bluuebunny/crossref_metadata_2025 huggingface dataset:
Combating corruption in a microfinance institution
Authors: Azim Mohammad I. , Sheng Kuang , Barut Meropy
Published: April 2017

Purpose

Combatting corruption is an important social and commercial issue in most human societies. Many researchers have revealed how an effective anti-corruption practice can possibly minimise corruption in an organisation. However, studies focusing on organisations which are relatively successful in managing corruption at the employee level are relatively rare. On this note, this study aims to focus on Grameen Bank in particular, a Nobel-Prize-winning microfinance institute that was able to minimise its level of corruption among its employees in a country where corruption is the norm.

Design/methodology/approach

This paper uses standard economic theory to explain the perceptions and behaviours of the employees of Grameen Bank who live and work in a highly corrupt socio-cultural environment. This paper used questionnaires to ascertain the perceptions of Grameen Bank employees’ notions regarding corruption-combating behaviours. Interviews were also conducted among Grameen’s board members, managers and officers to further explore the nature and effectiveness of this organisation’s anti-corruption mechanisms.

Findings

Corruption can never be entirely eradicated; however, it can be diminished and opportunities for corruption can be minimised. This paper found, through an analysis of employees’ perceptions relating to governance and corruption in the Grameen Bank, that corruption exists, but there are systems in place to prevent it and to assist with staff morality. This research also uncovered a number of best practices in Grameen Bank’s governance to minimise corrupt behaviours, which include, but are not limited to, strong monitoring, decentralisation of authority, review of decision-making process, high internal audit intensity, impersonal punishment, anti-corruption cultures and transparency.

Originality/value

This study suggests that it is possible for organisations to resist corruption, especially microfinance institutions, even when they operate in a highly corrupt socio-cultural environment.
Drivers of species' role in avian seed‐dispersal mutualistic networks
Authors: Sebastián‐González Esther
Published: April 2017

The mutualistic interaction between frugivore birds and the fruiting plants they disperse presents an asymmetric interaction pattern, with some species having a more important role (i.e. being essential) for maintaining the structure and functioning of the interaction network. The identification of the biological characteristics of these species is of major importance for the understanding and conservation of seed‐dispersal interactions.

In this study, I use a network approach and avian seed‐dispersal networks from 23 different geographical areas to test five hypotheses about species characteristics determining the structure of the assemblage.

I expected (i) large birds to forage on a large number of fruits and (ii) large fruits to be dispersed by few bird species (because of morphological constraints), and (iii) highly energetic fruits to be dispersed by more bird species (in accordance with optimal foraging theory). Besides the number of interacting partners, I also expected (iv) large birds and (v) small energetic fruits to be important for the maintenance of the structure of the interactions in seed‐dispersal networks. As species that are closely related are more likely to be similar to each other, I performed phylogenetically corrected analyses to account for this data dependence.

Although bird size was not associated to species important in the maintenance of the structure of the seed‐dispersal community, I identified that bird species whose diet was strongly dependent on fruits were important for the structure of the network. Regarding the plants, I found that large fruits were dispersed by fewer species, but the most important attribute to predict the role of a fruit was its energy content (higher energy, more bird species dispersing the plant, but low‐energy fruits being of conservation concern because they are dispersed by specific species).

The results of this study suggest that the role of the species in seed‐dispersal assemblages seems to be determined by the role of the species as consumers (frugivory degree for animals) or by their nutritional inputs (energy content for fruits) rather than by morphological constrains.
Increasing adolescents' depth of understanding of cross‐curriculum words: an intervention study
Authors: Spencer Sarah , Clegg Judy , Lowe Hilary , Stackhouse Joy
Published: April 2017

Background

There is some evidence that vocabulary intervention is effective for children, although further research is needed to confirm the impact of intervention within contexts of social disadvantage. Very little is known about the effectiveness of interventions to increase adolescent knowledge of cross‐curriculum words.

Aims

To evaluate the effectiveness of an intervention programme designed to develop adolescents’ knowledge of cross‐curriculum words.

Methods & Procedures

Participants were 35 adolescents aged between 12 and 14 years who were at risk of educational underachievement with low scores on a range of assessments. Participants received a 10‐week intervention programme in small groups, targeting 10 cross‐curriculum words (e.g., ‘summarize’). This was evaluated using a bespoke outcome measure (the Word Knowledge Profile). The study involved an AABA design, with a repeated baseline, delayed intervention cohort and blind assessment. Intervention included both semantic and phonological information about the target words and involved the adolescents using the words in multiple contexts.

Outcomes & Results

Results were promising and participants’ knowledge of the targeted words significantly increased following intervention. Progress was demonstrated on the Word Knowledge Profile on the item requiring participants to define the word (for the summer intervention group only). This increase in depth of knowledge was seen on taught words but not on matched non‐taught words.

