of large metagenomics data sets on conventional desktop computers. Because of its space-optimized indexing schemes, Centrifuge also makes it possible to index the entire NCBI nonredundant nucleotide sequence database (a total of 109 billion bases) with an index size of 69 GB, in contrast to k-mer-based indexing schemes, which require far more extensive space.
Demand-Driven Control of Root ATP Sulfurylase Activity and SO42- Uptake in Intact Canola (The Role of Phloem-Translocated Glutathione)
Authors: Lappartient A. G. , Touraine B.
Published: October 2016

The activity of ATP sulfurylase extracted from roots of intact canola (Brassica napus L. cv Drakkar) increased after withdrawal of the S source from the nutrient solution and declined after refeeding SO42- to S-starved plants. The rate of SO42- uptake by the roots was similarly influenced. Identical responses were obtained in SO42- -fed roots when one-half of the root system was starved for S. The internal levels of SO42- and glutathione (GSH) declined after S starvation of the whole root system, but only GSH concentration declined in +S roots of plants from split root experiments. The concentration of GSH in phloem exudates decreased upon transfer of plants to S-free solution. Supplying GSH or cysteine to roots, either exogenously or internally via phloem sap, inhibited both ATP sulfurylase activity and SO42- uptake. Buthionine sulfoximine, an inhibitor of GSH synthesis, reversed the inhibitory effect of cysteine on ATP sulfurylase. It is hypothesized that GSH is responsible for mediating the responses to S availability. ATP sulfurylase activity and the SO42- uptake rate are regulated by similar demand-driven processes that involve the translocation of a phloem-transported message (possibly GSH) to the roots that provides information concerning the nutritional status of the leaves.