bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Tobacco Cessation via Health Coaching: An Institutional Case Report
Authors: Sforzo Gary A. , Kaye Miranda , Ayers Gale D. , Talbert Betina , Hill Marilyn
Published: September 2014

Background:

Tobacco abuse is a well-recognized scourge on health and healthcare costs. Attempts to facilitate tobacco cessation are rarely better than marginally effective.

Primary Objective:

To describe an observational trial of an existing and highly successful tobacco cessation program featuring health coaching as the primary intervention. Core components of program design and data are presented and may serve as a model for other public health settings.

Methods:

Health coaching and three complementary program components (auriculotherapy, alpha-electrical stimulation, and relaxation techniques) are presented. Quit rates at 6 months for 161 patients over 3 years are provided featuring 30-day point prevalence smoke free and intent-to-treat values. Comparisons for telephonic vs in-clinic health coaching, free choice vs mandated participation, and program costs are provided.

Results:

Point prevalence quit rate was 88.7% while the more conservative intent-to-treat quit rate was 51.6%. Telephonic and in-clinic health coaching were not significantly different at any time point. Smoke-free rates at 6 and 12 months were 76.9% and 63.2%, respectively.

Conclusions:

Two cost-effective smoking cessation models featuring health coaching are presented. Point prevalence (30–day) above 80% and an enduring effect was seen. Personal and societal burdens (health and financial) of tobacco use might be greatly impacted if such programs were successfully implemented on a larger scale.
Two Different Strategies to Facilitate Involvement in Healthcare Improvements: A Swedish County Council Initiative
Authors: Andersson Ann-Christine , Idvall Ewa , Perseius Kent-Inge , Elg Mattias
Published: September 2014

Background:

From a management point of view, there are many different approaches from which to choose to engage staff members in initiatives to improve performance.

Objective:

The present study evaluated how two different types of improvement strategies facilitate and encourage involvement of different professional groups in healthcare organizations.

Methods/Design:

Empirical data of two different types of strategies were collected within an improvement project in a County Council in Sweden. The data analysis was carried out through classifying the participants’ profession, position, gender, and the organizational administration of which they were a part, in relation to their participation.

Setting:

An improvement project in a County Council in Sweden.

Participants:

Designed Improvement Processes consisted of n=105 teams and Intrapreneurship Projects of n=202 projects.

Intervention:

Two different types of improvement strategies Designed Improvement Processes and Intrapreneurship Projects.

Main Outcome Measures:

How two different types of improvement strategies facilitate and encourage involvement of different professional groups in healthcare organizations.

Results:

Nurses were the largest group participating in both improvement initiatives. Physicians were also well represented, although they seemed to prefer the less structured Intrapreneurship Projects approach. Assistant nurses, being the second largest staff group, were poorly represented in both initiatives. This indicates that the benefits and support for one group may push another group aside.

Conclusions:

Managers need to give prerequisites and incentives for staff who do not participate in improvements to do so. Comparisons of different types of improvement initiatives are an underused research strategy that yields interesting and thoughtful results.
Integrative Therapies for Low Back Pain that Include Complementary and Alternative Medicine Care: A Systematic Review
Authors: Kizhakkeveettil Anupama , Rose Kevin , Kadar Gena E.
Published: September 2014

Study Design:

Systematic review of the literature.

Objective:

To evaluate whether an integrated approach that includes different Complementary and Alternative Medicine (CAM) therapies combined or CAM therapies combined with conventional medical care is more effective for the management of low back pain (LBP) than single modalities alone.

Summary of Background Data:

LBP is one of the leading causes of disability worldwide, yet its optimal management is still unresolved.

Methods:

The PRISMA Statement guidelines were followed. The Cochrane Back Review Group scale was used to rate the quality of the studies found.

Results:

Twenty-one studies were found that met the inclusion criteria. The CAM modalities used in the studies included spinal manipulative therapy, acupuncture, exercise therapy, physiotherapy, massage therapy, and a topical ointment. Twenty studies included acupuncture and/or spinal manipulative therapy. Nine high quality studies showed that integrative care was clinically effective for the management of LBP. Spinal manipulative therapy combined with exercise therapy and acupuncture combined with conventional medical care or with exercise therapy appears to be promising approaches to the management of chronic cases of LBP.