Conclusions & Implications

Cross‐curriculum words are not consistently understood by adolescents at risk of low educational attainment within a low socio‐economic context. A 10‐week intervention programme resulted in some increases to the depth of knowledge of targeted cross‐curriculum words.
Grammaticality differences between Spanish‐speaking children with specific language impairment and their typically developing peers
Authors: Jackson‐Maldonado Donna , Maldonado Ricardo
Published: April 2017

Background

A limited number of studies have analyzed grammaticality in monolingual Spanish‐speaking children with specific language impairment (SLI). Most of the available data are based on bilingual speakers.

Aims

To extend previous studies by doing a more detailed analysis of grammatical types in monolingual Spanish‐speakers with and without SLI.

Methods & Procedures

Forty‐nine Spanish‐speaking children (18 with SLI, 17 age‐matched typically developing controls, 14 language‐matched controls) were recruited from schools in Mexico and observed in a spontaneous narrative task.

Outcomes & Results

The findings were inconsistent with those of previous studies. Significant differences were found for article, connector and preposition omissions, and the per cent of ungrammatical utterances. There were no significant differences found for clitics and verb phrases, though clitic substitutions were frequent. Language‐matched controls did not produce different frequencies of ungrammatical utterances.

Conclusions & Implications

Significant differences were found for three main items: the per cent of ungrammatical utterances, the omission of articles and the omission of prepositions. Therefore, we propose these components be taken into consideration when distinguishing typically developing children from children with SLI.
Evaluation of an interview skills training package for adolescents with speech, language and communication needs
Authors: Mathrick Rachel , Meagher Tina , Norbury Courtenay Frazier
Published: April 2017

Background & Aims

We evaluated a structured intervention programme aimed at preparing adolescents with developmental language disorders for job interviews. Our primary outcome measures included change in ratings of verbal and non‐verbal social communication behaviours evident during mock interviews.

Methods & Procedures

In study 1, 12 participants, aged 17–19 years, from a specialist sixth‐form college completed the intervention and two mock interviews, one pre‐ and one post‐intervention. In study 2, 34 participants, aged 17–19 years, completed a modified intervention programme and three mock interviews, one at baseline (included to control for possible practise effects), one pre‐ and one post‐intervention. In both studies, interviews were video recorded and social communication behaviours were coded by independent assessors blind to interview time, participant diagnosis and therapy content. A repeated‐measures design was employed to measure change in communication behaviours.

Outcomes & Results

In study 1, a significant increase in the number of ‘positive’ verbal and non‐verbal social communication behaviours was observed from pre‐ to post‐intervention. However, there was no significant change in the number of ‘negative’ behaviours (i.e., fidgeting, irrelevant remarks). In study 2, there were no significant changes in verbal behaviours, but significant group differences (though wide individual variation) in both positive and negative non‐verbal social communication behaviours.

Conclusions & Implications

Our findings suggest that training specific social communication skills that are important for interview success, and consistently reinforcing those behaviours during therapy practice, can increase the use of those skills in an interview setting, though in this heterogeneous population there was considerable variation in therapy outcome. The skills of the interviewer were identified as a potential source of variation in outcome, and a target for future research and practice.
Keeping out and getting in: reframing emergency department gatekeeping as structural competence
Authors: Buchbinder Mara
Published: April 2017

Sociologists have tended to frame medical gatekeeping as an exclusionary social practice, delineating how practitioners and clerical staff police the moral boundaries of medicine by keeping out patients who are categorised as ‘bad’, ‘deviant’, or otherwise problematic. Yet medical gatekeeping, understood more broadly, can include not only keeping patients out of particular clinical settings, but also redirecting them to alternative sources of care. In this article, I draw on qualitative analysis of audio‐recorded patient‐provider interactions in a United States emergency department (ED) to illustrate medical gatekeeping as a two‐step process of, first, categorising certain patient complaints as unsuitable for treatment within a particular setting, and second, diverting patients to alternative sites for care. I refer to these as the restrictive and facilitative components of medical gatekeeping to denote how each relates to patients’ access to care, recognising that both components of medical gatekeeping are part of a coordinated organisational strategy for managing resource scarcity. By illustrating how ED providers reveal intimate knowledge of structural vulnerabilities in diverting socioeconomically disadvantaged patients with chronic back pain to clinical sites that are better equipped to provide care, I suggest that we rethink the emphasis on restrictive practices in sociological accounts of medical gatekeeping.
Evaluation of high‐intensity focused ultrasound ablation for uterine fibroids: an IDEAL prospective exploration study
Authors: Chen J , Li Y , Wang Z , McCulloch P , Hu L , Chen W , Liu G , Li J , Lang J ,   Committee of the Clinical Trial of HIFU versus Surgical Treatment for Fibroids
Published: April 2017

Objective

To evaluate the clinical outcomes of high‐intensity focused ultrasound (HIFU) and surgery in treating uterine fibroids, and prepare for a definitive randomised trial.

Design

Prospective multicentre patient choice cohort study (IDEAL Exploratory study) of HIFU, myomectomy or hysterectomy for treating symptomatic uterine fibroids.

Setting

20 Chinese hospitals.

Population or sample

2411 Chinese women with symptomatic fibroids.

Methods

Prospective non‐randomised cohort study with learning curve analysis (IDEAL Stage 2b Prospective Exploration Study).

