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1.  Dental skill mix: a cross-sectional analysis of delegation practices between dental and dental hygiene-therapy students involved in team training in the South of England 
Human Resources for Health  2014;12(1):65.
Research suggests that health professionals who have trained together have a better understanding of one another’s scope of practice and are thus equipped for teamwork during their professional careers. Dental hygiene-therapists (DHTs) are mid-level providers that can deliver routine care working alongside dentists. This study examines patterns of delegation (selected tasks and patients) by dental students to DHT students training together in an integrated team.
A retrospective sample of patient data (n = 2,063) was extracted from a patient management system showing the treatment activities of two student cohorts (dental and DHT) involved in team training in a primary care setting in the South of England over two academic years. The data extracted included key procedures delegated by dental students to DHT students coded by skill-mix of operator (e.g., fissure sealants, restorations, paediatric extractions) and patient demography. χ2 tests were conducted to investigate the relationship between delegation and patient age group, gender, smoking status, payment-exemption status, and social deprivation.
A total of 2,063 patients managed during this period received treatments that could be undertaken by either student type; in total, they received 14,996 treatment procedures. The treatments most commonly delegated were fissure sealants (90%) and restorations (51%); whilst the least delegated were paediatric extractions (2%). Over half of these patients (55%) had at least one instance of delegation from a dental to a DHT student. Associations were found between delegation and patient age group and smoking status (P <0.001). Children under 18 years old had a higher level of delegation (86%) compared with adults of working age (50%) and patients aged 65 years and over (56%). A higher proportion of smokers had been delegated compared with non-smokers (45% cf. 26%; P <0.001).
The findings suggest that delegation of care to DHT students training as a team with dental students, involved significantly greater experience in treating children and adult smokers, and providing preventive rather than invasive care in this integrated educational and primary care setting. The implications for their contribution to dentistry and the dental team are discussed, along with recommendations for primary care data recording.
PMCID: PMC4247654  PMID: 25407478
2.  Whole Exome Sequencing Identifies TTC7A Mutations for Combined Immunodeficiency with Intestinal Atresias 
Combined Immunodeficiency with Multiple Intestinal Atresias (CID-MIA) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects.
We sought to determine the underlying genetic causes of CID-MIA by analyzing the exomic sequence of 5 patients and their healthy direct relatives from 5 unrelated families.
We performed whole exome sequencing on 5 CID-MIA patients and 10 healthy direct family members belonging to 5 unrelated families with CID-MIA. We also performed targeted Sanger sequencing for the candidate gene TTC7A on 3 additional CID-MIA patients.
Through analysis and comparison of the exomic sequence of the individuals from these 5 families, we identified biallelic damaging mutations in the TTC7A gene, for a total of 7 distinct mutations. Targeted TTC7A gene sequencing in 3 additional unrelated patients with CID-MIA revealed biallelic deleterious mutations in two of them, as well as an aberrant splice product in the third patient. Staining of normal thymus showed that the TTC7A protein is expressed in thymic epithelial cells as well as in thymocytes. Moreover, severe lymphoid depletion was observed in the thymus and peripheral lymphoid tissues from two patients with CID-MIA.
We identified deleterious mutations of the TTC7A gene in 8 unrelated patients with CID-MIA and demonstrated that the TTC7A protein is expressed in the thymus. Our results strongly suggest that TTC7A gene defects cause CID-MIA.
Clinical Implications
Damaging mutations in the gene TTC7A should be scrutinized in patients with CID-MIA. Characterization of the role of this protein in the immune system and intestinal development, as well as in thymic epithelial cells may have important therapeutic implications.
PMCID: PMC3759618  PMID: 23830146
Combined Immunodeficiency with Multiple Intestinal Atresias; Tetracopeptide Repeat Domain 7A; Whole Exome Sequencing; Thymus
3.  A Survey of the Perception of Comprehensiveness among Dentists in a Large Brazilian City 
Objectives: To quantitatively identify the perception of dentists regarding comprehensiveness and its domains of “patient welcoming”, “bonding” and “quality of care” in primary dental care settings of a large Brazilian city. Methods: A questionnaire was administered to all dentists comprising the primary health care service to Belo Horizonte with tenured jobs and 40 work hours per week, totalling a population of 207 professionals. The response rate was 90.34%. A pilot test was conducted with 44 dentists working in primary care for at least two years and who did not participate in the main study. Descriptive statistical analysis involved calculating proportions. No confidence intervals were calculated because this was a census study. Results: In most items (79.0%), professionals’ perceptions about the comprehensiveness were overwhelmingly positive. When we stratified the analysis by domain and checked those items about which dentists had a less favourable perception, 22.7% were in the patient welcoming domain, 25.0% were in the bonding domain and 12.5% were in quality of care. Conclusions: Comprehensiveness, as an approach in health care practice, needs to be enhanced, and there is evidence that these dentists are aware of its importance.