Conclusions:

There is support in the literature for integrated CAM and conventional medical therapy for the management of chronic LBP. Further research into the integrated management of LBP is clearly needed to provide better guidance for patients and clinicians.
Experimental modeling of infrasound emission from slug bursting on volcanoes
Authors: Sánchez C. , Álvarez B. , Melo F. , Vidal V.
Published: September 2014

The acoustic signal produced by gas slugs bursting at volcano vents is investigated by means of laboratory experiments. In order to explore the transition between linear and nonlinear acoustics, we model the bubble by an overpressurized cylindrical cavity closed by a membrane. We find that the acoustic waveform inside and outside the cavity, produced by the membrane bursting, is well described by the linear acoustics equations and a monopole source model up to an initial overpressure inside the cavity of about 24 kPa. For higher overpressure, the amplitude inside the conduit is smaller than the linear prediction, whereas the amplitude measured outside is larger. The frequency content remains harmonic, even at high initial overpressure. Changing the bursting depth in the conduit does not change the scaling of the amplitudes but affects the waveform and energy partitioning. We show that the energy of the first signal period is about 30% of the total acoustic energy and can be used as a good estimate, with a geometrical correction to account for the bursting depth.
Detection of detached dust layers in the Martian atmosphere from their thermal signature using assimilation
Authors: Navarro T. , Forget F. , Millour E. , Greybush S. J.
Published: September 2014

Airborne dust modifies the thermal structure of the Martian atmosphere. The Mars Climate Sounder (MCS) first revealed local maxima of dust mass mixing ratio detached from the surface, not reproduced by global climate models (GCM). In this paper, the thermal signature of such detached layers is detected using data assimilation, an optimal combination of a GCM and observations. As dust influences the atmospheric temperatures, MCS temperature profiles are used to estimate the amount of dust in the atmosphere. Data assimilation of only MCS temperature information reproduces detached dust layers, independently confirming MCS's direct observations of dust. The resulting analyzed state has a smaller bias than an assimilation that does not estimate dust. This makes it a promising technique for Martian data assimilation, which is intended to support weather forecasting and weather research on Mars.
Using the kappa function to investigate hot plasma in the magnetospheres of the giant planets
Authors: Carbary J. F. , Kane M. , Mauk B. H. , Krimigis S. M.
Published: September 2014

Planetary magnetospheres contain two general classes of charged particles: low energy “thermal” particles (generally E < 1 keV) usually described by a Maxwellian distribution and “hot” particles (E > 10 keV), variously called superthermal or “energetic” particles, which are described by a power law distribution. The kappa or κ function combines aspects of both Maxwellian and power law forms to provide a reasonably complete description of the particle distribution from low to high energies. Fits of the data to the kappa distribution can reveal particle density, temperature, pressure, and convection velocity, all of which are key parameters of magnetospheric physics. This paper summarizes the use of the kappa distribution and its variants to investigate the plasma properties of the magnetospheres of the giant planets Jupiter, Saturn, Uranus, and Neptune. While the κ function was used to derive convective motions in previous investigations, temperatures, and pressures at Jupiter and Saturn, it was not an optimum fit for hot plasmas at Uranus and Neptune, and in many instances may not be the optimum representation of magnetospheric plasmas.
Swell dissipation by induced atmospheric shear stress
Authors: Perignon Y. , Ardhuin F. , Cathelain M. , Robert M.
Published: September 2014

Observations of swell dissipation across oceans reveal a significant loss of energy that can be the result of many of processes. Among these candidate mechanisms, this paper examines the properties of the viscous air‐sea boundary layer driven by swells in order to characterize the induced atmospheric flow regime and its associated viscous dissipation over swells. A series of 3‐D numerical experiments is carried out with a RANS model and appropriate turbulence closure. These experiments reveal a laminar to turbulent transition in the near free‐surface region for a common range of characteristic amplitudes and periods of swells under stationary conditions. At low Reynolds number, laminar conditions prevail and computed decay rates conform to the analytical formulation μν of the Stokes interfacial boundary layer for this problem. The turbulent regimes are characterized as well, and the new decay rates follow a nondimensional relation
above
(e.g., amplitude larger than 1.1 m for a 14 s monochromatic wave period). Typical decay rates are up to 4 times above the laminar values, which is a factor 10 less than the largest rates estimated for oceanic conditions. A sensitivity analysis is finally conducted to evaluate the influence of the stationary hypothesis. It demonstrates a short setup length and low relative variations of the unsteady decay rates for laminar, transitioning and developed turbulent conditions, which confirms the evaluation of steady decay rates.
Water vapor turbulence profiles in stationary continental convective mixed layers
Authors: Turner D. D. , Wulfmeyer V. , Berg L. K. , Schween J. H.
Published: September 2014

The U.S. Department of Energy Atmospheric Radiation Measurement (ARM) program's Raman lidar at the ARM Southern Great Plains site in north central Oklahoma has collected water vapor mixing ratio (q) profile data more than 90% of the time since October 2004. Three hundred (300) cases were identified where the convective boundary layer was quasi‐stationary and well mixed for a 2 h period, and q mean, variance, third‐order moment, and skewness profiles were derived from the 10 s, 75 m resolution data. These cases span the entire calendar year, and demonstrate that the q variance profiles at the mixed layer (ML) top changes seasonally and is strongly related to the gradient of q across the interfacial layer. The q variance at the top of the ML shows only weak correlations (r < 0.3) with sensible heat flux, Deardorff convective velocity scale, and turbulence kinetic energy measured at the surface. The median q skewness profile is most negative at 0.85 zi, zero at approximately zi, and positive above zi, where zi is the depth of the convective ML. The spread in the q skewness profiles is smallest between 0.95 zi and zi. The q skewness at altitudes between 0.6 zi and 1.2 zi is correlated with the magnitude of the q variance at zi, with increasingly negative values of skewness observed lower down in the ML as the variance at zi increases, suggesting that in cases with larger variance at zi there is deeper penetration of the warm, dry free tropospheric air into the ML.
Transfer
RNA
Synthesis and Regulation
Authors: Hori Hiroyuki , Tomikawa Chie , Hirata Akira , Toh Yukimatsu , Tomita Kozo , Ueda Takuya , Watanabe Kimitsuna
Published: September 2014

