Solitary

This novella explores the themes of isolation and captivity. Millie Canfield feels isolated and held captive by her family. She dreams of freedom and beauty, only to see her attempts to achieve it repeatedly undone. She flees from family to marriage, only to experience isolation and captivity in a different form. She wants to be rescued, but she is oblivious to outside attempts to help. Millie also holds herself captive, torn between her perceived wants and obligations. She feels isolated, but she has isolated herself. When she at last achieves a measure of freedom, it is more a case of outlasting her prison than of actually escaping

Design of, and first data from, PATRO Children, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope in children requiring growth hormone treatment

Objective: To describe the rationale, design and first data from PATRO Children, a postmarketing surveillance of the long-term efficacy and safety of somatropin (Omnitrope ® ) for the treatment of children requiring growth hormone treatment. Methods: PATRO Children is a multicentre, open, longitudinal, noninterventional study being conducted in children’s hospitals and specialised endocrinology clinics. The primary objective is to assess the long-term safety of Omnitrope ® in routine clinical practice. Eligible patients are infants, children and adolescents (male or female) who are receiving treatment with Omnitrope ® and who have provided informed consent. Patients who have been treated with another recombinant human growth hormone (rhGH) product before starting Omnitrope ® are eligible for inclusion. All adverse events (AEs) are monitored and recorded, with particular emphasis on: long-term safety; the recording of malignancies; the occurrence and clinical impact of anti-hGH antibodies; the development of diabetes during Omnitrope ® treatment in children short for gestational age (SGA); safety issues in patients with Prader–Willi syndrome (PWS). Efficacy assessments include auxological parameters, plus insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Results: As of September 2012, 1837 patients were enrolled in the study from 184 sites in 10 European countries. To date, efficacy data are reassuring and consistent with previous studies. In addition, there have been no confirmed cases of diabetes occurring under Omnitrope ® treatment, no reports of malignancy and no safety issues in PWS patients. Conclusions: The efficacy and safety profile of Omnitrope ® in the PATRO Children study so far are as expected. The ongoing study will extend the safety database for Omnitrope ® , and rhGH products more generally, in paediatric indications. Of particular interest, PATRO Children will add important information on the diabetogenic potential of rhGH in children born SGA, the risk of malignancies in children receiving rhGH, and AEs with a possible causal relationship to rhGH treatment in children with PWS

Identification of Human T-Cell Responses to Mycobacterium tuberculosis Resuscitation-Promoting Factors in Long-Term Latently Infected Individuals ▿ †

The Mycobacterium bovis BCG vaccine is the only tuberculosis (TB) vaccine available, yet it provides limited protection against pulmonary TB in adults and fails to protect against TB reactivation. We hypothesized that immunity against Mycobacterium tuberculosis “resuscitation-promoting factors” (Rpfs), which are small bacterial proteins that promote proliferation of dormant mycobacteria, may be relevant in the human immune response to M. tuberculosis. In previous unpublished work, we found that Rpfs Rv0867c and Rv2389c induced gamma interferon (IFN-γ) production in the blood of TB patients' healthy household contacts in several different African populations. Here we examine these two dominant Rpf antigens in more detail and define the nature of the responding T-cell subsets. Multiparameter cytokine profiling showed that Rv2389c and, to a lesser extent, Rv0867c were recognized by mycobacterium-responsive healthy Dutch individuals; peptide-scanning revealed several epitopes, including a single immunodominant epitope in Rv2389c. Rv0867c and, to a lesser extent, Rv2389c Rpf-specific T-cell responses were maintained for decades in long-term M. tuberculosis nonprogressors. Prominent Rv0867c-specific double- and single-cytokine-producing CD8+ T-cell subset responses were found, including a large population of CD8+ effector memory and effector T-cell subsets. We conclude that M. tuberculosis Rpf antigens are important targets in the human immune response to M. tuberculosis and represent interesting TB vaccine candidate antigens