PMCID: PMC4025042  PMID: 24743842
comprehensive health care; oral health; primary health care; health personnel
4.  The initial U3 snoRNA:pre-rRNA base pairing interaction required for pre-18S rRNA folding revealed by in vivo chemical probing 
Nucleic Acids Research  2011;39(12):5164-5180.
The synthesis of ribosomal subunits in the nucleolus is a conserved, essential process that results in cytoplasmic ribosomes with precisely processed and folded rRNAs assembled with ribosomal proteins. It has been proposed, but never directly demonstrated, that the U3 small nucleolar RNA (snoRNA), a nucleolar component required for ribosome biogenesis, is a chaperone for pre-18S rRNA folding. To test this, we used in vivo chemical probing with dimethyl sulfate to detect changes in pre-rRNA structure upon genetic manipulation of the yeast, Saccharomyces cerevisiae. Based on changes in nucleotide reactivity, we found that the U3 snoRNA is indeed required for folding of the pre-18S rRNA. Furthermore, we detected a new essential base pairing interaction that is likely the initial anchor that recruits the U3 snoRNA to the pre-rRNA, is a prerequisite for the subsequent interactions, and is required for the small subunit processome formation. Substitution of the 5′-ETS nucleotides of the pre-rRNA involved in this initial base pairing interaction is lethal, but growth is restored when a complementary U3 snoRNA is expressed. The U3 snoRNP, via base pairing, and its associated proteins, are part of the required machinery that orchestrates the folding of pre-rRNA that results in the assembly of the small ribosomal subunit.
PMCID: PMC3130255  PMID: 21349877
5.  Short and long-term career plans of final year dental students in the United Arab Emirates 
BMC Oral Health  2013;13:39.
New dental schools have been established to train dentists in many parts of the world. This study examines the future dental workforce from the first dental school in the United Arab Emirates [UAE]; the aim of this study was to explore the short and long-term career aspirations of the final year dental students in the UAE in relation to their demography.
Final year dental students of the Ajman University’s College of Dentistry (n=87) were invited to participate in a self-completion questionnaire survey. Descriptive analysis, chi-square tests, and binary logistic regression analysis were carried out on career aspirations using SPSS v20.
Eighty-two percent of students (n=71) responded, the majority of whom were female (65%; n=46). Ethnicity was reported as: ‘other Arab’ (61%; n=43), ‘Emirati’ (17%, n=12), and ‘Other’ (21%, n=15). In the short-term, 41% (n=29) expressed a desire to work in government training centres, with Emirati students significantly more likely to do so (p=0.002). ‘Financial stability’ (80%; n=57) and ‘gaining professional experience’ (76%; n=54) emerged as the most important influences on their short-term career plans. The vast majority of students wished to specialise in dentistry (92%; n=65) in the longer term; logistic regression analysis revealed that the odds of specialising in the most popular specialties of Orthodontics and Oral and Maxillofacial Surgery were less for the ‘Other’ ethnic group when compared with ‘Emirati’ students (0.26; 95% CI 0.068-0.989; p=0.04). Almost three-quarters of the students overall (72%; n=51) intended to work full-time. ‘High income/financial security’ (97%; n=69), ‘standard of living’ (97%; n=69), ‘work/life balance’ (94%; n=67), and ‘professional fulfilment’ (87%; n=62) were reported by the students as the most influential items affecting their long-term professional career choices.
The findings suggest that students aspire to make a long-term contribution to the profession and there is a high level of interest in specialisation with a desire to achieve financial stability and quality of life.