Transfer ribonucleic acid (tRNA)
, which is primarily transcribed from tRNA genes by RNA polymerase, matures via several steps: processing, splicing, CCA addition and post‐transcriptional modifications. Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases. In addition, some primary transcripts contain introns, which are spliced out by specific endonucleases or in self‐splicing reactions. The ligation of exons generally requires a tRNA ligase. In some species, the CCA sequences present at the 3′‐termini of all mature tRNAs are not encoded in the tRNA genes, but are added post‐transcriptionally by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides, generated by specific tRNA modification enzymes or guide RNA systems. These modified nucleotides are involved in stabilisation of tRNA structure, decoding, tRNA quality control, regulation of subcellular localisation of tRNAs and immune responses against infectious organisms.

Key Concepts:

tRNA is transcribed from tRNA genes by RNA polymerase, and matures through processing, splicing, CCA addition and post‐transcriptional modification.

Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes, and Maf1 in eukaryotes), depending on the nutrient conditions of the cell.

The relative amounts of tRNA are regulated by several factors: copy number of tRNA genes, transcriptional activity, and degradation by various nucleases.

Primary transcripts of tRNA genes contain extra 5′ and 3′ sequences, which are removed by a set of nucleases.

In some cases, tRNA transcripts contain introns, which are spliced out by specific endonuclease or the group I intron reaction. The two resultant fragments are joined by RNA ligase or the self‐splicing reaction.

CCA‐adding enzyme regulates the amount of active tRNA by introducing the CCA sequence at the
C
‐terminus of tRNA.

tRNA possesses a variety of modified nucleotides, which are introduced by specific tRNA modification enzymes.

Several modifications of tRNA play important roles in the translation process: promotion, expansion, restriction, and/or alteration of codon–anticodon interactions; stabilisation of tRNA structure; recognition by translation factors and aminoacyl‐tRNA synthetases; etc.

Several modified nucleotides in tRNA are involved in RNA quality control systems, regulation of tRNA transport, infection and immune responses.
Transfer
RNA
Recognition and Aminoacylation by Synthetases
Authors: Giegé Richard , Eriani Gilbert
Published: September 2014

Fidelity of
transfer ribonucleic acid (tRNA)
charging by amino acids ensures correct translation of the genetic code into proteins. Charging is catalysed by a set of enzymes known as aminoacyl‐tRNA synthetases. Owing to the degeneracy of the genetic code, some of the different tRNAs have the same amino acid attached to them. Specificity of charging obeys universal rules and is ensured by positive elements, the identity determinants unique to each tRNA and responsible for its recognition by the cognate synthetase, and negative elements, the antideterminants that prevent false recognitions. To fulfil the aminoacylation specificity and prevent noncognate aminoacyl‐tRNA delivery to the ribosome, some synthetases also mediate proofreading reactions that increase fidelity of the tRNA charging. In such reactions, misactivated amino acids or mischarged tRNAs are checked in specific sites and noncognate products are hydrolysed. However, mischarging is beneficial under certain stress circumstances or when catalysed by nondiscriminatory synthetases, and represents a driving force in evolution.

Key Concepts:

Translational expression of the genetic code refers to aminoacyl‐tRNA‐ and ribosome‐dependent decoding of genes into proteins, a process highly dependent on fidelity of tRNA aminoacylation by synthetases.

The rules that account for the aminoacylation identity of tRNAs are referred to as the second genetic code.

The RNA operational code is encoded in the acceptor stem of tRNA and is crucial for recognition by aminoacyl‐tRNA synthetases and specific aminoacylation.

Allostery in tRNA‐synthetase systems concerns long‐range transfer of chemical information (up to 75 Å) to the synthetase catalytic site (through the body of tRNA and/or synthetase) triggered by contacts of tRNA identity determinants with the synthetase.

Engineering the identity of tRNA‐synthetase systems allows reprogramming the genetic code.
DNADamage
Authors: Limpose Kristin , Corbett Anita H , Doetsch Paul W
Published: September 2014

Deoxyribonucleic acid (DNA)is composed of bases that code for all functions of life. Biochemical and physical events that alter DNA include base damage and single‐ and double‐strand break (DSB) induction. Cellular DNA damage is induced through exposure to environmental chemicals and radiation, as well as from endogenous sources including normal cellular metabolism. Notably, DNA damage can occur in both the nuclear and mitochondrial genomes. Damaged DNA can lead to deleterious biological outcomes including cancer development and other diseases. Whether biological consequences arise from DNA damage largely depends on the DNA repair capacity of the cell and the interactions of the DNA damage and DNA replication machinery. Detection and measurement of cellular DNA damage is accomplished through methods that vary in sensitivity and DNA damage context.

