An important consideration when expressing mAbs in Escherichiacoli.

Monoclonal antibodies (mAbs) are a driving force in the biopharmaceutical industry. Therapeutic mAbs are usually produced in mammalian cells, but there has been a push towards the use of alternative production hosts, such as Escherichia coli. When the genes encoding for a mAb heavy and light chains are codon-optimized for E. coli expression, a truncated form of the heavy chain can form along with the full-length product. In this work, the role of codon optimization in the formation of a truncated product was investigated. This study used the amino acid sequences of several therapeutic mAbs and multiple optimization algorithms. It was found that several algorithms incorporate sequences that lead to a truncated product. Approaches to avoid this truncated form are discussed.

Factors associated with failed 'test of cure' in the NHS Cervical Screening Programme: A retrospective cohort study.

OBJECTIVE: To determine predictive factors associated with failed 'test of cure' (TOC) in the NHS Cervical Screening Programme (NHSCSP). METHODS: Retrospective cohort study of all patients treated by large loop excision of transformation zone (LLETZ) between 1st April 2014 and 1st April 2019. Those with no documented HPV genotype on referral, no TOC outcome, those having a hysterectomy, chemotherapy and/or radiotherapy were excluded from final analysis. RESULTS: Patients referred with a singular HPV genotype of HPV 16, HPV 18, or HPV Other types (HPV O) were significantly more likely to pass TOC than those referred with multiple HPV genotypes (p < 0.0001). Those with HPV genotypes including HPV O were significantly more likely to fail TOC as compared to those with genotypes of solely HPV 16 and/or 18 (p < 0.0001). Patients aged ≥51 years were significantly more likely to fail TOC when compared to all other age groups (p < 0.0001). CONCLUSION: Age >51 yrs. and infection with multiple hr-HPV types were predictors of post treatment hr-HPV persistence. Knowledge of HPV genotype both at referral, and following treatment, could allow a more individualised, and patient-centred, approach to both the management and follow up of CIN. HPV genotype should be reported as standard on all cervical screening sample results. The term HPV O should not be utilised and instead actual HPV genotype should be reported. This would enable us to optimise not only future research but would also allow future monitoring of the efficacy of vaccination programmes.

Clinical indications referrals - what is the risk of premalignant and malignant female genital tract disease in women referred to a dedicated nurse-led colposcopy service? A retrospective cohort study.

Post-coital bleeding (PCB) is a poor predictive factor for cancer and should not be managed as urgent referral. Urgent referral to colposcopy is justified however, in the presence of a visible suspicion of cervical cancer. This retrospective cohort study of women attending a clinical indications referral service aims to identify the risk of pre-malignant and malignant disease in women with clinical indication referrals to colposcopy. Thirty-seven of 3521 women (1%) were diagnosed with pre-malignant cervical or endometrial disease; 14 women (0.4%) were diagnosed with cancer (11 cervix, three endometrial). To detect one cancer in women referred with an abnormal cervix, one would need to see 70 women; to detect one cancer in women referred with PCB one would need to see 790 women. Improved education in primary care and obstetrics and gynaecology training is key to improving clinical indications referral services, which is otherwise an effective and efficient service.Impact StatementWhat is already known on this subject? Post-coital bleeding is a poor predictive factor for cancer and should not be considered an urgent referral.What do the results of this study add? The presence of a visible suspicion of cervical cancer however does warrant urgent referral as approximately one in 70 women will have a malignancy detected.What are the implications of these findings for clinical practice and/or further research? Improved education in primary care and obstetrics and gynaecology training is the key to improving clinical indications referral services.

Are we managing our patients correctly following treatment for cervical glandular intraepithelial neoplasia? A review of practice at the Jessop Wing Colposcopy Unit.

OBJECTIVE: Women diagnosed with cervical glandular intraepithelial neoplasia (CGIN) remain at risk of further pre-malignant and malignant disease and require rigorous post-treatment follow-up. We assess the effectiveness and safety of community cervical sampling follow-up in women treated for CGIN. METHODS: A retrospective study was conducted of women diagnosed with CGIN between April 1, 2013, and March 31, 2019, at Jessop Wing Colposcopy Unit, Sheffield, UK. RESULTS: Of 140 women diagnosed with CGIN, 76 had co-existing cervical intraepithelial neoplasia (CIN). Cytologists were significantly more likely to report glandular neoplasia in the absence of co-existing CIN, and high-grade dyskaryosis in its presence (Ps < 0.0001). Co-existing CIN was significantly more likely to be present with high or low-grade compared to normal colposcopy findings (P < 0.0001). The 6-month test of cure (TOC) was attended by 67% of women (84% within 12 months), and the 18-month post-treatment sampling by 52.5% of women (70% within 24 months). Colposcopy recalled 96% of women correctly for the 18-month sampling, but 20% of women undertaking primary care samples were incorrectly recalled at 3 years instead. CONCLUSIONS: When CGIN is diagnosed, two dates for recall should be provided at 6 and 18 months post-treatment to the Cervical Screening Administration Service and the centralised screening laboratory ensuring the 18-month post-treatment sample is correctly appointed, preventing women with HPV-negative TOC samples being returned to 3-year recall. Follow-up of CGIN should be closely audited by the centralised laboratories ensuring women with CGIN are not put at additional risk.