PMCID: PMC3751876  PMID: 23937862
Dental student; Career expectations; Dentistry; United Arab Emirates
6.  Optical Spectral Surveillance of Breast Tissue Landscapes for Detection of Residual Disease in Breast Tumor Margins 
PLoS ONE  2013;8(7):e69906.
We demonstrate a strategy to “sense” the micro-morphology of a breast tumor margin over a wide field of view by creating quantitative hyperspectral maps of the tissue optical properties (absorption and scattering), where each voxel can be deconstructed to provide information on the underlying histology. Information about the underlying tissue histology is encoded in the quantitative spectral information (in the visible wavelength range), and residual carcinoma is detected as a shift in the histological landscape to one with less fat and higher glandular content. To demonstrate this strategy, fully intact, fresh lumpectomy specimens (n = 88) from 70 patients were imaged intra-operatively. The ability of spectral imaging to sense changes in histology over large imaging areas was determined using inter-patient mammographic breast density (MBD) variation in cancer-free tissues as a model system. We discovered that increased MBD was associated with higher baseline β-carotene concentrations (p = 0.066) and higher scattering coefficients (p = 0.007) as measured by spectral imaging, and a trend toward decreased adipocyte size and increased adipocyte density as measured by histological examination in BMI-matched patients. The ability of spectral imaging to detect cancer intra-operatively was demonstrated when MBD-specific breast characteristics were considered. Specifically, the ratio of β-carotene concentration to the light scattering coefficient can report on the relative amount of fat to glandular density at the tissue surface to determine positive margin status, when baseline differences in these parameters between patients with low and high MBD are taken into account by the appropriate selection of threshold values. When MBD was included as a variable a priori, the device was estimated to have a sensitivity of 74% and a specificity of 86% in detecting close or positive margins, regardless of tumor type. Superior performance was demonstrated in high MBD tissue, a population that typically has a higher percentage of involved margins.
PMCID: PMC3724737  PMID: 23922850
7.  Advancing Optical Imaging for Breast Margin Assessment: An Analysis of Excisional Time, Cautery, and Patent Blue Dye on Underlying Sources of Contrast 
PLoS ONE  2012;7(12):e51418.
Breast conserving surgery (BCS) is a recommended treatment for breast cancer patients where the goal is to remove the tumor and a surrounding rim of normal tissue. Unfortunately, a high percentage of patients return for additional surgeries to remove all of the cancer. Post-operative pathology is the gold standard for evaluating BCS margins but is limited due to the amount of tissue that can be sampled. Frozen section analysis and touch-preparation cytology have been proposed to address the surgical needs but also have sampling limitations. These issues represent an unmet clinical need for guidance in resecting malignant tissue intra-operatively and for pathological sampling. We have developed a quantitative spectral imaging device to examine margins intra-operatively. The context in which this technology is applied (intra-operative or post-operative setting) is influenced by time after excision and surgical factors including cautery and the presence of patent blue dye (specifically Lymphazurin™, used for sentinel lymph node mapping). Optical endpoints of hemoglobin ([THb]), fat ([β-carotene]), and fibroglandular content via light scattering (<µs’>) measurements were quantified from diffuse reflectance spectra of lumpectomy and mastectomy specimens using a Monte Carlo model. A linear longitudinal mixed-effects model was used to fit the optical endpoints for the cautery and kinetics studies. Monte Carlo simulations and tissue mimicking phantoms were used for the patent blue dye experiments. [THb], [β-carotene], and <µs’> were affected by <3.3% error with <80 µM of patent blue dye. The percent change in [β-carotene], <µs’>, and [β-carotene]/<µs’> was <14% in 30 minutes, while percent change in [THb] was >40%. [β-carotene] and [β-carotene]/<µs’> were the only parameters not affected by cautery. This work demonstrates the importance of understanding the post-excision kinetics of ex-vivo tissue and the presence of cautery and patent blue dye for breast tumor margin assessment, to accurately interpret data and exploit underling sources of contrast.
PMCID: PMC3519619  PMID: 23251526
8.  Systems Biology from a Yeast Omics Perspective 
Febs Letters  2009;583(24):3895-3899.
Systems biology represents a paradigm shift from the study of individual genes, proteins or other components to that of the analysis of entire pathways, cellular, developmental, or organismal processes. Large scale studies, primarily initiated in S. cerevisiae, have allowed the identification and characterization of components on an unprecedented level. Large scale interaction, transcription factor binding and phosphorylation data have enabled the elucidation of global regulatory networks. These studies have helped provide an understanding of cellular pathways and processes at a global and systems level.