Key Concepts:

Estimated rates of induction of various deoxyribonucleic acid (DNA) lesions, including spontaneous hydrolysis and oxidative DNA damage, have been determined.

Potential biological outcomes of DNA damage include physiological conditions such as cancer, neurodegenerative diseases, heart disease and ageing.

Various exogenous and endogenous sources induce DNA base lesions and strand breaks that can be detected by various molecular and biochemical methods.

Incorporation of damaged deoxyribonucleotides during DNA synthesis can occur owing to errors committed by DNA polymerases and/or disruptions of nucleotide pool balance.

Many of the features resulting from DNA packing into chromatin, including DNA–protein interactions and sequence context, greatly affect the manner in which damage is distributed within the genome.

Cancer mutational signatures arise from context‐dependent DNA damage, and certain signatures can be attributed to specific types of DNA damage.

DNA is often the target of chemotherapeutic drugs used to treat cancer, resulting in tumour cell death.

Mitochondrial DNA damage can increase reactive oxygen species, leading to cell death, and in certain instances give rise to mutations that contribute to cancer phenotypes.
Plant Gums
Authors: BeMiller James N
Published: September 2014

The term gum is commonly applied to water‐soluble, non‐starch polysaccharides of commerce. The plants from which plant gums are obtained are both higher land plants and red and brown marine algae/seaweeds. Those from higher land plants may be cell‐wall constituents, energy‐storing/carbon‐storing substances that can be extracted from plant tissues, or exudates from wounds in the bark. Plant and other gums are used in practical applications primarily to thicken or gel aqueous systems and to control water. They may also function as adhesives, crystallisation inhibitors, emulsifying agents, emulsion stabilisers, encapsulating agents, film formers, foam stabilisers, suspending agents, suspension stabilisers or syneresis inhibitors and impart other specific properties.

Key Concepts:

Water‐soluble, non‐starch polysaccharides from plants and other sources are generally referred to as gums when used commercially.

Certain hydrophobic substances, such as chicle and resinous saps, are also called gums.

Plant gums do not have common functional roles in the plants from which they are obtained.

Each of the multitude of plant gums is unique in terms of chemical structure and physical properties.

Some plant gums find applications in aqueous systems for a variety of purposes, among which are as thickening, gel‐forming and water‐holding agents and emulsion and suspension stabilisers.
Neutron Diffraction
Authors: Bradshaw Jeremy P
Published: September 2014

Neutron diffraction, a technique analogous to X‐ray diffraction, is well‐suited to the study of biological materials. By differentiating between hydrogen and its heavier isotope, deuterium, neutron diffraction is able to provide detailed information about the hydrogen atoms within biological macromolecules. It allows biologists to study solvation effects, protonation–deprotonation equilibria, hydrogen bonding and other types of chemistry, all of which are invisible to X‐ray techniques. Recent years have seen the construction of new neutron research facilities, notably the Spallation Neutron Source in the USA, the World's brightest neutron source. Even with such high‐flux sources, the intensity of neutrons hitting the sample is several orders of magnitude lower than a typical X‐ray experiment. However, the nonionizing nature of neutrons means that beam damage to the specimen is low, even over extended exposure times.

Key Concepts:

Neutron diffraction is closely related to the complementary technique of X‐ray crystallography, a method that led to a revolution in biological sciences.

Hydrogen plays a central role in many biological processes, but is invisible to X‐rays.

Neutrons are able to distinguish between hydrogen and deuterium, so selective deuteration of a single molecule or group can be used to locate it within a complex macromolecular assembly.

The neutron scattering contrast of samples can be controlled by changing the deuterium content of the solvent (water–heavy water exchange).

Neutrons have the ability to discriminate between nitrogen, carbon and oxygen, which can be difficult with X‐rays.

Neutron experiments are carried out at large scale, national or international neutron research centres, because production of the neutrons requires a nuclear reactor or a spallation source.

Animal behaviourists must participate in conservation planning to protect the future of biodiversity.

Lipid bilayers provide the fundamental architecture of biological membranes.
Polymerase Chain Reaction (PCR): Specialised Applications
Authors: Frohman Michael A
Published: September 2014

The polymerase chain reaction (PCR) is a technique that rapidly amplifies selected subsets ofdeoxyribonucleic acid (DNA)orcomplementary DNA (cDNA)from initially complex biological mixtures. The efficiency of amplification or sequence of the amplified material can then be examined for many purposes, including genotyping or the characterisation of new genes, gene expression patterns, mutations or polymorphisms. Quantitative‐PCR (QT‐PCR) has become practical and popular over the past decade with the generation of libraries of individual primer sets and arrayed sets of primers by commercial entities. QT‐PCR machines can assay up to 384 samples at once, permitting the complete analysis of expression of families of genes, such as signalling kinases or cytokines, in a single experiment. Rapid amplification of cDNA ends‐PCR has also become popular to identify microRNAs (ribonucleic acid). PCR is highly useful in structural biology to rapidly modify the boundaries of protein domains intended for crystallisation and in genomics for high‐throughput sequencing.

