Expert Reviews in Molecular Medicine launches ‘Discovery’ section

ERM Cover final

Expert Reviews in Molecular Medicine launches ‘Discovery’ section and welcomes original research under a gold Open Access extension.

We have launched the ‘Discovery’ section within our journal Expert Reviews in Molecular Medicine (ERMM) and now welcome high-quality, innovative original research papers to complement its authoritative ‘Reviews’ section. Authors who wish to publish their papers in ‘ERMM: Discovery’ will be able to do so under a gold Open Access model and payment of an article processing charge (APC). Reviews will continue to be accessed via a subscription to ERMM, with Open Access as an option for Review authors to choose should they wish to pay the APC.

ERMM has been publishing high-quality peer-refereed review articles since late 1997, which have proved a valuable forum for authoritative reviews in the area of molecular medicine. The Journal has an impressive Impact Factor of 6.628 (2012), which places it in a strong position amongst its competitors and this expansion will provide readers and authors with an enhanced resource for molecular medicine research.

ERMM: Discovery will be overseen and edited by Dr Julian Sale who will be working alongside the Editor-in-Chief, Professor Timothy Cox.

“We are delighted that Cambridge University Press has decided to enrich its portfolio of contemporary biological science by taking this publication initiative; it will incorporate new pages of experimental research to synergise with Expert Reviews. We welcome this innovative step and greatly look forward to receiving fresh discovery science in molecular medicine for competitive publication.”

Molecular medicine as a broad definition refers to elucidating the pathogenesis of disease at the molecular or physiological level, which may lead to the design of specific tools for disease diagnosis, treatment or prevention – this highlights the timeliness and importance of the Journal in the field. ERMM: Discovery will publish original work from across the full breadth of molecular medicine and pathology. Its scope mirrors that of ERMM: Reviews focussing on the molecular mechanisms of disease, diagnostics and therapy. The Journal particularly invites original research papers which provide mechanistic insights, while papers of a purely descriptive or correlative nature and case reports are unlikely to be accepted unless they provide exceptional scientific insight.

The Editors are inviting high-quality contributions of original research for ERMM: Discovery andreview papers for ERMM: Reviews. For detailed instructions on how to prepare your submission, please see our Instructions for Contributors.

Content from Expert Reviews in Molecular Medicine can be viewed atjournals.cambridge.org/erm. A subscription will be required to access Review articles but all Discovery articles will be freely available under an OA license and are not included in the subscription price. All Open Access articles in this journal have article level metrics available.

Football focus: A study into preparedness of the health sector in Brazil for the 2014 FIFA World Cup

brazil world cup

This post is taken from the abstract of the paper “Hospital Preparedness in Advance of the 2014 FIFA World Cup in Brazil” published in Prehospital and Disaster Medicine.

Regardless of the capacity of the health care system of the host nation, mass gatherings require special planning and preparedness efforts within the health system. Brazil will host the 2014 Fédération Internationale de Football Association (FIFA) World Cup and the 2016 Olympics. This paper represents the first results from Project ‘‘Prepara Brasil,’’ which is investigating the preparedness of the health sector and pharmaceutical services for these events.

This study was designed to identify the efforts taken to prepare the health sector in Brazil for the FIFA World Cup 2014 event, as well as the 2016 Summer Olympics.

Key informant interviews were conducted with representatives of both the municipality and hospital sectors in each of the 12 host cities where matches will be played. A semi-structured key informant interview guide was developed, with sections for each type of participant. One of each municipality’s reference hospitals was identified and seven additional general hospitals were randomly selected from all of the inpatient facilities in each municipality. The interviewers were instructed to contact a reference hospital, and two of the other hospitals, in the jurisdiction for participation in the study.

Questions were asked about plans for mass-gathering events, the interaction between hospitals and government officials in preparation for the World Cup, and their perceptions of their surge capacity to meet the potential demands generated by the presence of the World Cup events in their municipalities.

In all, 11 representatives of the sampled reference hospitals, and 24 representatives of other general private and public hospitals in the municipalities, were interviewed.

Most of the hospitals had some interaction with government officials in preparation for the World Cup 2014. Approximately one-third (34%) received training activities from the government. Fifty-four percent (54%) of hospitals had no specific plans for communicating with the government or other agencies during the World Cup. Approximately half (51%) had plans for surge capacity during the event, but only 27% had any surge capacity for isolation of potentially infectious patients.