PMCID: PMC3262145  PMID: 19903479
Systems biology; genomics; proteomics; transcriptome; phosphorylome; S.cerevisiae
9.  The graduate entry generation: a qualitative study exploring the factors influencing the career expectations and aspirations of a graduating cohort of graduate entry dental students in one London institution 
BMC Oral Health  2011;11:25.
Dentistry in the UK has a number of new graduate-entry programmes. The aim of the study was to explore the motivation, career expectations and experiences of final year students who chose to pursue a dental career through the graduate entry programme route in one institution; and to explore if, and how, their intended career expectations and aspirations were informed by this choice.
In-depth interviews of 14 graduate entry students in their final year of study. Data were transcribed verbatim and analysed using framework analysis.
There were three categories of factors influencing students' choice to study dentistry through graduate entry: 'push', 'pull' and 'mediating'. Mediating factors related to students' personal concerns and circumstances, whereas push and pull factors related to features of their previous and future careers and wider social factors. Routes to Graduate Entry study comprised: 'early career changers', 'established career changers' and those pursuing 'routes to specialisation'. These routes also influenced the students' practice of dentistry, as students integrated skills in their dental studies, and encountered new challenges.
Factors which students believed would influence their future careers included: vocational training; opportunities for specialisation or developing special interests and policy-related issues, together with wider professional and social concerns.
The graduate entry programme was considered 'hard work' but a quick route to a professional career which had much to offer. Students' felt more could have been made of their pre-dental studies and/or experience during the programme. Factors perceived as influencing students' future contribution to dentistry included personal and social influences. Overall there was strong support for the values of the NHS and 'giving back' to the system in their future career.
Graduate entry students appear to be motivated to enter dentistry by a range of factors which suit their preferences and circumstances. They generally embrace the programme enthusiastically and seek to serve within healthcare, largely in the public sector. These students, who carry wider responsibilities, bring knowledge, skills and experience to dentistry which could be harnessed further during the programme. The findings suggest that graduate entry students, facilitated by varied career options, will contribute to an engaged workforce.
PMCID: PMC3201891  PMID: 21942994
dental; graduate; graduate-entry; career; motivation; workforce
10.  Insights into the oral health beliefs and practices of mothers from a north London Orthodox Jewish community 
BMC Oral Health  2010;10:14.
The objective of this study was to explore oral health knowledge and beliefs and access to dental care in a culturally distinct Orthodox Jewish community in North London, with a view to informing local health policy.
A dual method qualitative approach to data collection was adopted in this study utilising semi-structured face to face interviews and focus groups with women from this North London orthodox Jewish community. In total nine interviews and four focus groups were conducted with a purposive sample of thirty three mothers from the community aged 21-58 years. The data were transcribed and analysed using Framework Methodology
Cultural influences, competing pressures and perceptions of hereditary influences, together with a lack of contemporary oral health knowledge are the main factors affecting oral health knowledge and beliefs. This supported an overall perspective of disempowerment or a perceived lack of control over oral health behaviours, both for mothers and their children. Community signposting pointed mothers to dental services, whilst family pressures together with inadequate capacity and capability and generic barriers such as fear and cost acted as barriers. Mothers from this community welcomed community development initiatives from the NHS.
The results of this study provide insight into the challenges of a culturally isolated community who would welcome community support through schools and expanded culturally appropriate opening hours to improve access to dental care.
PMCID: PMC2894741  PMID: 20529247
11.  The emerging dental workforce: long-term career expectations and influences. A quantitative study of final year dental students' views on their long-term career from one London Dental School 
BMC Oral Health  2009;9:35.
Research into the motivation and expectations of the emerging workforce and their short-term expectations has already been reported with a view to informing professional and policy decisions. The objective of this component of the research programme was to examine the long-term goals and perceived influences on final year dental students' professional careers.
Univariate analysis of a self completed questionnaire survey of all final year dental students from King's College London, comprising questions on demography, long-term career goals and influences, proposed commitment to dentistry, commitment to healthcare systems and the influences thereon. Statistical analysis included Chi Squared tests for linear association.