Main outcome measures

Complications, hospital stay, return to normal activities, and quality of life (measured with UFS‐Qol and SF‐36 at baseline, 6 and 12 months), and need for further treatment. Quality‐of‐life outcomes were adjusted using regression modelling. HIFU treatment quality was evaluated using LC‐CUSUM to identify operator learning curves. A health economic analysis of costs was performed.

Results

1353 women received HIFU, 472 hysterectomy and 586 myomectomy. HIFU patients were significantly younger (P < 0.001), slimmer (P < 0.001), better educated (P < 0.001), and wealthier (P = 0.002) than surgery patients. Both UFS and QoL improved more rapidly after HIFU than after surgery (P = 0.002 and P = 0.001, respectively at 6 months), but absolute differences were small. Major adverse events occurred in 3 (0.2%) of HIFU and in 133 (12.6%) of surgical cases (P < 0.001). Median time for hospital stay was 4 days (interquartile range, 0–5 days), 10 days (interquartile range, 8–12.5 days) and 8 days (interquartile range, 7–10 days).

Conclusions

HIFU caused substantially less morbidity than surgery, with similar longer‐term QoL. Despite group baseline differences and lack of blinding, these findings support the need for a randomised controlled trial (RCT) of HIFU treatment for fibroids. The IDEAL Exploratory design facilitated RCT protocol development.

Tweetable abstract

HIFU had much better short‐term outcomes than surgery for fibroids in 2411‐patient Chinese IDEAL format study.
Does Corporate Social Responsibility (CSR) Create Shareholder Value? Evidence from the Indian Companies Act 2013
Authors: MANCHIRAJU HARIOM , RAJGOPAL SHIVARAM
Published: April 2017

In 2013, a new law required Indian firms, which satisfy certain profitability, net worth, and size thresholds, to spend at least 2% of their net income on corporate social responsibility (CSR). We exploit this regulatory change to isolate the shareholder value implications of CSR activities. Using an event study approach coupled with a regression discontinuity design, we find that the law, on average, caused a 4.1% drop in the stock price of firms forced to spend money on CSR. However, firms that spend more on advertising are not negatively affected by the mandatory CSR rule. These results suggest that firms voluntarily choose CSR to maximize shareholder value. Therefore, forcing a firm to spend on CSR is likely to be sub‐optimal for the firm with a consequent negative impact on shareholder value.
Impact of emergency department discharge stream short stay unit performance and hospital bed occupancy rates on access and patient flowmeasures: A single site study
Authors: Shetty Amith L , Teh Caleb , Vukasovic Matthew , Joyce Shannon , Vaghasiya Milan R , Forero Roberto
Published: April 2017

Objective

The ED discharge stream short stay units (EDSSUs) aim to facilitate patient flows through EDs. We investigate the relationship between EDSSU census and hospital bed occupancy rates (BORs) on National Emergency Access Target (NEAT) performance and did‐not‐wait (DNW) rates at a tertiary metropolitan adult ED in Sydney, Australia.

Methods

We collated data for all ED presentations between 1 January 2012 and 31 December 2014. Daily ED, EDSSU census and ED‐accessible hospital BORs were tabulated with daily ED NEAT performance and DNW rates. Non‐parametric regression analyses was conducted on cohorts of appropriate, inappropriate, successful and failed EDSSU admissions based on local admission policies and BOR for NEAT and DNW outcomes.

Results

Among all presentations (n = 192 506) during the study period, 43.8% of patients were admitted in hospital including 10.4% for EDSSU (n = 20 081). Analyses reveal modest positive correlation of EDSSU admissions with NEAT performance (τ = 0.35, P < 0.001) and weak negative correlation with DNW rates (τ = −0.29, P < 0.001). These associations were more pronounced on days when BOR >100% (τ = 0.39 and τ = −0.36, P < 0.001). BOR of >100% were associated with reduced EDSSU admits, NEAT performance and increased DNW rates (P < 0.001). Appropriate EDSSU admissions had shorter EDSSU length of stay than inappropriate EDSSU admissions (350 vs 557 min, median difference −158 min, P < 0.001).

Conclusion

Appropriate use of EDSSU provides effective conduit for ongoing patients’ management beyond mandated timelines. Health systems should focus on reducing hospital BORs to mitigate exclusive ED pressure to deliver NEAT performance targets.
Hospital use in Aboriginal and non‐Aboriginal patients with chronic disease
Authors: Whyatt David , Yap Matthew , Tenneti Raji , Pearson Glenn , Vickery Alistair
Published: April 2017

Objective

The objective of this study was to compare rates of hospital utilisation in Aboriginal and non‐Aboriginal peoples before and after hospital admission for chronic obstructive pulmonary disease, heart failure and/or type 2 diabetes mellitus.