Key Concepts:

PCR can be conducted on vanishingly small amounts of material.

PCR can be used for rapid genotyping or sequencing.

PCR is useful for quantitative analysis of gene expression of entire gene families or signalling networks in arrayed assays.

PCR is frequently the method of choice for genetic engineering involving mutations, truncations or extensions of existing genes.

PCR is a preferred method for high‐thoughput library screens.
Hot Deserts
Authors: Ezcurra Exequiel , Mellink Eric , Martínez‐Berdeja Alejandra
Published: September 2014

Hot deserts occur in two global belts north and south of the equator, at latitudes where calm air and a stable atmosphere dominate. Desert rainfall occurs in the form of highly unpredictable pulses followed by long periods of drought, and many plants and animals are finely adapted to these cycles of abundance and scarcity. Water‐storing succulents and short‐lived ephemeral plants are some of the most common life forms in these highly variable and strongly pulsating environments. In spite of their apparent barrenness, the hot deserts of the world harbour unique and rare biotas with impressive biological adaptations. As a result of evolution in isolation from each other, the world's deserts have high levels of endemism and harbour rare and unique life forms, a fact that makes them ecologically fragile and highly vulnerable to biological extinction.

Key Concepts:

Large deserts occur in the mid‐latitudes of the world, north and south of the equator, where the atmosphere is highly stable and calm air dominates.

Smaller rain shadow deserts often develop in the leeward side of mountain ranges, which capture moisture before it reaches the downwind side.

Coastal fog deserts, such as Atacama or the Namib, owe their aridity to cold ocean currents, and their moisture oscillates with oceanic ‘El Niño’ cycles.

A panoply of morphological and physiological adaptations have evolved in desert environments, which allow plants and animals to survive the harsh desert conditions.

Some plants store water in fleshy tissues, others develop extremely long roots to tap water in the deep soil aquifer, while others simply die as the drought sets‐in and survive long periods in the form of seed.

Animals may migrate into areas where rain has fallen, and have a complex set of morphological and physiological traits that allows them to regulate their temperature without losing water.

The harsh conditions of deserts have promoted the evolution of a complex set of positive relations among desert organisms, such as ‘nurse’ plants, and elaborate pollination and seed dispersal interactions.
Species Problem – A Philosophical Analysis
Authors: Richards Richard A
Published: September 2014

The ‘species problem’ is that there are multiple ways to conceive species that divide up biodiversity in inconsistent ways. Monistic responses to the species problem seek a single universal species concept, no single concept seems adequate though. Pluralistic responses recognise multiple species concepts, based on differences across biodiversity, theoretical interests or the functioning of concepts. But if what counts as a species taxon depends on human interests it isn't clear that species concepts divide biodiversity into real units and ‘cut nature at its joints’ in a straightforward way. The reality of species also seems to depend on their metaphysical status: what basic kinds of things are they? Some argue that species are sets of organisms, based on real essences, clusters of properties or historical relations. Others argue that they are spatiotemporally restricted individuals analogous to organisms.

Key Concepts:

The species problem is the use of multiple inconsistent species concepts that divide biodiversity in different ways.

Monism is the view that correctly understood, there is only one kind of species thing.

Natural kinds are groupings that are independent of human conventions and preferences, and are studied by science.

Pluralism is the view that there are two or more kinds of species things.

Pragmatic pluralism is the view that organisms can be grouped into species on the basis of different research interests.

Realism is the view that species taxa are real and independent of human conventions.

The species‐as‐individuals thesis is that species are historical individuals with beginnings, endings, change over time and cohesion. Organisms are ‘parts’ of a species.

The species‐as‐sets thesis is that species are sets of organisms, where set inclusion is determined by intrinsic or extrinsic properties. Organisms are ‘members’ of a species.
Ethics of Research: Protection of Human Subjects
Authors: Gifford Fred
Published: September 2014

Medical research involving human subjects is invaluable for answering both scientific and clinical questions, notably those centred on making medical intervention as effective and safe as possible. But it raises a number of difficult moral issues: such experimentation can impose risk, questions arise about the adequacy of informed consent, and clinical research creates a tension between the roles of clinical therapist and research scientist. Many of these are encapsulated in the various regulations that exist – this article focuses on the guidelines for the United States – so part of what is required to be an ethical researcher is an understanding of these regulations, but it also requires ethical reasoning about such issues as informed consent, confidentiality, randomisation, placebos, vulnerable populations and special issues that arise in research across national boundaries.

Key Concepts:

A data and safety monitoring board (DSMB) is a committee set up for a given trial, independent from the researchers, which monitors (unblended) data as they accumulate, so as to make judgements about changes in the study including recommending early termination of the study.