Dreaming of you: client and therapist dreams about each other during psychodynamic psychotherapy.

OBJECTIVES: Our objectives were to describe the frequency of therapists' dreams about their clients and clients' dreams about their therapists, to determine how therapists and clients who had such dreams differed from those who did not have such dreams, whether therapy process and outcome differed for those who had and did not have such dreams, and to describe the content and consequences of these dreams. METHODS: Thirteen doctoral student therapists conducted psychodynamic psychotherapy with 63 clients in a community clinic. RESULTS: Therapists who had dreams about clients had higher estimated and actual dream recall than did therapists who did not dream about clients. Qualitative analyses indicated that therapists' dreams yielded insights about the therapist, clients, and therapy; therapists used insights in their work with the clients. Among the clients, only two (who were particularly high in attachment anxiety and who feared abandonment from their therapists) reported dreams that were manifestly about their therapists. CONCLUSIONS: Therapists-in-training dreamed more about their clients than their clients dreamed about them. Dreams about clients can be used by therapists to understand themselves, clients, and the dynamics of the therapy relationship.

Clients' perspectives on therapy termination.

We used consensual qualitative research to analyze interviews with 12 clients about their termination from psychotherapy. Those who had positive termination experiences reported a strong therapeutic relationship and positive outcomes of therapy. They terminated primarily for logistical or financial reasons; their termination, post-termination plans, and feelings about termination were discussed in advance with their therapist, as was their growth in therapy, leading to mostly positive effects of the termination. In contrast, those who had problematic terminations reported a mixed therapeutic relationship and mixed outcomes of therapy. They usually terminated abruptly because of a therapeutic rupture, and thus termination was rarely planned and discussed in advance, rendering it a negative experience. Implications of these findings are addressed.

Therapist training, feedback, and practice for dream work: a pilot study.

Thirteen therapists (8 women, 5 men; M age = 29.1 yr., SD = 6.3; M counseling experience 2.7 yr., SD = 6.3, range = 1 semester to 8 yr.) received training in the cognitive-experiential model of dream work through a didactic-experiential workshop, individual feedback, and practice. All participants but one were enrolled in masters' or doctoral level counseling training programs. An examination of effect sizes indicated that (a) therapists' self-efficacy about using the dream model increased substantially and positive attitudes toward dreams increased slightly after the didactic-experiential workshop; (b) the process and outcome of the second dream session were better for therapists who received individual feedback after the first session than for therapists who did not receive feedback after the first session; and (c) for the subgroup of six therapists who conducted five sessions, therapists' attitudes toward using the dream model improved, and their self-efficacy for working with dreams and perceived self-competence in dream work increased.

Case studies of the attainment of insight in dream sessions: replication and extension.

To replicate and extend the Hill, Knox, et al. (2007) case study of a client who attained insight in one session of dream work, the authors examined two additional single-session cases: one in which a client gained insight and another in which a client did not. The observations across all three cases suggest that the two clients who acquired insight had positive attitudes toward dreams; were motivated and involved in session; and were nonresistant, trusting, and affectively present but not overwhelmed. The client who did not gain insight questioned the value of dreams and was resistant, untrusting, and emotionally overwhelmed. Therapist adherence and competence using the dream model, ability to manage countertransference, and effective use of probes for insight distinguished the therapists whose clients gained insight from the therapist whose client did not.

Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I, particularly in non-HPV 16 patients.

OBJECTIVE: To assess the influence of high-risk Human Papilloma Virus (hrHPV) genotyping on the detection of high-grade disease (CIN2+) using colposcopic impression both with and without electrical impedance spectroscopy (ZedScan I) as an adjunct. STUDY DESIGN: A prospective cohort of women with a known hrHPV genotype referred to a single colposcopy service. RESULTS: 839 women underwent colposcopy and ZedScan I examination. 613 women were referred with abnormal cytology; 411 (67%) with low-grade dyskaryosis (67%) and 202 (33%) with high-grade dyskaryosis. 187 were referred with persistent hrHPV but negative cytology. 35 were attended for follow up and 4 for a clinical indication. 159 (19%) women were positive for HPV16 only; 54 (6%) with HPV18 only, 443 (53%) women were positive for hrHPV other types (HPV O). 183 (22%) were positive for multiple hrHPV genotypes. CIN2+ was present in 170 (84.2%) of high-grade and 69 (16.7%) of low-grade cytology referrals. Colposcopy was better at detecting HPV16 associated CIN2+ than that associated with HPV18 or HPV O (86.9% vs 79.7%, p=0.0191). ZedScan I increased the detection of CIN2+ from 85.6% to 96% irrespective of hrHPV genotype status (p<0.0001). CONCLUSION: The use of an electrical impedance spectroscopic device (ZedScan I) increases detection of CIN2+ irrespective of hrHPV genotype.