Methods

This was a longitudinal cohort study from 2002 to 2014, which was conducted in all hospitals in Western Australia. The participants of this study were Aboriginal and non‐Aboriginal patients with a principal diagnosis of heart failure, type 2 diabetes or chronic obstructive pulmonary disease, on admission to hospital, where such an event had not occurred in the previous 3 years. Inpatient days and ED presentations were the main outcome measures.

Results

Among the patients with chronic disease, Aboriginal people have similar inpatient days for all causes compared to non‐Aboriginal people. However, they have much higher ED presentations in comparison. Age of onset of cardinal events occurs 15–20 years earlier in Aboriginal patients with chronic disease. Although age has little influence on ED presentations in non‐Aboriginal chronic disease patients, younger Aboriginal people with chronic disease present far more often to ED than older Aboriginal people.

Conclusions

Aboriginal people use health services in a different manner when compared to non‐Aboriginal people. In a subset of patients with chronic disease, high use may be reduced with better access to primary healthcare. Policy‐makers and healthcare providers should examine healthcare use from primary to tertiary care among the Aboriginal population, with a particular focus on ED presentations; investigate the underlying causes driving specific patterns of health service utilisation among Aboriginal people; and develop interventions to reduce potential deleterious impacts, and enhance the potential benefits, of specific patterns of healthcare use.
Dietary Tuna Dark Muscle Protein Attenuates Hepatic Steatosis and Increases Serum High‐Density Lipoprotein Cholesterol in Obese Type‐2 Diabetic/Obese KK‐Ay Mice
Authors: Maeda Hayato , Hosomi Ryota , Fukuda Mari , Ikeda Yuki , Yoshida Munehiro , Fukunaga Kenji
Published: April 2017

Tuna muscle consists of light and dark muscle in approximately equal proportions. However, besides for the light muscle of tuna, cod, sardine, and salmon, few researches have assessed the health‐promoting functions of fish protein. Therefore, we evaluated the mechanisms underlying the alteration of lipid storage and cholesterol metabolism following the intake of tuna dark muscle protein (TDMP) by obese type‐2 diabetic/obese mice. Four‐week‐old male KK‐Ay mice were separated into 2 dietary groups, with one group receiving a casein‐based diet and the other receiving a diet with the substitution of part of the protein (50%, w/w) by TDMP (TDMP diet) for 4 wk. The TDMP diet significantly increased the content of serum high‐density lipoprotein cholesterol, partly due to the reduction of the expression of scavenger receptor class B member 1 in epididymal white adipose tissue. In addition, dietary TDMP decreased the content of hepatic triacylglycerol, which could be due to the enhancement of carnitine palmitoyltransferase‐2 activity through the activation of the expression of the peroxisome proliferative activated receptor‐α in the liver. These results suggest that TDMP could have the potential to prevent the development of obesity‐related diseases by suppressing the storage of hepatic triacylglycerol and cholesterol.
How abnormal is binge eating? 18‐Year time trends in population prevalence and burden
Authors: Mitchison D. , Touyz S. , González‐Chica D. A. , Stocks N. , Hay P.
Published: April 2017

Objective

Although findings suggest that binge eating is becoming increasingly normative, the ‘clinical significance’ of this behaviour at a population level remains uncertain. We aimed to assess the time trends in binge‐eating prevalence and burden over 18 years.

Method

Six cross‐sectional face‐to‐face surveys of the Australian adult population were conducted in 1998, 2005, 2008, 2009, 2014, and 2015 (Ntotal = 15 126). Data were collected on demographics, 3‐month prevalence of objective binge eating (OBE), health‐related quality of life, days out of role, and distress related to OBE.

Results

The prevalence of OBE increased six‐fold from 1998 (2.7%) to 2015 (13.0%). Health‐related quality of life associated with OBE improved from 1998 to 2015, where it more closely approximated population norms. Days out of role remained higher among participants who reported OBE, although decreased over time. Half of participants who reported weekly (56.6%) and twice‐weekly (47.1%) OBE reported that they were not distressed by this behaviour. However, the presence of distress related to OBE in 2015 was associated with greater health‐related quality‐of‐life impairment.

Conclusion

As the prevalence of binge eating increases over time, associated disability has been decreasing. Implications for the diagnosis of disorders associated with binge eating are discussed.
Behavioural addiction and substance addiction should be defined by their similarities not their dissimilarities
Authors: Griffiths Mark D.
Published: April 2017

Commentary to: How can we conceptualize behavioural addiction without pathologizing common behaviours?
Attributes of the complete dental record: a Delphi approach to standards
Authors: Amos KJ , Cockrell DJ , Palermo C , Rosehill S , Bearman M
Published: April 2017

Background

Adherence to the Dental Board of Australia Guidelines on dental records is not universal and remediation of deficient practise requires clarity in the practical application of standards. The aim of this research is to clarify practical requirements of dental record keeping in New South Wales.

Methods

Seventeen experts were invited to participate in an electronically administered series of Delphi questionnaires. Concepts were refined until consensus was reached.

Results

Two rounds were required to achieve a satisfactory level of consensus (>80%). A high level of consensus was obtained across the two rounds, with 72% and 86% agreement on propositions in the first and second rounds, respectively. Consensus criteria were established in 14 domains to establish attributes of the complete dental record (ACDR).