Ninety per cent of students responded to this survey (n = 126), the majority of whom were aged 23 years (59%), female (58%) and Asian (70%). Long-term career goals were fairly evenly split between 'dentist with a special interest' (27%), 'primary dental care practitioner' (26%) and 'specialist' (25%), with 19% not certain. Only 60% of total respondents anticipated working full-time in the long-term (79% males cf 52% females; p = 0.00). The vast majority of respondents (≥80%) identified 'work-life balance', 'financial stability' and 'professional development' as 'important' or 'very important' influences on the number of future sessions. Females were significantly more likely to rate childcare commitments as an important influence on their future working capacity compared with males (p = 0.00). A wide range of factors were considered important or very important in making the NHS attractive, led by support for professional development (88%) and feeling valued by patients (88%), as well as funding, time with patients, rewards for prevention and practical issues such as dental materials and premises. Females were significantly more likely than males to be attracted to work within the NHS by 'childcare support' (p = 0.02), 'retraining facilities after career break' (p = 0.01), 'assistance with student debt' (p = 0.01) and 'incentives to work in deprived areas'.
Long-term career plans of new graduates from this London Dental School commonly embrace opportunities for professional development as well as personal issues such as work/life balance and financial income. Significant differences were identified between male and females long-term plans and influences. The implications of these findings are discussed.
PMCID: PMC2814807  PMID: 20030814
12.  Use of the out-of-hours emergency dental service at two south-east London hospitals 
BMC Oral Health  2009;9:19.
Prior to the introduction of the 2006 NHS dental contract in England and Wales, general dental practitioners (GDPs) were responsible for the provision of out-of-hours (OOH) emergency dental services (EDS); however there was great national variation in service provision. Under the contractual arrangements introduced 1st April 2006, local commissioning agencies became formally responsible for the provision of out-of-hours emergency dental services. This study aimed to examine patients' use of an out-of-hours emergency dental service and to determine whether the introduction of the 2006 national NHS dental contract had resulted in a change in service use, with a view to informing future planning and commissioning of care.
A questionnaire was administered to people attending the out-of-hours emergency dental service at two inner city London hospitals over two time periods; four weeks before and six months after the introduction of the dental contract in April 2006. The questionnaire explored: reasons for attending; dental registration status and attendance; method of access; knowledge and use of NHS Direct; satisfaction with the service; future preferences for access and use of out-of-hours dental services. Data were compared to determine any impact of the new contract on how and why people accessed the emergency dental service.
The response rate was 73% of attendees with 981 respondents for the first time period and 546 for the second. There were no significant differences between the two time periods in the gender, age, ethnic distribution or main language of service users accessing the service. Overall, the main dental problem was toothache (72%) and the main reason for choosing this service was due to the inability to access another emergency dental service (42%). Significantly fewer service users attended the out-of-hours emergency dental service during the second period because they could not get an appointment with their own dentist (p = 0.002 from 28% to 20%) and significantly more service users in the second period felt the emergency dental service was easier to get to than their own dentist (P = 0.003 from 8% to 14%). Service users found out about the service from multiple sources, of which family and friends were the most common source (30%). In the second period fewer service users were obtaining information about the service from dental receptionists (P = 0.002 from 14% to 9%) and increased use of NHS Direct for a dental problem was reported (P = 0.002 from 16% to 22%) along with more service users being referred to the service by NHS Direct (P = 0.02 from 19% to 24%). The most common preference for future emergency dental care was face-to-face with a dentist (79%).
This study has provided an insight into how and why people use an out-of-hours emergency dental service and has helped to guide future commissioning of these services. Overall, the service was being used in much the same way both before and after the 2006 dental contract. Significantly more use was being made of NHS Direct after April 2006; however, informal information networks such as friends and family remain an important source of information about accessing emergency dental services.
PMCID: PMC2729730  PMID: 19630986
13.  Minimising barriers to dental care in older people 
BMC Oral Health  2008;8:7.
Older people are increasingly retaining their natural teeth but at higher risk of oral disease with resultant impact on their quality of life. Socially deprived people are more at risk of oral disease and yet less likely to take up care. Health organisations in England and Wales are exploring new ways to commission and provide dental care services in general and for vulnerable groups in particular. This study was undertaken to investigate barriers to dental care perceived by older people in socially deprived inner city area where uptake of care was low and identify methods for minimising barriers in older people in support of oral health.