Overall, although there has been mention of a great deal of planning on the part of the government officials for the World Cup 2014, hospital surge to meet the potential increase in demand still falls short.

 

The full paper “Hospital Preparedness in Advance of the 2014 FIFA World Cup in Brazil” can be viewed free of charge for a limited time here.

 

Does the Baby-Friendly Hospital Initiative increase breastfeeding?

The July Nutrition Society Paper of the Month is from Public Health Nutrition and is entitled ‘Evaluating the impact of the Baby-Friendly Hospital Initiative on breast-feeding rates: a multi-state analysis’.

PHN NS POM image

Not only does breastfeeding improve the health of mothers and infants, but it also reduces health care costs and has a smaller environmental footprint than formula-feeding. Although currently three-quarters of US women start breastfeeding, women with lower education are much less likely to try. One known barrier is the lack of breastfeeding support that women receive in the hospital.

The Baby-Friendly Hospital Initiative (BFHI) was developed by the World Health Organization and UNICEF in 1991 to promote, protect, and support breastfeeding within the birth facility and after. While more than 20,000 hospitals and birth centers in 156 countries have been designated as Baby-Friendly, there are only 182 BFHI facilities in the US in 43 states and DC. Despite the success of the BFHI on breastfeeding practices internationally, research in the US has been limited. We wanted to determine whether the BFHI increased breastfeeding overall and, particularly, whether it improved breastfeeding among women with lower education.

Using data from 5 states, we compared breastfeeding outcomes between 11,723 mothers who gave birth in 13 BFHI hospitals and 13,604 mothers from 19 non-BFHI birth facilities. Although overall women who gave birth in BFHI hospitals were no more likely to start or continue breastfeeding than women from non-BFHI facilities, we showed that it benefited women with lower education. Only 78% of women with a high school degree or less started breastfeeding, but we found that those women who delivered in BFHI hospitals were 3.8 percentage points more likely to start breastfeeding than women with the same educational attainment who delivered in non-BFHI facilities. In contrast, 90% of women with more than a high school degree started breastfeeding, but giving birth in a BFHI hospital did not further increase their likelihood of starting or continuing breastfeeding.

What are the implications of these findings?

Women with low education benefited the most from giving birth in Baby-Friendly hospitals, suggesting that the BFHI may be one way to help decrease socio-economic disparities in breastfeeding. Currently only 7% of births in the US are in BFHI facilities. Our results support the recommendation to increase the number of BFHI-accredited birth facilities to encourage women to start breastfeeding, but more may be needed to help women continue breastfeeding after discharge.

This paper is freely available for one month via the following link: journals.cambridge.org/ns/jul14

The journey of a medical book – from concept to completion….

Book Binding

Weekend Book Binding. Photo: Nate Steiner. Used under CreativeCommons.

Since our book has been published, colleagues, friends and family have been intrigued as to our journey to publication. For us, it is immensely satisfying to see, and feel, the final product. It is also a good time for us to reflect on how we got here…

 

As with many of these things, the book’s concept was spawned during a chance conversation between operating theatre lists. We were colleagues at a busy DGH and in the midst of our FRCA exams – Ned lining up for the primary written, and Marc for the final written. ‘Wouldn’t it be great,’ Ned mused, ‘if there was one book where all the equations for the exams were collated, explained and made sense of’. A quick Google search revealed no such texts, and thus we returned to our revision relying on the time-honoured tradition of thumbing through dog-eared text books and trusting our sage superiors’ tuition. This initial conversation had however planted somewhat of a seed for an idea and following a quick straw poll of our colleagues, we surmised that equations were one of the aspects that really exorcised FRCA candidates.

 

The next stage was to articulate our thoughts, and we decided that the best way to do this was to use a publisher’s guidelines. Having both used, and been thoroughly impressed with Cross & Plunketts’ Physics, Pharmacology and Physiology for Anaesthetists, we approached Cambridge University Press (CUP) with the opinion that our text could be a natural bed-fellow to said text.

Having browsed the FRCA curriculum, and documented every equation we came across in our revision texts, we collated the list of all the equations encountered, wrote a number of example chapters, and submitted our book proposal to CUP. A swift and very positive peer review ensued, and we were delighted, though somewhat surprised to have our idea accepted.