Conclusions

The ACDR may supplement existing national guidelines and are likely to be useful in a remediation context in which clear, unambiguous expectations for conduct are paramount.
Total thyroidectomy for pressure symptoms in patients with Hashimoto's thyroiditis
Authors: Heggie Katrina , Yeung Meei , Grodski Simon , Lee James , Serpell Jonathan
Published: April 2017

Background

Hashimoto's thyroiditis (HT) is rarely on its own the indication for thyroidectomy. However, surgery in patients with HT will be undertaken when there is malignancy and may be required for pressure symptoms. Therefore, this study aimed to investigate the indications for surgery in HT patients.

Methods

The Monash University Endocrine Surgery Database was analysed from 1994 to 2013 for patients with HT. Patients with HT were compared to a similar group of patients with no HT on histopathology. Patient demographics, indication for surgery, histopathology, gland weight and complications were analysed.

Results

A total of 2346 patients underwent total thyroidectomy during the study period. The median age was 55 years. Eleven percent of patients had HT on final pathology (259/2346). HT patients reported more pressure symptoms, 25.5% compared to those with other pathology, 18.9% (P = 0.01). Patients with pressure symptoms had heavier glands, 113 g compared to 85 g in those with other indications for surgery (P = 0.048). Within the HT cohort, the median gland weight was 66 g compared to 93 g in those without HT (P < 0.01). On multivariate analysis, pressure symptoms as an indication for surgery was associated with HT (P < 0.01), but age, gender and gland weight were not associated. In patients operated for pressure with HT as the only pathology, 90% had relief of pressure symptoms.

Conclusion

Patients with HT were more likely to have pressure symptoms as an indication for surgery independent of gland weights.
Associating Liver Partition and Portal vein ligation for Staged hepatectomy after pre‐operative chemotherapy
Authors: Vondran Florian W. R. , Oldhafer Felix , Ringe Kristina I. , Wirth Thomas C. , Kleine Moritz , Jäger Mark D. , Klempnauer Juergen , Bektas Hueseyin
Published: April 2017

Background

Recently a procedure termed ‘Associating Liver Partition and Portal vein ligation for Staged hepatectomy’ (ALPPS) was developed to increase the resectability of marginally resectable or locally unresectable liver tumours. This study focused on the application of ALPPS in patients with advanced colorectal liver metastases (CRLM) and pre‐operative chemotherapy, with the aim to investigate whether the latter still allows for sufficient hypertrophy of the future liver remnant (FLR) following the first step of ALPPS.

Methods

Retrospective analysis was performed on six patients suffering from advanced CRLM. Analyses comprised demographical and basic clinical data, the perioperative courses as well as short‐ and long‐term outcomes.

Results

All patients presented with bilobular CRLM and pre‐operative chemotherapy of at least 6 months. Extended right hemihepatectomy was performed in all cases, four patients additionally received atypical resections in segments II/III. Mean FLR prior to step 1 of ALPPS was 397.9 cm3 (121–753 cm3), on average representing 20.9% of the total liver volume (13.2–27.1%). A mean hypertrophy of the FLR of 67.9% (32.5–94.1%) was achieved. Overall, severe morbidity (Dindo Clavien >3a) occurred in two patients. Following completion of ALPPS, mean post‐operative disease‐free survival was 5.7 months (2.6–8.9 months).

Conclusion

Despite pre‐operative chemotherapy, ALPPS seems to result in adequate liver hypertrophy, preventing post‐operative small‐for‐size syndrome. However, there might be a high risk of tumour recurrence in patients with an aggressive tumour biology.
Central venous catheters and biofilms: where do we stand in 2017?
Authors: Gominet Marie , Compain Fabrice , Beloin Christophe , Lebeaux David
Published: April 2017

The use of central venous catheters (CVC) is associated with a risk of microbial colonization and subsequent potentially severe infection. Microbial contamination of the catheter leads to the development of a microbial consortia associated with the CVC surface and embedded in an extracellular matrix, named biofilm. This biofilm provides bacterial cells the ability to survive antimicrobial agents and the host immune system and to disseminate to other sites of the body. The best preventive strategy is to avoid any unnecessary catheterization or to reduce indwelling duration when a CVC is required. Beside aseptic care and antibiotic‐impregnated catheters (like minocycline/rifampin), preventive locks can be proposed in some cases, whereas non‐biocidal approaches are under active research like anti‐adhesive or competitive interactions strategies. When the diagnosis of catheter‐related bloodstream infection (CRBSI) is suspected on clinical symptoms, it requires a microbiological confirmation by paired blood cultures in order to avoid unnecessary catheter removal. The treatment of CRBSI relies on catheter removal and systemic antimicrobials. However, antibiotic lock technique (ALT) can be used as an attempt to eradicate biofilm formed on the inside lumen of the catheter in case of uncomplicated long‐term catheter‐related BSI caused by coagulase‐negative staphylococci (CoNS) or Enterobacteriaceae. Recently, promising strategies have been developed to improve biofilm eradication; they rely on matrix degradation or destabilization or the development of anti‐persister compounds, targeting the most tolerant bacterial cells inside the biofilm. Understanding biofilm formation at the molecular level may help us to develop new approaches to prevent or treat these frequent infections.
Microenvironmental characteristics and physiology of biofilms in chronic infections of CF patients are strongly affected by the host immune response
Authors: Jensen Peter Ø. , Kolpen Mette , Kragh Kasper N. , Kühl Michael
Published: April 2017