Informed consent is the fundamental (legal and ethical) requirement that a human subject give his or her voluntary and informed consent before being subject to research.

An institutional review board (IRB) is a committee given the responsibility for approving or rejecting research protocols to be carried out within a given institution (such as a hospital or university).

Randomized clinical trials (RCTs) are studies where participants are assigned by chance to receive one or another clinical intervention, thus controlling for the effect of other variables.

Equipoise is the situation where there is no way to judge the difference between values of the different arms of a clinical trial, and it is often said that this must obtain to ensure the ethical acceptabilty of the trial.
Stored Human Bodily Material: Use in Research in the United Kingdom
Authors: Skene Loane
Published: September 2014

Human bodily material can be removed from a living person and stored and used in research if the person has been informed about the storage and use of the material in research, and consented. If the person is a child (under 18), or not competent to consent, a parent or other lawfully authorised person may consent. Similarly, a lawfully authorised representative may consent for an adult who is not competent to consent. People, or their nominated representatives, may authorise the use of bodies or bodily material after death, for research. Bodily material removed for diagnostic or treatment procedures, or kept for audit or forensic testing, may be used in research without consent if a recognised research ethics committee has approved the research and the material is provided in unidentifiable form.

Key Concepts:

Human bodily material from a living person may be used in research if the person consents to its use in research.

A parent or legally authorised representative may be able to consent if the person is a child and not able to do consent; and a legally authorised representative may be able to consent for an adult who is not competent to consent.

Consent does not need to be in writing but the person should be provided with written or verbal information about the proposed research before consenting.

A person or the person's nominated representative may consent to the use of the person's body or bodily material in research after the person's death.

If the bodily material was initially removed for a purpose other than research, such as a diagnostic test, treatment, an audit or a forensic test, it can be used in research if consent can be obtained later; or in limited circumstances without consent, if it is unidentifiable; a recognised research ethics committee (REC) has approved the project; and, in England, Wales and Northern Ireland, but not Scotland, a licence has been obtained from the Human Tissue Authority.

People do not legally ‘own’ bodily material removed from their body. They have no legal right to have the material returned to them; used only in a particular way or destroyed. However, under ethical guidelines, bodily material should not be used in research if people are known to object.
Philosophy of Biological Classification
Authors: Richards Richard A
Published: September 2014

Biological classification is natural in that all cultures classify life, and humans acquire classifications as they learn the general terms in a language. This tendency is reflected in the Linnaean hierarchy that has dominated biological classification for the last several centuries. Even as this hierarchy has become entrenched though, there are enduring disputes about biological classification. First is metaphysical, the nature of biological categories. Are they natural kinds, historical kinds or historical individuals? Second are the theoretical bases and operational procedures. What should a biological classification represent, and how should it be constructed? Third are the nature and value of tree thinking, and the implications that has for the formal classificatory framework. If a classification is to represent the evolutionary tree in all its complexity, it is not clear that the Linnaean hierarchy and its nomenclature will be adequate.

Key Concepts:

The theoretical basis of a classification is what it represents.

The formal structure of a classification involves the organisation of the categories.

The operational procedures of a classification are the rules for generating the classification.

An evolutionary tree is a branching diagram that represents at minimum the branching order of evolution.

Nomenclature is the naming system for the categories in a classification.
Evolutionary History of the Proviruses
HERV
‐K 113 and
HERV
‐K 115
Authors: Garrison Keith E , Nixon Douglas F , Pillai Satish K , Jha Aashish R
Published: September 2014

Human endogenous retroviruses are found throughout the genome, and most insertions predate human divergence from other primates. A small number are unique to humans and unfixed in the human genome. Much scientific interest has centered on the human endogenous retroviruses (HERV)‐K113 and HERV‐K115 insertions. The evolutionary history of these two endogenous proviruses is complex, and the estimates of both of their insertion times have recently been revised. HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 million years ago (Ma), while HERV‐K115 was inserted into the genome sometime between 1.1 and 1.9 Ma. Both insertions occurred during a time when

Homo erectus

is believed to have been the dominant hominin species.

Key Concepts:

HERV‐K113 and HERV‐K115 are members of the HML‐2 group of endogenous retroviruses and neither insertion is fixed in the modern human genome.

Despite their unfixed state, HERV‐K113 and HERV‐K115 are not recent insertions into the human genome.

HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 Ma.

HERV‐K115 inserted into the genome sometime between 1.1 and 1.9 Ma.

Despite a possibly wide separation in their insertion times, HERV‐K113 and HERV‐K115 are highly similar in sequence.