A qualitative dual-methodological approach, utilising both focus groups and individual interviews, was used in this research. Participants, older people and carers of older people, were recruited using purposive sampling through day centres and community groups in the inner city boroughs of Lambeth, Southwark and Lewisham in South London. A topic guide was utilised to guide qualitative data collection. Informants' views were recorded on tape and in field notes. The data were transcribed and analysed using Framework Methodology.
Thirty-nine older people and/or their carers participated in focus groups. Active barriers to dental care in older people fell into five main categories: cost, fear, availability, accessibility and characteristics of the dentist. Lack of perception of a need for dental care was a common 'passive barrier' amongst denture wearers in particular. The cost of dental treatment, fear of care and perceived availability of dental services emerged to influence significantly dental attendance. Minimising barriers involves three levels of action to be taken: individual actions (such as persistence in finding available care following identification of need), system changes (including reducing costs, improving information, ensuring appropriate timing and location of care, and good patient management) and societal issues (such as reducing isolation and loneliness). Older people appeared to place greater significance on system and societal change than personal action.
Older people living within the community in an inner city area where NHS dental care is available face barriers to dental care. Improving access to care involves actions at individual, societal and system level. The latter includes appropriate management of older people by clinicians, policy change to address NHS charges; consideration of when, where and how dental care is provided; and clear information for older people and their carers on available local dental services, dental charges and care pathways.
PMCID: PMC2335092  PMID: 18366785
14.  Dentistry – a professional contained career in healthcare. A qualitative study of Vocational Dental Practitioners' professional expectations 
BMC Oral Health  2007;7:16.
New graduates in the UK presently spend one year in training as Vocational Dental Practitioners (VDPs) in preparation for primary dental care. There is a growing recognition that the emerging workforce has very different professional expectations to those of earlier generations, with implications for the profession, patients and the performance of health systems. The objectives of this study were to investigate why VDPs' in England and Wales perceive they chose dentistry as a professional career; how they perceive their vision has changed and the implications for their professional career plans, both short- and longterm.
Purposive sampling of schemes was undertaken to include urban, rural and metropolitan schemes, schemes in areas with and without dental schools and geographic coverage across England and Wales. All VDPs in these schemes were initiated to participate in this qualitative study using focus groups. A topic guide was utilised to standardise data collection. Informants' views were recorded on tape and in field notes. Data were transcribed and analysed using Framework Methodology.
A total of 99 VDPs participated in the 10 focus groups. Their choice of dentistry as a professional career was motivated by multiple categories of influence: 'academic', 'healthcare', 'lifestyle', the influence of 'family', 'friends', 'careers advice' and 'work experience'. Consideration of the features of the 'professional job' appears to have been key to their choice of dentistry and the 'active rejection of medicine' as an alternative career.
Entry into the profession was proving a challenging process for some but not all VDPs. Informants perceived that their vision had been moderated as a result of 'personal student debt', 'national workforce initiatives', 'limitations on clinical practice' and the 'cost of additional training'.
Short term goals focused around 'recovery from the past' and 'preparation for the future'. Longterm goals covered the spectrum of opportunities within dentistry. Factors influencing VDPs longterm career plans fell into six main categories: professional, personal, financial, political, social and cultural.
VDPs chose dentistry because they perceived that it provides a financially lucrative, contained career in healthcare, with professional status, job security and the opportunity to work flexibly. They perceive that their vision is challenged by changes affecting education and the healthcare system. Longterm professional expectations were closely linked with their personal lives and support a vision of a favourable work/life balance.
PMCID: PMC2200640  PMID: 18005452
15.  The emerging dental workforce: why dentistry? A quantitative study of final year dental students' views on their professional career 
BMC Oral Health  2007;7:7.
Dental graduates are joining a profession experiencing changes in systems of care, funding and skill mix. Research into the motivation and expectations of the emerging workforce is vital to inform professional and policy decisions. The objective of this research was to investigate final year dental students' perceived motivation for their choice of career in relation to sex, ethnicity and mode of entry.
Self-administered questionnaire survey of all final year dental students at King's College London. Data were entered into SPSS; statistical analysis included Chi Squared tests for linear association, multiple regression, factor analysis and logistic regression.