In vitro studies of Pseudomonas aeruginosa and other pathogenic bacteria in biofilm aggregates have yielded detailed insight into their potential growth modes and metabolic flexibility under exposure to gradients of substrate and electron acceptor. However, the growth pattern of P. aeruginosa in chronic lung infections of cystic fibrosis (CF) patients is very different from what is observed in vitro, for example, in biofilms grown in flow chambers. Dense in vitro biofilms of P. aeruginosa exhibit rapid O2 depletion within <50–100 μm due to their own aerobic metabolism. In contrast, in vivo investigations show that P. aeruginosa persists in the chronically infected CF lung as relatively small cell aggregates that are surrounded by numerous PMNs, where the activity of PMNs is the major cause of O2 depletion rendering the P. aeruginosa aggregates anoxic. High levels of nitrate and nitrite enable P. aeruginosa to persist fueled by denitrification in the PMN‐surrounded biofilm aggregates. This configuration creates a potentially long‐term stable ecological niche for P. aeruginosa in the CF lung, which is largely governed by slow growth and anaerobic metabolism and enables persistence and resilience of this pathogen even under the recurring aggressive antimicrobial treatments of CF patients. As similar slow growth of other CF pathogens has recently been observed in endobronchial secretions, there is now a clear need for better in vitro models that simulate such in vivo growth patterns and anoxic microenvironments in order to help unravel the efficiency of existing or new antimicrobials targeting anaerobic metabolism in P. aeruginosa and other CF pathogens. We also advocate that host immune responses such as PMN‐driven O2 depletion play a central role in the formation of anoxic microniches governing bacterial persistence in other chronic infections such as chronic wounds.
Biofilms in orthopedic infections: a review of laboratory methods
Authors: Dibartola Alex C. , Swearingen Matthew C. , Granger Jeffrey F. , Stoodley Paul , Dusane Devendra H.
Published: April 2017

Bacterial infection after hardware implantation in orthopedic surgery is a devastating issue as it often necessitates increased hospital costs and stays, multiple revision surgeries, and prolonged use of antibiotics. Because of the nature of hardware implantation into the body, these infections are commonly in the form of attached biofilms. The current literature on a range of methodologies to study clinically explanted infected orthopedic hardware, with potential biofilm, in the laboratory setting is limited. General methods include traditional and advanced culturing techniques, microscopy imaging techniques, and techniques that manipulate genetic material. The future of diagnostic techniques for infected implants, innovative hardware design, and treatment solutions for patients all depend on the successful evaluation and characterization of clinical samples in the laboratory setting. This review provides an overview of current methods to study biofilms associated with orthopedic infections and insight into future directions in the field.
Antibiotic treatment of biofilm infections
Authors: Ciofu Oana , Rojo‐Molinero Estrella , Macià María D. , Oliver Antonio
Published: April 2017

Bacterial biofilms are associated with a wide range of infections, from those related to exogenous devices, such as catheters or prosthetic joints, to chronic tissue infections such as those occurring in the lungs of cystic fibrosis patients. Biofilms are recalcitrant to antibiotic treatment due to multiple tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm infections in spite of antibiotic exposure which predisposes to antibiotic resistance development (genetic resistance). Understanding the interplay between phenotypic and genetic resistance mechanisms acting on biofilms, as well as appreciating the diversity of environmental conditions of biofilm infections which influence the effect of antibiotics are required in order to optimize the antibiotic treatment of biofilm infections. Here, we review the current knowledge on phenotypic and genetic resistance in biofilms and describe the potential strategies for the antibiotic treatment of biofilm infections. Of note is the optimization of PK/PD parameters in biofilms, high‐dose topical treatments, combined and sequential/alternate therapies or the use antibiotic adjuvants.
Biofilms and host response – helpful or harmful
Authors: Moser Claus , Pedersen Hannah Trøstrup , Lerche Christian Johann , Kolpen Mette , Line Laura , Thomsen Kim , Høiby Niels , Jensen Peter Østrup
Published: April 2017

Biofilm infections are one of the modern medical world's greatest challenges. Probably, all non‐obligate intracellular bacteria and fungi can establish biofilms. In addition, there are numerous biofilm‐related infections, both foreign body‐related and non‐foreign body‐related. Although biofilm infections can present in numerous ways, one common feature is involvement of the host response with significant impact on the course. A special characteristic is the synergy of the innate and the acquired immune responses for the induced pathology. Here, we review the impact of the host response for the course of biofilm infections, with special focus on cystic fibrosis, chronic wounds and infective endocarditis.
Antifouling and antimicrobial biomaterials: an overview
Authors: Francolini Iolanda , Vuotto Claudia , Piozzi Antonella , Donelli Gianfranco
Published: April 2017