Both insertions occurred during a time when
Homo erectus
is believed to have been the dominant hominin species.
Molecular Genetics of 21‐Hydroxylase Deficiency
Authors: Parajes Silvia , Krone Nils
Published: September 2014

Steroid 21‐hydroxylase deficiency (21OHD) accounts for approximately 95% of cases of congenital adrenal hyperplasia, one of the most common inherited metabolic disorders. It can be clinically classified into classic and nonclassic 21OHD. Classic 21OHD is associated with glucocorticoid deficiency and, in 46,XX patients, with disorder of sex development. Mineralocorticoid synthesis may also be significantly impaired in two‐thirds of patients, leading to life‐threatening salt‐wasting (SW) crises. Nonclassic 21OHD is milder and presents mainly with hyperandrogenism. 21OHD is caused by mutations in the
CYP21A2
gene. The vast majority of
CYP21A2
mutations are a result of unequal crossing overs and gene conversions with its highly homologous pseudogene,
CYP21A1P
. Molecular genetic analysis is challenging and requires the combination of different methods to detect gene deletions, chimeric genes, gene duplications and point mutations. An overall good genotype–phenotype correlation exists for the SW phenotype. Therefore, molecular diagnosis of 21OHD complements clinical diagnosis and allows for clinical and genetic counselling.

Key Concepts:

Steroid 21‐hydroxylase deficiency (21OHD) is an autosomal recessive disorder caused by mutations in the
CYP21A2
gene and represents the most common form of congenital adrenal hyperplasia.

A good genotype–phenotype correlation exists for the mineralocorticoid deficiency phenotype.

Although a trend exists, the severity of 46,XX disorder of sex development as well as of other hyperandrogenic signs and symptoms correlates less strongly with the
CYP21A2
genotype.

Common pseudogene‐derived mutations account for the majority of 21OHD disease‐causing alleles; these include gene deletions, chimeric genes, seven single point mutations, an 8 base‐pair deletion and a cluster of three point mutations.

Molecular genetic analysis of the
CYP21A2
gene is challenging due to the high‐sequence homology with its pseudogene (
CYP21A1P
), the high rate of large rearrangements with different break points, and the presence of complex alleles carrying various mutations.

Some less common mutations are highly prevalent in specific populations due to founder effects. These should be considered in the genetic diagnosis of 21OHD when only screening for otherwise common
CYP21A2
mutations.

CYP21A2
gene duplications should be considered in carriers of the p.Gln318X mutation to provide the correct molecular genetic diagnosis.

Molecular genetic diagnosis is essential to provide the correct diagnosis and allows for appropriate clinical and genetic counselling.
Cannabinoids and the Brain
Authors: Alexander Stephen PH
Published: September 2014

The cannabinoid system in the brain is targetted in the use and abuse of preparations from the
Cannabis
plant. This system is composed of synthetic enzymes for the endogenous lipid‐derived ligands, the cannabinoid receptors they activate and the enzymes which transform them. These endocannabinoids are amides, such as anandamide, or esters, such as 2‐arachidonoylglycerol, whose primary target in the central nervous system is the CB
1
cannabinoid receptor, a G protein‐coupled receptor expressed to unusually high levels. Δ
9
‐Tetrahydrocannabinol (THC) appears to be the sole psychoactive entity present in
Cannabis
plant, which elicits the characteristic responses in man and animals. The pharmacology and biochemistry of the endocannabinoid system has been thoroughly investigated since the identification of CB
1
cannabinoid receptors. As yet, however, the translation of this knowledge into a clinical setting has been of limited success.

Key Concepts:

Δ
9
‐Tetrahydrocannabinol appears to be the major psychoactive agent present in the
Cannabis
plant.

Δ
9
‐Tetrahydrocannabinol acts as a partial agonist at the CB
1
cannabinoid receptor.

CB
1
cannabinoid receptors appear to be the most densely expressed G protein‐coupled receptors in the brain.

CB
1
cannabinoid receptors couple functionally to an inhibition of transmitter release.

CB
2
cannabinoid receptors are primarily associated with the immune system, but may also be found in the CNS.

Endogenous cannabinoids, termed endocannabinoids, are fatty acid derivatives.

Endocannabinoids are not stored in vesicles, but rather are made on demand.

Endocannabinoid production is involved in two neurophysiological phenomena, termed depolarisation‐evoked suppression of excitation (DSE) and depolarisation‐evoked suppression of inhibition (DSI).

Endocannabinoids may also act at particular ligand‐gated ion channels (notably the TRPV1 vanilloid receptor) and nuclear hormone receptors (notably peroxisome proliferator‐activated receptors).
Genetics of Preterm Birth
Authors: Lengyel Candice , Muglia Louis J , Pavličev Mihaela
Published: September 2014

The control of normal birth timing in mammals and the fundamental signals that initiate preterm birth in humans are critical areas of scientific investigation. Preterm birth is the leading cause of infant mortality throughout the world, and the single greatest challenge in women's and children's health today. Despite the recognised importance of this area of investigation, relatively limited advances have been made. In part, this limited success in revealing mechanisms results from divergence in the endocrine physiology of pregnancy between species. To have an effect on these biological and medical gaps in knowledge, new genetic studies in humans and comparative genomic investigations across species have been undertaken. In this article, the authors summarise the current status of genetic and genomic approaches to elucidate the control of birth timing.