A response of 90% (n = 126) was achieved. The majority were aged 23 years (59%), female (58%) and Asian (70%). One in 10 were mature students. Eighty per cent identified 11 or more 'important' or 'very important' influences, the most common of which were related to features of the job: 'regular working hours' (91%), 'degree leading to recognised job' (90%) and 'job security' (90%). There were significant differences in important influences by sex (males > females: 'able to run own business'; females > males: 'a desire to work with people'), ethnic group (Asians > white: 'wish to provide public service', 'influence of friends', 'desire to work in healthcare', having 'tried an alternative career/course' and 'work experience') and mode of entry (mature > early entry: 'a desire to work with people'). Multivariate analysis suggested 61% of the variation in influences is explained by five factors: the 'professional job' (31%), 'healthcare-people' (11%), 'academic-scientific' (8%), 'careers-advising' (6%), and 'family/friends' (6%). The single major influence on choice of career was a 'desire to work with people'; Indian students were twice as likely to report this as white or other ethnic groups.
Final year dental students report a wide range of important influences on their choice of dentistry, with variation by sex, ethnicity and mode of entry in relation to individual influences. Features of the 'professional job', followed by 'healthcare and people' were the most important underlying factors influencing choice of career.
PMCID: PMC1929066  PMID: 17573967
16.  The Small-Subunit Processome Is a Ribosome Assembly Intermediate 
Eukaryotic Cell  2004;3(6):1619-1626.
The small-subunit (SSU) processome is a large ribonucleoprotein required for the biogenesis of the 18S rRNA and likely corresponds to the terminal knobs visualized by electron microscopy on the 5′ end of nascent rRNAs. The original purification of the SSU processome of Saccharomyces cerevisiae resulted in the identification of 28 proteins. Here, we characterize 12 additional protein components, including five small-ribosomal-subunit proteins (Rps4, Rps6, Rps7, Rps9, and Rps14) that had previously been copurified. Our multiple criteria for including a component as a bona fide SSU processome component included coimmunoprecipitation with Mpp10 (an SSU processome component), the U3 snoRNA, and the anticipated pre-rRNAs. Importantly, the association of specific ribosomal proteins with the SSU processome suggests that the SSU processome has roles in both pre-rRNA processing and ribosome assembly. These ribosomal proteins may be analogous to the primary or secondary RNA binding proteins first described in bacterial in vitro ribosome assembly maps. In addition to the ribosomal proteins and based on the same experimental approach, we found seven other proteins (Utp18, Noc4, Utp20, Utp21, Utp22, Emg1, and Krr1) to be bona fide SSU processome proteins.
PMCID: PMC539036  PMID: 15590835
17.  Two-hybrid Mpp10p interaction-defective Imp4 proteins are not interaction defective in vivo but do confer specific pre-rRNA processing defects in Saccharomyces cerevisiae 
Nucleic Acids Research  2004;32(4):1404-1413.
The SSU processome is a large, evolutionarily conserved ribonucleoprotein (RNP), consisting of the U3 snoRNA and at least 28 protein components, that is required for biogenesis of the 18S rRNA. We tested the function of one protein–protein interaction in the SSU processome, Mpp10p–Imp4p, in ribosome biogenesis. Exploiting the reverse two-hybrid system, we screened for mutated Imp4 proteins that were conditionally defective for interaction with Mpp10p. Three different imp4 sequences were isolated that: (i) conferred conditional growth in the two-hybrid strain; (ii) complemented the disrupted imp4; (iii) conferred conditional growth in the context of their normal cellular function; and (iv) resulted in defective pre-rRNA processing at the non-permissive temperatures. Domain swapping revealed that mutations that conferred cold sensitivity resided in the N-terminal coiled-coil domain while mutations in the C-terminus conferred temperature sensitivity. Surprisingly, the mutated Imp4 proteins were not measurably defective for interaction with Mpp10p in the context of the SSU processome. This suggests that other members of the complex may contribute to maintaining the Mpp10p–Imp4p interaction in this large RNP. Since protein–protein interactions are critical for many different aspects of cellular metabolism, our work has implications for the study of other large protein complexes.