The use of implantable medical devices is a common and indispensable part of medical care for both diagnostic and therapeutic purposes. However, as side effect, the implant of medical devices quite often leads to the occurrence of difficult‐to‐treat infections, as a consequence of the colonization of their abiotic surfaces by biofilm‐growing microorganisms increasingly resistant to antimicrobial therapies. A promising strategy to combat device‐related infections is based on anti‐infective biomaterials that either repel microbes, so they cannot attach to the device surfaces, or kill them in the surrounding areas. In general, such biomaterials are characterized by antifouling coatings, exhibiting low adhesion or even repellent properties towards microorganisms, or antimicrobial coatings, able to kill microbes approaching the surface. In this light, the present overview will address the development in the last two decades of antifouling and antimicrobial biomaterials designed to potentially limit the initial stages of microbial adhesion, as well as the microbial growth and biofilm formation on medical device surfaces.
Microbiological diagnosis of device‐related biofilm infections
Authors: Xu Yijuan , Larsen Lone Heimann , Lorenzen Jan , Hall‐Stoodley Luanne , Kikhney Judith , Moter Annette , Thomsen Trine Rolighed
Published: April 2017

Medical device‐related infections cause undue patient distress, increased morbidity and mortality and pose a huge financial burden on healthcare services. The pathogens are frequently distributed heterogeneously in biofilms, which can persist without being effectively cleared by host immune defenses and antibiotic therapy. At present, there is no ‘gold standard’ available to reveal the presence of device‐related biofilm infections. However, adequate sample collection and logistics, standardised diagnostic methods, and interpretation of results by experienced personnel are important steps in efficient diagnosis and treatment of these infections. The focus of this mini review is on prosthethic joint and cardiovascular implantable device infections, which exemplify permanent devices that are placed in a sterile body site. These device‐related infections represent some of the most challenging in terms of both diagnosis and treatment.
In vitro studies evaluating the effects of biofilms on wound‐healing cells: a review
Authors: Kirker Kelly R. , James Garth A.
Published: April 2017

Chronic wounds are characterized as wounds that have failed to proceed through the well‐orchestrated healing process and have remained open for months to years. Open wounds are at risk for colonization by opportunistic pathogens. Bacteria that colonize the open wound bed form surface‐attached, multicellular communities called biofilms, and chronic wound biofilms can contain a diverse microbiota. Investigators are just beginning to elucidate the role of biofilms in chronic wound pathogenesis, and have simplified the complex wound environment using in vitro models to obtain a fundamental understanding of the impact of biofilms on wound‐healing cell types. The intent of this review is to describe current in vitro methodologies and their results. Investigations started with one host cell‐type and single species biofilms and demonstrated that biofilms, or their secretions, had deleterious effects on wound‐healing cells. More complex systems involved the use of multiple host cell/tissue types and single species biofilms. Using human skin‐equivalent tissues, investigators demonstrated that a number of different species can grow on the tissue and elicit an inflammatory response from the tissue. A full understanding of how biofilms impact wound‐healing cells and host tissues will have a profound effect on how chronic wounds are treated.
Chronic urinary tract infections in patients with spinal cord lesions – biofilm infection with need for long‐term antibiotic treatment
Authors: Tofte Nete , Nielsen Alex C. Y. , Trøstrup Hannah , Andersen Christine B. , Von Linstow Michael , Hansen Birgitte , Biering‐Sørensen Fin , Høiby Niels , Moser Claus
Published: April 2017

Patients suffering from spinal cord injuries resulting in complete or incomplete paraplegia or tetraplegia are highly disposed to frequent, recurrent or even chronic urinary tract infections (UTIs). The reason for the increased risk of acquiring UTIs is multifactorial, including reduced sensation of classical UTI symptoms, incomplete bladder emptying, frequent catheterizations or chronic urinary tract catheters. Biofilms in relation to UTIs have been shown both on catheters, on concrements or as intracellular bacterial communities (IBCs). Due to the increased risk of acquiring recurrent or chronic UTIs and frequent antibiotic treatments, patients experience an increased risk of being infected with antibiotic‐resistant bacteria like extended‐spectrum β‐lactamase–producing Escherichia coli or Klebsiella spp., but also bacteria like Pseudomonas aeruginosa inherently resistant to several antibiotics. Diagnosing the UTI can also be challenging, especially distinguishing harmless colonization from pathogenic infection. Based on a previous study showing activation of humoral immune response toward UTI pathogens in patients with spinal cord lesions (SCL), the present mini review is an evaluation of using antibody response as an indicator of chronic biofilm UTI. In addition, we evaluated the effect of long‐term treatment with antibiotics in patients with SCLs and chronic UTI, defined by culturing of a uropathogen in the urine and elevated specific precipitating antibodies against the same uropathogen in a blood sample. Elimination of chronic UTI, decrease in specific precipitating antibody values and avoiding selection of new multidrug‐resistant (MDR) uropathogens were the primary markers for effect of treatment. The results of this evaluation suggest that the long‐term treatment strategy in SCL patients with chronic UTI may be effective; however, randomized prospective results are needed to confirm this.
A short history of microbial biofilms and biofilm infections
Authors: Høiby Niels
Published: April 2017