Key Concepts:

Genetic factors, primarily in the maternal genome, contribute to preterm birth risk.

The physiology of human pregnancy differs from other species except for other higher primates.

Humans have unique constraints for birth timing related to foetal size and/or metabolism.

Candidate gene association studies have not been generally informative.

New data emerging from non‐biased genome‐wide approaches have suggested new pathways for birth timing and preterm birth risk.
Molecular Genetics of Human Congenital Limb Malformations
Authors: Pickering Joseph , Towers Matthew
Published: September 2014

Congenital limb malformations are observed in approximately 1 in 500 people making them one of the most frequent birth defects. Increasing numbers of genes are being identified that when functionally perturbed result in human limb abnormalities. The functions of many of these genes have been investigated in the two main models of limb development – the chick and the mouse. Limb defects are often part of complex syndromes that affect other structures in the body. This reflects the multiple roles that many genes play during embryonic development. Recently, an emerging theme is that the disruption of
cis
‐regulatory enhancers controlling expression of important developmental genes can lead to limb‐specific birth defects. Future research focusing on how the human limb develops will increase our understanding of the molecular and genetic basis of congenital defects.

Key Concepts:

Chick and mouse embryology has contributed to our knowledge of limb development and the basis of human limb defects.

Many key patterning genes found in mouse and chick research cause human limb defects when mutated.

Limb defects are often part of complex syndromes.

Defects which affect only the limb are often caused by disruption of
cis
‐regulatory enhancers.

Future work on how the human limb develops will further our understanding of congenital defects.
Genetics of Neonatal Autoimmune and Autoinflammatory Diseases
Authors: Bachove Inessa , Chang Christopher
Published: September 2014

Genetic predisposition has been widely studied in autoimmune and autoinflammatory diseases and has been found to play a significant role in pathogenesis, although the environment, including dietary habits, chemicals and hygienic conditions have been postulated to influence expression of these diseases as well. The autoimmune diseases most prevalent in the newborn include neonatal lupus and neonatal antiphospholipid antibody syndrome. The diseases are characterised by maternal antibodies to SS‐A (Ro) and SS‐B (La). The genetics underlying these diseases have been found to involve both HLA and non‐HLA associations. The neonatal autoinflammatory diseases include the cryopyrin‐associated periodic syndromes (CAPS), of which familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and neonatal onset multisystem inflammatory diseases (NOMID) are the three distinct phenotypes resulting from mutations in the
CIAS
1 gene (
NLRP3
gene). The gene mutation in CAPS are gain‐of‐function mutation of the NLRP3 gene coding for cryopyrin, resulting in dysfunctional inflammasomes. A defect in the inflammasome leads to overproduction of interleukin‐1, resulting in inflammatory symptoms seen in CAPS. Understanding the genetics responsible for neonatal lupus, neonatal antiphospholipid antibody syndrome and CAPS may drive future research into an elucidation of complex pathophysiologic mechanisms of these diseases and perhaps ultimately lead to better treatment modalities.

Key Concepts:

Diseases that involve immune dysfunction in the neonate include neonatal autoimmune and autoinflammatory conditions, along with the more well‐defined immunodeficiency syndromes.

The genetics of neonatal autoimmunity and neonatal autoinflammatory syndromes are very different.

In addition to a genetic component, the pathogenesis of these two groups of diseases may also involve an epigenetic and environmental component.

The presence of a common genetic defect may result in different clinical phenotypes, as illustrated by the three CAPS syndromes.

Treatment of these diseases is dependent on an increased knowledge of the pathogenesis of these diseases.

Genetic counselling is an important component of the management of these diseases.
Sequencing Strategies and Tactics inDNAandRNAAnalysis
Authors: Azhikina Tatyana L.
Published: September 2014

The primary structure of nucleic acids is a key not only to physical and chemical properties of the molecules but also to the biological (genetic) information therein, including structures of genes and proteins, the ways of gene regulation and cell response to different signals. Sequencing procedures are aimed at the determination of sequences of monomer units constituting linear biopolymer molecules, DNA or RNA residues in case of nucleic acids.

This article reviews existing sequencing strategies: different approaches of random or systematic sequencing applicable to long and unique DNA fragments, including entire genomes; massive sequencing of relatively short fragments such as RNAs and complementary DNAs (cDNAs); and comparative sequencing of related DNA fragments originating from various individuals or different species.
Tip‐enhanced
R
aman Spectroscopy
Authors: Gibson Kirsty F. , Kazarian Sergei G.
Published: September 2014

Tip‐enhanced Raman spectroscopy (TERS) is a powerful analytical technique for chemical analysis at the nanoscale. Three different SPM/TERS (scanning probe microscopy/tip‐enhanced Raman spectroscopy) modes allow the analysis of a wide range of samples. TERS has been shown to be of great use in materials‐based applications, particularly for nanostructured materials and in the analysis of biologically relevant systems. In this article, the fundamentals and theoretical aspects of TERS, the instrumentation required to perform a TERS experiment, and examples of a range of practical applications are discussed.