PMCID: PMC390303  PMID: 14990745
18.  The human Imp3 and Imp4 proteins form a ternary complex with hMpp10, which only interacts with the U3 snoRNA in 60–80S ribonucleoprotein complexes 
Nucleic Acids Research  2003;31(7):1877-1887.
Ribosome biogenesis requires a vast number of trans-acting factors many of which are required for the chemical modification and processing of the pre-rRNA component. The U3 snoRNP complex is required for the early cleavage steps in pre-rRNA processing. We have cloned cDNAs encoding the human and mouse homologs of the yeast U3 snoRNP-associated proteins Imp3 and Imp4. Both human proteins localize to nucleoli and interact with the U3 snoRNA. The results of complementation experiments show that, in contrast to mouse Imp4, mouse Imp3 can partially alleviate the growth defect of the corresponding yeast null strain, indicating that the role of Imp3 in pre-rRNA processing is evolutionarily conserved. The results of density gradient centrifugation experiments show that, in contrast to hU3-55K, the human Imp3 and Imp4 proteins predominantly interact with the U3 snoRNA in 60–80S ribonucleoprotein complexes. In addition, we have found that hImp3, hImp4 and hMpp10 can form a stable hetero-trimeric complex in vitro, which is generated by direct interactions of both hImp3 and hImp4 with hMpp10. The analysis of hImp3 and hImp4 mutants indicated that their binding to hMpp10 correlates with their nucleolar accumulation, strongly suggesting that the formation of the ternary complex of hImp3, hImp4 and hMpp10 is required for their association with nucleolar components.
PMCID: PMC152815  PMID: 12655004
19.  Delayed rRNA Processing Results in Significant Ribosome Biogenesis and Functional Defects 
Molecular and Cellular Biology  2003;23(5):1602-1613.
mof6-1 was originally isolated as a recessive mutation in Saccharomyces cerevisiae which promoted increased efficiencies of programmed −1 ribosomal frameshifting and rendered cells unable to maintain the killer virus. Here, we demonstrate that mof6-1 is a unique allele of the histone deacetylase RPD3, that the deacetylase function of Rpd3p is required for controlling wild-type levels of frameshifting and virus maintenance, and that the closest human homolog can fully complement these defects. Loss of the Rpd3p-associated histone deacetylase function, either by mutants of rpd3 or loss of the associated gene product Sin3p or Sap30p, results in a delay in rRNA processing rather than in an rRNA transcriptional defect. This results in production of ribosomes having lower affinities for aminoacyl-tRNA and diminished peptidyltransferase activities. We hypothesize that decreased rates of peptidyl transfer allow ribosomes with both A and P sites occupied by tRNAs to pause for longer periods of time at −1 frameshift signals, promoting increased programmed −1 ribosomal frameshifting efficiencies and subsequent loss of the killer virus. The frameshifting defect is accentuated when the demand for ribosomes is highest, suggesting that rRNA posttranscriptional modification is the bottleneck in ribosome biogenesis.
PMCID: PMC151716  PMID: 12588980
20.  Components of an Interdependent Unit within the SSU Processome Regulate and Mediate Its Activity 
Molecular and Cellular Biology  2002;22(20):7258-7267.
The SSU processome is required for production of the small ribosomal subunit RNA, the 18S rRNA. Specifically, the U3 small nucleolar RNA (snoRNA) component of the SSU processome is essential for the formation of the conserved central pseudoknot and for cleavages of the pre-rRNA, both of which are required for 18S maturation. To further elucidate how these events are mediated, we examined the regulatory and mechanistic roles of the U3 specific proteins: Imp3p, Imp4p, and Mpp10p. We found that these proteins demonstrated an interdependence with respect to their stability and to their association with the U3 snoRNA. Because mutations in the U3 snoRNA that disrupt pre-rRNA processing confer similar defects on growth and pre-rRNA processing as do carboxy-terminal truncations of Mpp10p, we hypothesized that Mpp10p may be involved in maintaining U3 snoRNA-pre-rRNA base pairing. However, combining the two mutations resulted in a more pronounced cleavage defect at site A2, suggesting that Mpp10p is also required at an additional mechanistic step. Furthermore, heterologous complementation experiments demonstrate that the last 95 amino acids of yeast Mpp10p are specifically required for growth and pre-rRNA processing at low temperatures.
PMCID: PMC139808  PMID: 12242301

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