One important caveat had been proposed, the suggestion that we used a well-established senior colleague to both edit the text, and mentor us through the writing stages. One such colleague independently sprung to both our minds, Dr Wynne Davies. Having both worked under Wynne’s clinical guidance, his immense knowledge and ever enthusiastic willingness to teach made him the ideal candidate. This was bolstered further as Wynne had also previously been an examiner for the Royal College of Anaesthetists, such that he was ideally placed to provide ideas and opinions from ‘the other side of the table’. Thankfully he accepted, and we are both extremely grateful for all the hard work, mentorship and friendship that he has provided us with over the months of writing.

 

With the proposal accepted and contracts signed, the hard work started. The submission deadline clock had started ticking, with completion some 18 months away. Our approach to writing was to do quasi peer-review. Together we formatted a page template, decided on the format of each chapter, and subsequently divided the topics and started writing. Dropbox (other internet clouds are available) was used to store the drafted pages, thus enabling the other author (Marc for Ned, Ned for Marc) to review and edit each person’s initial endeavours. Following the undertaking of these preliminary corrections, Wynne edited each page in turn, before once again returning each to us for universal approval.

Ensuring accuracy was a top priority, as was making the book readable, relevant and clear. Arguably the most time consuming part of writing was providing the applications of each equation to clinical practice. However, this, apart from having all the equations necessary for the examinations in one place, is what we feel that the USP of our book is. Knowing the equations is one thing; understanding them and being able to derive them another. Being able to apply the equations to medical and anaesthetic practice is vital in order to negotiate the examinations, particular the oral ones, and also arguably to stay sane whilst revising and questioning the need to learn and memorise some rather obtuse concepts.

Once the text was prepared and bounced between us until we were happy with it, we sent it to Cambridge University Press for proof-reading and type-setting. It was fascinating to be involved in these processes and again, an eye for detail was mandatory. We also had our non-anaesthetist partners look over it which was invaluable.

At last the text was ready and we waited in anticipation for the final product: it was a great feeling of satisfaction when it fell through the letterbox and made all the hard work worthwhile.

 

Whilst neither of us were deluded enough to think that writing a book would be easy, one should certainly not underestimate the amount of time, effort and sacrifice required. Writing, reading, editing and re-revising comments was somewhat time consuming, especially alongside a PhD (Ned), and HEMS & NHS England Fellowship (Marc).

Moving forwards, we eagerly await peoples’ feedback. Undoubtedly as medicine and anaesthetics progresses, there will be corrections and clarifications required in future editions. We very much hope that readers will enjoy it and find it useful and we would welcome any comments and feedback.

In the book, we have tried hard, and hopefully succeeded in the majority of cases to tick all the boxes which will give readers a head start, whether they are preparing for the examinations themselves, helping others to do so, or even, dare we say it, examining!

Top tips amassed from 18 months of toil…

  1. Know your audience and write for them, not you.
  2. Choose a mentor that you trust and can reply on.
  3. Know your market and spot the gaps. They may be very obvious such that one assumes someone else has already filled them.
  4. Don’t underestimate the amount of work involved, and ensure that your nearest and dearest are supportive of your project!
  5. Detail, detail, detail…edit, edit, edit.

Dr Marc Wittenberg and Dr Edward Gilbert-Kawai are co-authors of Essential Equations for Anaesthesia (out now).

Essential Equations for Anaesthesia

 

Mind over matter

Family Fun

The June International Psychogeriatrics Article of the Month is entitled ‘Mind over matter – what do we know about neuroplasticity in adults?’ by Vyara Valkanova, Rocio Eguia Rodriguez and Klaus P. Ebmeier

 

Until recently the capacity of the human brain for structural and functional reorganization (brain plasticity) was considered to be limited to critical periods during development. Neuroimaging provides a non-invasive window into the living brain and has been used to study different aspects of brain plasticity during the learning of new skills or after novel experiences. We reviewed the strongest neuroimaging evidence for experience-dependent plasticity in adult humans, and therefore focused on longitudinal studies only (i.e. participants are scanned before and after different interventions, and then the images are compared).