The observation of aggregated microbes surrounded by a self‐produced matrix adhering to surfaces or located in tissues or secretions is old since both Leeuwenhoek and Pasteur have described the phenomenon. In environmental and technical microbiology, biofilms, 80–90 years ago, were already shown to be important for biofouling on submerged surfaces, for example, ships. The concept of biofilm infections and their importance in medicine was, however, initiated in the early 1970s by the observation of heaps of Pseudomonas aeruginosa cells in sputum and lung tissue from chronically infected cystic fibrosis patients. The term biofilm was introduced into medicine in 1985 by J. W. Costerton. During the following decades, the number of published biofilm articles and methods for studying biofilms increased rapidly and it was shown that adhering and nonadhering biofilm infections are widespread in medicine. The medical importance of biofilm infections is now generally accepted and guidelines for prophylaxis, diagnosis, and treatment have been published.
Orthopaedic biofilm infections
Authors: Zimmerli Werner , Sendi Parham
Published: April 2017

Many infections of the musculoskeletal system are biofilm infections that develop on non‐living surfaces. Microorganisms adhere either on dead bone (sequesters) or implants. As a rule for a curative concept, chronic osteomyelitis or implant‐associated bone infection must be treated with a combination of surgery and antimicrobial therapy. If an implant is kept in place, or a new device is implanted before complete healing of infection, a biofilm‐active antibiotic should be used. Rifamycins are active against biofilms of staphylococci, and fluoroquinolones against those of Gram‐negative bacilli. In this review, the management of chronic osteomyelitis, periprosthetic joint infection and implant‐associated osteomyelitis of long bones is presented.
Dental biofilm infections – an update
Authors: Larsen Tove , Fiehn Nils‐Erik
Published: April 2017

Teeth are colonized by oral bacteria from saliva containing more than 700 different bacterial species. If removed regularly, the dental biofilm mainly comprises oral streptococci and is regarded as resident microflora. But if left undisturbed, a complex biofilm containing up to 100 bacterial species at a site will build up and may eventually cause development of disease. Depending on local ecological factors, the composition of the dental biofilm may vary considerably. With access to excess carbohydrates, the dental biofilm will be dominated by mainly gram‐positive carbohydrate‐fermenting bacteria causing demineralization of teeth, dental caries, which may further lead to inflammation and necrosis in the pulp and periapical region, i.e., pulpitis and periapical periodontitis. In supra‐ and subgingival biofilms, predominantly gram‐negative, anaerobic proteolytic bacteria will colonize and cause gingival inflammation and breakdown of supporting periodontal fibers and bone and ultimately tooth loss, i.e., gingivitis, chronic or aggressive periodontitis, and around dental implants, peri‐implantitis. Furthermore, bacteria from the dental biofilm may spread to other parts of the body by bacteremia and cause systemic disease. Basically, prevention and treatment of dental biofilm infections are achieved by regular personal and professional removal of the dental biofilm.
Diagnosis of biofilm infections in cystic fibrosis patients
Authors: Høiby Niels , Bjarnsholt Thomas , Moser Claus , Jensen Peter Østrup , Kolpen Mette , Qvist Tavs , Aanæs Kasper , Pressler Tanja , Skov Marianne , Ciofu Oana
Published: April 2017

Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex‐mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix. Specific PNA‐FISH probes can be used to identify P. aeruginosa and other pathogens in situ in the biofilms. Growth of mucoid colonies from the locations mentioned above is also diagnostic for biofilm infection. Rise of specific anti‐P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung infection, sIgA in saliva or nasal secretions in case of paranasal sinus infection. Similar approaches have been developed to diagnose chronic biofilm infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex.
Platelets: much more than bricks in a breached wall
Authors: Mancuso Maria Elisa , Santagostino Elena
Published: April 2017

Platelets have various roles in vascular biology and homeostasis. They are the first actor in primary haemostasis and play important roles in thrombosis pathogenesis, but they are also part of innate immunity, which initiates and accelerate many inflammatory conditions. In some contexts, their immune functions are protective, while in others they contribute to adverse inflammatory outcomes. Platelets express numerous receptors and contain hundreds of secretory molecules that are crucial for platelet functional responses. The capacity of platelets to produce and secrete cytokines, chemokines and related molecules, under the control of specific intracellular pathways, is intimately related to their key role in inflammation. They are also able to intervene in tissue regeneration and repair because they produce pro‐angiogenic mediators. Due to this characteristic platelets are involved in cancer progression and spreading. In this review we discuss the complex role of platelets, which bridges haemostasis, inflammation and immune response both in physiological and pathological conditions.