Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Q: Context: Complications after immediate breast reconstruction pose a significant challenge to the reconstructive surgeon. Known risk factors include smoking, obesity, age, and adjuvant oncologic therapies. Less is known about the association between axillary lymph node dissection (ALND) and the development of postoperative complications.', 'We conducted a retrospective study of all patients who underwent immediate breast reconstruction after mastectomy at our institution over a 10-year period. Our outcome was an occurrence of a major complication within 90 days postoperatively. For each patient, we recorded data on demographics, smoking status, pertinent medical history, reconstruction type, adjuvant chemotherapy and radiation, tumor pathology, and whether an ALND was performed. Odds ratios (OR) were calculated to estimate the risk of a complication if an ALND was performed.', 'One hundred eighty-four women, with 270 surgically treated breasts, were identified as having mastectomy with immediate reconstruction between 2002 and 2012. Mean age was 49.4 years (range, 25-84 years). There were 71 mastectomies with ALND performed, with 22 complications, and 199 mastectomies without ALND, with 20 complications (31% complication rate vs 10%, respectively; OR, 3.84; P < 0.001). When adjusted for reconstruction type, smoking history, obesity, age, presence of invasive disease, chemotherapy, and radiation therapy, the OR for complications was 3.49 (P < 0.01). The most common complication was infection in both groups.
Answer: Mastectomy with ALND is associated with a 3-fold increase in risk of major complications in women undergoing immediate breast reconstruction, even after adjustment for known risk factors and confounders. Further studies are warranted to elucidate how ALND leads to these complications and what measures can reduce their occurrence.

A: Does axillary Lymph Node Dissection be a Risk Factor for Major Complications After Immediate Breast Reconstruction?
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Q: Context: Critical size defects (CSDs) of bone are defined as defects that do not heal spontaneously to new bone during the lifetime of an adult individual. In contrast, immature animals are capable to heal defects of identical size. It was our hypothesis that age-related paracrine effects are relevant for this difference in regeneration.', 'The pooled supernatant of primary rat calvarial osteoblast-like cell cultures (POBC) derived from prenatal or postnatal donors was concentrated and applied into CSDs of adult recipient organisms (n = 10). In addition, the supernatant of POBC derived from prenatal donors was pooled and purified by reverse-phase chromatography. Each pre-purified fraction was tested in a proliferation indicating bioassay. Peptide fractions containing proliferative activities were re-chromatographed and re-tested in a bioassay. Finally, a proliferative activity was purified, identified by sequence analysis and applied into CSDs of adult recipients.', 'The application of POBC derived from prenatal donors resulted in osseous regeneration of a CSD in adult recipients, while the supernatant of postnatal donors had much smaller effects. The morphologic features resembled the spontaneous osseous healing of calvarial defects of the same size in immature organisms. The polypeptide "tissue inhibitor of metalloproteinases type II"(TIMP-2) was isolated from the supernatant of cultures of POBC derived from prenatal donors by measuring the induction of their proliferation. Additionally, the application of human TIMP-2 injected into calvarial CSDs of adult organisms resulted in osseous healing.
Answer: We conclude that one component responsible for the healing effect of CSDs of POBC supernatants derived from prenatal donors is TIMP-2.

A: Is tissue inhibitor of metalloproteinases II ( TIMP-2 ) an osteoanabolic factor in vitro and in vivo?
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Q: Context: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown.', "Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016).
Answer: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available.

A:
Do low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use?
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