We identified 36 studies that employed different types of training, such as juggling, exercising working memory, meditation, learning abstract information (studying for exams), and aerobic exercise. Although different patterns of results were found, there was consistent evidence that the brain (gray as well as white matter – brain cells as well as neuronal connections) retains much greater plasticity in adults (<75 years old) than is traditionally thought.

Before such research results can be translated into medical practice, there are many questions that still need to be answered. We currently do not know enough about the type and duration of the interventions that are effective, about the upper limits of improvement, how gains can be maintained, and most importantly the exact relationship between structural change and functional improvement. Further, all reviewed studies are in healthy individuals, while the impact of such interventions in patients with dementia is less well studied.

Future research will need to include larger samples and standardised training protocols to allow comparison of studies done at different research centres. Animal studies combining imaging with histological studies [detailed microscopic analysis] can be very useful in understanding the cellular mechanisms underlying learning, which is important when devising effective interventions. Finally, a multimodal imaging approach, where measures derived from complementary imaging modalities is likely to play a major role in increasing our understanding of brain plasticity. It is possible today, for example, to examine the volume of brain grey matter, the quality of anatomical connections between different areas of the brain and the degree of cooperation between different regions of the brain during the same examination, in other words to examine structural and functional brain connectivity. We know now that even the adult brain has a significant potential to change and compensate for any damage, for example after a stroke. Research in this area will have important implications for our ability to harness the natural self-healing and compensation properties of our brains to the greatest effect, in neurodegenerative diseases such as the dementias.

 

The full paper “Mind over matter – what do we know about neuroplasticity in adults?” is available free of charge for a limited time here.

The commentary on the paper, “Expanding the mind – growing the brain…” is also available free of charge for one month here.

 

The relationship between C-RP and delirium and its severity

shutterstock_140571478

The May International Psychogeriatrics Article of the Month is entitled ‘The association between C-reactive protein and delirium in 710 acute elderly hospital admissions’ by C.W. Ritchie, T.H. Newman, B. Leurent and E.L. Sampson.

Delirium is a common but poorly understood condition that primarily affects elderly patients; it is defined as having an acute onset and fluctuating course with deficits in attention, arousal state and perception and is associated with poor outcomes. The burden delirium places on the healthcare system will only increase as the ageing population grows, which means improvements in prediction, diagnosis and management are necessary. Whilst peripheral inflammation is a recognized precipitant of delirium, and evidence supports a neuroinflammatory basis, the role that the inflammatory marker C-reactive protein (C-RP) plays has not been defined. C-RP is regularly measured and is raised in many conditions which are associated with delirium however studies investigating C-RP’s relationship with delirium show contrasting results.

Our study took a large population of elderly patients who were admitted to hospital after presenting acutely and investigated the relationship between C-RP and delirium. Published in the May edition of International Psychogeriatrics the article describes the finding that C-RP was associated with delirium independent of other risk factors but not with delirium severity. On sub-group analysis this association remained in those patients who suffered musculoskeletal problems such as fractures and traumatic injuries. To our knowledge this was the largest study to date which investigated this relationship in a general elderly population.

These observations suggest that C-RP may represent a major factor in the genesis of delirium secondary to musculoskeletal damage. Additionally C-RP could act as a marker for current or incipient delirium and as such may form part of a risk score to aid recognition of at risk patients. Importantly it must be noted that longitudinal studies are necessary in order to establish a timeline to this relationship.

Furthermore this study adds weight to the neuroinflammatory hypothesis underlying delirium genesis and proposes that whilst C-RP may be important in musculoskeletal cases it is unlikely to be part of a unifying pathway leading to the common end point that is delirium. Future studies should investigate this relationship as well as other inflammatory mediators to further our understanding of delirium.

 

The full paper “The association between C-reactive protein and delirium in 710 acute elderly hospital admissions” is available free of charge for a limited time here.

The commentary on the paper, “Delirium really matters” is also available free of charge for one month here.

Psychiatric Genetic Revolution – is calcium the key?

DNA Rendering. Photo: ynse. used under CretaiveCommons

DNA Rendering. Photo: ynse. used under CreativeCommons

Dr. Berrettini and I published Principles of Psychiatric Genetics in late 2012. Since then, there have been several interesting developments in Psychiatric Genetics worth calling your attention to. The first is a set of articles from the Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC). The PGC has revolutionized the field of psychiatric genetics in the last decade by bringing together investigators from around the world to pool their carefully collected clinical samples in order to provide the numbers for powerful analyses of common gene variants in major psychiatric disorders such as schizophrenia and bipolar disorder. Whereas the original genome-wide association studies in psychiatry included ~1000 cases and 1000 controls, we are now able to amass collections of 25,000 cases with schizophrenia and 37,000 controls because investigators have come together under the PGC umbrella. This has provided the power to detect more than 100 common single gene variants associated with schizophrenia.

The particular article I wanted to feature was one from the Cross-Disorder Group in that consortium (Cross-Disorder Group of the PGC, Lancet, 2013). Samples were combined from persons with schizophrenia, bipolar disorder, depression, attention-deficit hyperactivity disorder, and autism. There were four single gene variants that were identified from the group of disorders considered together. The fascinating aspect of this was that two of the four were genes controlling calcium channels in the brain. The investigators were also able to test an entire group of calcium-channel related genes (72 genes in all) and demonstrate that variations in this set of gene markers was associated with vulnerability to these conditions, especially to schizophrenia and bipolar disorder. This is a new finding in psychiatry, and it is potentially very relevant to clinical management of these conditions. Calcium channel abnormalities have been described in these disorders, but this hypothesis was not central to a consideration of the neurobiology of these disorders. Over the past three decades, much more energy has been spent on theories involving neurotransmitters such as serotonin, dopamine, and norepinephrine. However, it may be that calcium channel signaling problems are causal to neurotransmitter variation. Calcium flow into the cell is necessary for cell excitation and signaling. Many of the critical second messenger systems in the cell (which carry a signal within the cell after a neurotransmitter hits its target receptor) are dependent on calcium.

Calcium channel inhibitors are available, and have been used to treat cardiovascular conditions for several decades (e.g., verapamil, nifedipine, nimodipine) . They have also been used to treat psychiatric conditions, with some success, but not consistent success. It may be that these agents must be targeted to specific individuals who demonstrate calcium channel gene abnormalities. Or it may be that newly designed drugs with more subtle effects on calcium activity are needed. In any case, this seems like an important clue with ramifications for our understanding of the biology of these disorders, as well as possible treatment strategies.

Another paper from the same group was published later in 2013 (Lee et al, Nature Genetics). This used a method for analyzing the heritability of medical conditions based on genome-wide data. Even if the power is not adequate to identify all of the gene variants individually, you can use the available information on gene arrays (small plastic chips that contain short sequences from every gene in the genome) to test whether or not you have captured some of the variation or not. It could be that testing every gene in the genome in this way would still not give you much information about diagnosis. This was thought to be the case for several years after these techniques were introduced. Many investigators felt that psychiatric disorders were simply too complex in their inheritance to be analyzed by the gene chips. There was too much “missing heritability” (evidence of inheritance from family studies that was not able to be tracked to variations at the gene level). This recent paper demonstrated convincingly that this idea is not true. The psychiatric disorders are analyzable at the level of individual gene variants and functions. We now can be confident that 25-40% of the reason that one person becomes ill with schizophrenia or major depression or autism while another person does not is related to common genetic variation that can be measured in the laboratory. We don’t yet know what all the pertinent genes do but we can anticipate that the answers will be available to us in the coming years. Part of the answer probably relates to calcium channel genes, as noted above.

There is another set of data from this paper that is tremendously important for our ideas of psychiatric diagnosis. For the past hundred years, we have clearly separated schizophrenia (a chronic disorder) and bipolar disorder (an episodic condition). There are different treatments for these conditions and different expectations for how well people will do in overcoming the symptoms. One of the lessons from the latest round of genetic analyses is that there is substantial overlap in the genetic vulnerability factors for the two disorders. The “covariance” between schizophrenia and bipolar disorder is 25-30%. Therefore we should expect that some of the disruption in neurobiological systems will be the same for the two disorders and some will be different. This is consistent with evidence from genetic linkage studies summarized by my colleague Dr. Berrettini some years ago and it is consistent with recent family studies as well. The new information, though, is more specific regarding the amount of overlap. It suggests that we should consider these two diseases similar in type and origin.

John I. Nurnberger, Jr. is co-editor of Principles of Psychiatric Genetics (out now).

Principles of Psychiatric Genetics

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